Xarelto Settlement Judicial Activism vs Judicial Tyranny

Xarelto Proposed Settlement 

The death MDL settlements as we know and love them?

 

Foreword: Non leadership firms representing Xarelto plaintiffs facing potential dismissal from orders issued related to the proposed Xarelto settlement might find this article very beneficial.

Although it is still doubtful that the proposed Xarelto settlement will consummate, it appears that Judge Fallon is set to dismiss individual cases for failure to comply with orders arising from the proposed settlement. Such dismissals would arguably be ripe for appeal.

Spoiler Alert: MDL Judges arguably Lack Subject Matter Jurisdiction to issue orders arising from MDL settlements. Any case dismissed for failure to comply with an order issued absent jurisdiction over the subject matter giving rise to the order, would also be a juridical act undertaken without proper jurisdiction. Parties can not wave Subject Matter Jurisdiction, by act nor agreement. There is no time limit to file an appeal related to an order issued in the absence of jurisdiction over the Subject Matter. Orders issued lacking subject matter jurisdiction  are null from the onset and void on their face. Res Judicata does not apply to orders issued in want of jurisdiction over the subject matter.  See Citations of Relevant Law at the end of this article).

The Road to Hell and Good Intentions 

Certain well intended MDL Judges, including Judge Eldon Fallon have subscribed to the theory that “MDLs are Quasi Class Actions” and despite the fact the USC 1407 provides MDL judges with no jurisdiction to participate in MDL settlements, MDL judges could none the less exercised the powers of their court and involved themselves in MDL settlements, reasoning that MDLs are merely Quasi Class Actions. MDL judges ascribing to the “MDLs as Quasi Class Actions” theory have reasoned intra alia that  Federal Judges have jurisdiction over Class Action Settlements and therefore Federal Judges presiding over MDLs (Quasi Class Actions by their  reasoning) have the same jurisdiction as a Federal Judge Presiding over a Class Action, so long as they comply with the requirements of FRCP 23, in particular the requirements of FRCP 23(e) .

MDL Judges willing to arguably overstep their jurisdiction and exercise the power of their courts in MDL settlements, have justified doing so by  simultaneously complying with duties imposed under FRCP 23(e).

FRCP 23(e) requires Federal Judges presiding over Class Actions to conduct fairness hearings and approve any Class Settlement. These fairness hearings are intended in part to provide class action “absent plaintiff parties” protection from would be unscrupulous self-dealing lead class counsel.

Xarelto Settlement Where Activism turned to Tyranny 

Prior to the Xarelto Settlement, all MDL judges who have inserted themselves into MDL settlements have complied with FRCP 23(e) by conducting fairness hearings to allow parties not represented by plaintiffs leadership a voice before imposing any order related to the settlement that might negatively impact any absent plaintiffs case. Judge Fallon conducted extensive fairness hearings in the settlement of the Vioxx litigation. For reasons unknown to the author, Judge Fallon apparently does not view Xarelto plaintiffs as being deserving of the same protections provided Vioxx plaintiffs.

Although Quasi Class Actions do not actually exist, (MDLs are not Quasi Class Actions) and MDL judges arguably have no jurisdiction to involve themselves in MDL settlements, the Judicial Activism undertaken by Quasi Class Actions MDL judges has arguably been beneficial to defendants as well as plaintiffs desiring efficient mass settlement. Neither defendants nor plaintiffs have complained in the past however, Judge Fallon’s failure to conduct fairness hearings related to the proposed Xarelto Settlement may result in an end to the long running gravy train of MDL settlements achieved by activist MDL Judges willing to overstep their jurisdiction to assist parties in effectuating settlement.

In addition to failing to conduct fairness hearings related to the proposed Xarelto settlement, Judge Fallon also appears to be set to dismiss individual plaintiffs’ cases for failure to comply with orders arising from the settlement. These  orders were arguably issued absent jurisdiction over the subject matter. Any future order arising from the settlement orders, including an order dismissing a case for failing to comply with the settlement related orders, would also be issued without jurisdiction over the subject matter.

Appeals arising from the forgoing, may result in the creation of case law that puts an end to MDL judges inserting themselves into MDL settlements, making reaching mass settlement in MDLs a far more difficult task.

It should be noted I (John Ray) hold Judge Fallon in high esteem. I believe Judge Fallon is wise and fair minded. Despite the foregoing, even wise and fair-minded Judges can err.  I do not view Judge Fallon as a tyrant in general however, acts of tyranny are acts of tyranny, without regard to the general character of those that commit the acts.

 

Back Ground

MDL Judges presiding over Class Actions (FRCP 23) not only have jurisdiction over settlement, Judges presiding over Class Actions have a duty to insure than any proposed settlement is fair to all parties including “absent” parties. FRCP 23(e) Requires Judges presiding over Class Actions to conduct fairness hearings, and rule on the fairness of a class action settlement.

Rule 23(e) is the only safeguard provided to absent class members under Rule 23, protecting these vulnerable parties from self-dealing class action lead counsel that might be inclined to act to the common detriment of absent class members vs the common benefit of those absent parties.

Conversely USC 1407, passed by Congress in 1968, formerly codifying Multidistrict Litigation as a means by which very Federal Jurisdiction can be imposed, provided no jurisdiction for MDL judges to oversee, assist in, issue orders related to or arising from, mass settlement. Additionally, USC 1407, having extended no “settlement jurisdiction” to MDL judges also provided no protection from would be self-dealing lead counsel in MDLs that might act to the common detriment of absent plaintiffs (those not represented by leadership firms).

How Can This Be?

Common Misconception: MDL Judges Have Jurisdiction of the Subject Matter as Well as Personal Jurisdiction to oversee or enter orders to assist mass settlement.

Jurisdiction over the Subject Matter: Arguably does not exist!

Personal Jurisdiction: Arguably does not exist, except for cases that arose in the MDL Courts home State and then only if that court would otherwise have jurisdiction.

Wait a Second!

Wait a Second – MDL Judges frequently involve themselves in MDL mass settlements, how do they justify acting in excess of their Jurisdiction? How could the question of these judges jurisdiction over MDL settlement remained unresolved?

No party to an MDL to date,  has been so aggrieved by an MDL Judges overreach on settlement to force higher courts to deal with the issues. The Xarelto settlement is likely to change the foregoing.

 

The Birth of MDLs as Quasi Class Actions

Judge Jack B. Weinstein, presiding over the Zyprexa Litigation (MDL 1596), was the first MDL Judge (that we are aware of) to presume jurisdiction over settlement matters in Multidistrict Litigation under the “MDLs as Quasi Class Actions“ theory.

Weinstein reasoned that MDLs are “Quasi Class Actions” and cited (inter alia), his inherent authority under the “All Writs Act 28 U.S.C 1651” as providing him “inherent authority” over MDL settlements.

Judge Eldon Fallon, while presiding over the Vioxx Litigation, llowing Judge Weinstein’s Quasi Class Actions theory exerted his self-claimed inherent authority to wade into settlement of that litigation. Other MDL Judges (but not all) have also subscribed to Judge Weinstein’s “MDLs as Quasi Class Actions” theory.

Judge Eldon Fallon in Vioxx, as well as other “MDLs as Quasi Class Action  Judges” have reasoned that their involvement in MDL settlements is equitable, so long as the provisions of FRCP 23(e), are observed.  FRCP 23(e) is intended to provide protection from would be self-dealing lead Class Counsel. FRCP 23(e) obligates Federal Judges overseeing Class Actions to conduct fairness hearings (giving absent class members a chance to be heard) as well as rule on the fairness of any propose class settlement prior to approving the settlement and issuing any order related to the settlement that might negatively impact any individual plaintiff.

Judge Fallon in Vioxx as well as other “Quasi Class Action MDL judges” prior to the current Xarelto settlement have in fact held fairness hearings per FRCP 23(e) in all MDL mass settlements in which the court has involved itself via settlement related orders or other oversight.

Judge Fallon did not conduct fairness hearings before issuing orders related to the Xarelto settlement.

These “fairness hearings” are intended (according to “Quasi Class Action MDL judges”) to provide extend the protections provided absent parties in Class Action to absent parties in MDLs. In the MDL context “absent parties” would be all plaintiffs not represented by plaintiff’s leadership (retained by the leadership firms)

Why Do Xarelto Plaintiffs deserve Less Judicial protection than Vioxx Plaintiffs?

Only Judge Fallon could explain why he neglected to follow his own past reasoning (the requirement to conduct fairness hearings) and denied absent Xarelto Plaintiffs the same rights and protections as Vioxx plaintiffs.

Although the proposed Xarelto settlement is repeatedly referred to as a “Private Settlement” (extra udicial) reach by the parties, the label is inaccurate. The settlement was reached after negotiations between defense counsel and plaintiffs’ leadership. Plaintiffs leadership is not a party, nor do they represent any party (plaintiff) other than those retained by their respective firms.

Furthermore, the proposed Xarelto “Private Settlement” ceased to be Private (extrajudicial) the minute the “parties” crossed the threshold of the court seeking an order related to the settlement.

If the courts excuse for not conducting fairness hearings is “because this is a private settlement”, that dog simply won’t hunt.

Any contention that the court is acting under authority agreed to by the parties also fails. Plaintiff Leadership nor Defense Counsel all the “parties”. Plaintiff lead counsel can enter agreements binding on the clients retained by their firms (those parties) however, leadership does not represent all “parties” and therefore cannot stipulate to jurisdiction on behalf clients they do not represent. Additionally, issues related to subjected matter jurisdiction  cannot be waived by stipulation or agreement by the parties.

Jurisdiction Under the “All Writs Act”?

[A]ll courts established by Act of Congress may issue all writs necessary or appropriate in aid of their respective jurisdictions and agreeable to the usages and principles of law.”  28 U.S.C. § 1651(a).

In should be noted that Judge Weinstein, Judge Fallon  and “Quasi Class Action MDL Judges” never appear to claim to have  actual jurisdiction over MDL settlements, they instead cite their inherent authority, which would arise under the “All Writs Act”:

“All courts established by Act of Congress may issue all writs necessary or appropriate in aid of their respective jurisdictions and agreeable to the usages and principles of law.”  28 U.S.C. § 1651(a).”

The All Writs Act however, only provides “inherent authority” over subject matter for which the given Federal Court otherwise has jurisdiction. Absent Jurisdiction over the Subject Matter of MDL settlement, MDL Judges have no inherent authority  arising under 28 U.S.C. § 1651 related to the same subject matter (MDL settlements).

 

Judicial Activism Morphing into Tyranny

Judge Fallon, as well as other MDL judges who subscribe to the quasi-class action theory within the restraints of FRCP 23(e), have in the past been potentially guilty of well-intended judicial activism even when judicial acts arising from that activism may have strayed beyond their  jurisdiction.

The inherent problem always accompanying judicial activism is the risk of activism turning into tyranny.

Xarelto Plaintiffs aggrieved by the proposed settlement, with no forum in which to voice their grievances, while plaintiff leadership arguably acting to their common detriment and a court turning a deaf ear to their plight, might justifiably feel they are victims of judicial tyranny.

Many Judicial Scholars have expressed concern over the possible negative consequences of judicial activism. Many of the concerns expressed by these judicial scholars have now been realized in the proposed Xarelto Settlement.

The Author would argue that Judge Fallon’s failure to conduct fairness hearings, while issuing orders related to the Xarelto settlement, that may negatively impact individual plaintiffs, crossed the line from judicial activism to  judicial tyranny.

 

Don’t Take My Word for It

Due to the fact several members of Xarelto leadership directly threatening me and attempting to lead attorneys representing absent Xarelto plaintiffs (non-leadership) firms, to believe they are somehow at risk of ethical violations if they take the opinions of a non-lawyer (me) into consideration, I will provide the several links below to scholarly papers and articles written by judicial scholars who are actually attorneys. Draw your own conclusions.

Mass Tort Deals: Backroom Bargaining in Multidistrict Litigation

Elizabeth Chamblee Burch

https://www.amazon.com/Elizabeth-Chamblee-Burch/e/B00G61EI2I/ref=dp_byline_cont_ebooks_1

About Professor Burch: http://www.law.uga.edu/profile/elizabeth-chamblee-burch

Mass Tort Deals: Backroom Bargaining in Multidistrict Litigation is available for purchase on Amazon. Professor Burch has been conducing research related to MDL settlements for many years. Her most recent work “Mass Tort Deals: Backroom Bargaining in Multidistrict Litigation” is an eye opening read even for those that believe they are already familiar with all of the “dirty little lies and secrets” of mass torts.

Other work by Professor Burch includes “Monopolies in Mass Torts”

https://digitalcommons.law.uga.edu/cgi/viewcontent.cgi?referer=https://www.google.com/&httpsredir=1&article=2113&context=fac_artchop

 

You can obtain a copy of Monopolies in Mass Torts free at the link above. This paper is somewhat of a prequel to Mass Tort Deals: Backroom Bargaining in Multidistrict Litigation. If you read the prequel you will want to buy the book.

 

DUBIOUS DOCTRINES: THE QUASI-CLASS ACTION  by Linda Mullenix

https://scholarship.law.uc.edu/cgi/viewcontent.cgi?article=1095&context=uclr

Note: This article written by Linda Mullenix in 2012 is as apt today as the day it was written.

About Professor Mullenix:  https://law.utexas.edu/faculty/linda-s-mullenix

Excepts:

In the past few years, the term ―quasi-class action has been appearing with increasing, uncritical frequency in a spate of federal court decisions. While it may be premature to characterize these sporadic references as a trend, it is perhaps soon enough to call attention to the misuse of loose labels that carry with them significant consequences. Before the quasi-class action gains any further traction, there are several valid reasons for definitively quashing this quasi

Before the inspired fabrication of the quasi-class action, global agreements accomplished under MDL auspices had to be settled pursuant to formal class requirements and due process protections. By engrafting the label quasi-class action onto MDL procedure, self-interested actors have created a perfect staging ground for negotiating back-room deals that carry a false aura of judicial legitimacy, liberated from the constraints of the formal class action rule.

MDL judges, in turn, by endorsing the concept of the quasi-class action have greatly expanded the scope of their authority and have become complicit in allowing private parties to accomplish the very backdoor settlements that the Supreme Court and federal courts have disallowed for decades. The quasi-class action, then, represents an ultimate, cynical expression of an aggregate claims-resolution model that enables self-interested actors to resolve claims in the actors‘ best interests rather than the interests of injured claimants.

At first blush, the sheer frequency of federal use of the term quasi-class action would seem to suggest that the quasi-class action is a well-recognized and well-established doctrine in federal jurisprudence. Since 1946, sixty-eight federal cases have cited the label. However, careful reading of this case law suggests an entirely different conclusion: the quasi-class action is a phantasm. None of these cases actually discussed the concept of the quasi-class action, and rarely-cited authority is inapposite or inaccurate.

Important Case Law

Although SCOTUS has yet to address the question : Does and MDL Judge (like a Class Action Judge) have jurisdiction over settlement, as the question has yet to be presented to SCOTUS, the high court has ruled on other questions in a manner which may be of value to any firm representing a plaintiff in the Xarelto litigation if said plaintiff case is dismissed or otherwise prejudiced by any of the orders related to or arising from the prosed Xarelto Settlement.

Lexecon v Milberg (Scotus)

https://www.oyez.org/cases/1997/96-1482

Note: Lexecon did not directly address the question of an MDL Judges jurisdiction over MDL settlement however, SCOTUS made it clear that USC 1407 does not extend an MDL judges jurisdiction beyond the exact language codified by Congress in 1407.

Federal Judges have broad discretion over many matters however, Federal Judges have no discretion in any matter (subject matter nor personal) beyond the specific grant of jurisdiction by Congress under which the court acts.

Question

May a federal district court conducting “pretrial proceedings” under 28 USC section 1407(a) invoke section 1404(a) to assign a transferred case to itself for trial?

No. In an opinion delivered by Justice David H. Souter, the Court held that a district court conducting pretrial proceedings pursuant to section 1407(a) has no authority to invoke section 1404(a) to assign a transferred case to itself for trial. The Court noted that the Panel’s section 1407(a) instructions are crouched in the word “shall,” which “creates an obligation impervious to judicial discretion.” Justice Souter wrote for the Court that, “the straightforward language imposing the Panel’s responsibility to remand… bars recognizing any self-assignment power in a transferee court.” The opinion was unanimous except insofar as Justice Antonin Scalia did not join Part II-C.

Lexecon Inc. was a defendant in a class action lawsuit. Under 28 USC section 1407(a), the lawsuit was transferred for pretrial proceedings to the District of Arizona. Section 1407(a) authorizes the Judicial Panel on Multidistrict Litigation to transfer civil actions with common issues of fact “to any district for coordinated or consolidated pretrial proceedings,” but provides that the Panel “shall” remand any such action to the original district “at or before the conclusion of such pretrial proceedings.” After claims against it were dismissed, Lexecon brought suit against Milberg Weiss Bershad Hynes & Lerach and others (Milberg) in the class action lawsuit in the Northern District of Illinois. Ultimately, the Panel, under section 1407(a), ordered the case transferred to the District of Arizona. Afterwards, Lexecon moved for the Arizona District Court to remand the case to Illinois. Milberg filed a countermotion requesting the Arizona District Court to invoke section 1404(a) to “transfer” the case to itself for trial. Ultimately, the court assigned the case to itself and the Court of Appeals affirmed its judgment.

 

AMCHEM PRODUCTS, INC., et al., PETITIONERS v. GEORGE WINDSOR et al.

Note: AMCHEM arose from the asbestos litigation, the ruling addressed attempts to settle cases filed in MDLs as well as cases filed in Class Actions. SCOTUS did not address the question of MDL Courts jurisdiction (nor lack thereof) over MDL settlement as this issue was not raised. SCOTUS ruling in AMCHEM did however make it clear that any mass tort judge, whether presiding over an MDL or a Class Action, has a duty to protect the interest of “absent plaintiffs”.

Excepts from AMCHEM

This case concerns the legitimacy under Rule 23 of the Federal Rules of Civil Procedure of a class action certification sought to achieve global settlement of current and future asbestos related claims. The class proposed for certification potentially encompasses hundreds of thousands, perhaps millions, of individuals tie d together by this commonality: each was, or some day may be, adversely affected by past exposure to asbestos products manufactured by one or more of 20 companies. Those companies, defendants in the lower courts, are petitioners here.

Rule 23(e), on settlement of class actions, reads in its entirety: “A class action shall not be dismissed or compromised without the approval of the court, and notice of the proposed dismissal or compromise shall be given to all members of the class in such manner as the court directs.” This prescription was designed to function as an additional requirement, not a superseding direction, for the “class action” to which Rule 23(e) refers is one qualified for certification under Rule 23(a) and (b). Cf. Eisen, 417 U. S., at 176-177 (adequate representation does not eliminate additional requirement to provide notice). Subdivisions (a) and (b) focus court attention on whether a proposed class has sufficient unity so that absent members can fairly be bound by decisions of class representatives. That dominant concern persists when settlement, rather than trial, is proposed.

The settling parties, in sum, achieved a global compromise with no structural assurance of fair and adequate representation for the diverse groups and individuals affected. Although the named parties alleged a range of complaints, each served generally as representative for the whole, not for a separate constituency. In another asbestos class action, the Second Circuit spoke precisely to this point:

[W]here differences among members of a class are such that subclasses must be established, we know of no authority that permits a court to approve a settlement without creating subclasses on the basis of consents by members of a unitary class, some of whom happen to be members of the distinct subgroups. The class representatives may well have thought that the Settlement serves the aggregate interests of the entire class. But the adversity among subgroups requires that the members of each subgroup cannot be bound to a settlement except by consents given by those who understand that their role is to represent solely the members of their respective subgroups.” In re Joint Eastern and Southern Dist. Asbestos Litigation, 982 F. 2d 721, 742-743 (CA2 1992), modified on reh’g sub nom. Inre Findley, 993 F. 2d 7 (CA2 1993).

The Third Circuit found no assurance here–either in the terms of the settlement or in the structure of the negotiations–that the named plaintiffs operated under a proper understanding of their representational responsibilities. See 83 F. 3d, at 630-631. That assessment, we conclude, is on the mark.

The argument is sensibly made that a nationwide administrative claims processing regime would provide the most secure, fair, and efficient means of compensating victims of asbestos exposure. Congress, however, has not adopted such a solution. And Rule 23, which must be interpreted with fidelity to the Rules Enabling Act and applied with the interests of absent class members in close view, cannot carry the large load CCR, class counsel, and the District Court heaped upon it. 

Subject Matter Jurisdiction Case Law 

Note: There are literally thousands of appellate rulings related to Lower Courts (Federal) issuing judgments and orders in excess of their jurisdiction. The citations below are merely examples of the vast number of rulings on the subject.

Void judgment is one entered by court that lacks the inherent power to make or enter the particular order involved, and it may be attacked at any time, either directly or collaterally; such a judgment would be a nullity, People v. Rolland 581 N.E.2d 907, Ill.App. 4 Dist. 1991)..

Invalidity need to appear on face of judgment alone that judgment or order may be said to be intrinsically void or void on its face, if lack of jurisdiction appears from the record, Crockett Oil Co. v. Effie, 374 S.W.2d 154 (Mo.App. 1964).

Note: MDL Court Judges imposing themselves into MDL settlements never seem to actually claim to have jurisdiction in the record, instead they  claim to have “inherent authority”. No authority exists absent jurisdiction.

Decision is void on the face of the judgment roll when from four comers of that roll, it may be determined that at least one of three elements of jurisdiction was absent: (1) jurisdiction over parties, (2) jurisdiction over subject matter, or (3) jurisdictional power to pronounce particular judgment that was rendered, B & C Investments, Inc. v. F & M Nat. Bank & Trust, 903 P.2d 339 (Okla. App. Div. 3, 1995).

A void judgment which includes judgment entered by a court which lacks jurisdiction over the parties or the subject matter, or lacks inherent Power to enter the particular judgment. or an order procured by fraud,can be attacked at any time, in any court, either directly or collaterally, provided that the party is properly before the court. Long v. Shorebank Development Corp., 182 F.3d 548 ( C.A. 7 Ill. 1999).

A void judgment is one which from its inception was a complete nullity and without legal effect, Lubben v. Selective Service System Local Bd. No. 2 7, 453 F.2d 645, 14 A.L.R. Fed. 298 (C.A. 1 Mass. 1972).

A void judgement is one which from its inception and forever continues to be absolutely null. without legal efficacy, ineffectual to bind the parties or to support a right, of no legal force and effect whatever, and incapable of enforcement in any manner or to any degree – Loyd v. Director, Dept. of Public Safety, 480 So. 2d 577 (Ala. Civ. App. 1985).

A judgment shown by evidence to be invalid for want of jurisdiction is a void judgment or at all events has all attributes of a void judgment, City of Los Angeles v. Morgan, 234 P.2d 319 (CaLApp. 2 Dist. 1491).

Res judicata consequences will not be applied to a void judgment which is one which from its inception is a complete nullity and without legal effect, Allcock v. Allcock 437 N.E. 2d 392 (Ill. App. 3 Dist. 1982).

Void judgment is one which has no legal force or effect whatever, it is an absolute nullity, its invalidity may be asserted by any person whose rights are affected at any time and at any place and it need not be attacked directly but may be attacked collaterally whenever and wherever it is interposed, City of Lufkin v. McVicker, 510 S.W. 2d 141 (Tex. Civ. App. – Beaumont 1973 1991)..

Disclaimer: The author of this article, John Ray, is not a lawyer. Nothing in this article should be taken as legal advice. The opinions expressed in this article are the opinions of the author. Publication of this article by any third party should not be considered an endorsement of nor agreement with the opinions expressed by the author.

 

 

 

Read More

False Narratives Opioids and Xarelto

Mass Tort Nexus is compiling an evidentiary package for law firms who intend to reject the current Xarelto settlement offer and prepare for trial. This article represents an extremely small segment of what any firm who prepares for trial will have at their disposal; however, we believe most everyone involved in Mass Torts might find the following topic interesting.

It is well known how Big Pharma allegedly promoted a false narrative regarding Opioids and the risk posed by these highly addictive drugs. Despite the fact that thousands of people were dying every year from opioid overdose, doctors seemed unaware that the narrative they had bought into was false.

What might the death toll ultimately be for the new anticoagulants?

We are aware that both the Xarelto primary defendants are also accused of being party to the opioid false narrative conspiracy in opioid litigation complaints.  If Big Pharma can keep doctors prescribing opioids like skittles for decades, despite the rising death toll, how hard could it be to keep doctors prescribing an anticoagulant with a few tweaks to the truth?

Why Did Doctors Prescribe Xarelto and Why do they Continue to Prescribe Xarelto?

The clinical trials for Xarelto did not prove the drug to be superior in efficacy to Warfarin, only “non inferior.” It was not a better drug from an efficacy stand point. Doctors had no reason to switch patients to Xarelto because it “worked better” than Warfarin.

Xarelto is exponentially more expensive that Warfarin, so doctors had to reason to switch patients to Xarelto based on cost.

What were the makers of Xarelto able to claim about their new (unproven in the general patient population) to convince them to switch patients to Xarelto?

  1. No Routine Blood Testing (monitoring.)
  2. No Dietary Restrictions.

What if these claims were false, patients do need routine blood monitoring while on Xarelto?

What if patients taking Xarelto do need to restrict their diet (not consume certain food products?)

Would doctors keep prescribing Xarelto? Probably not, if the arguably false narrative first presented to them was corrected (warned) as having been false. That said, once a claim is made, people, including doctors, are not likely to realize that the claim is no longer being made once they have bought into the claim, unless they are specifically informed that the claim might have been false.

The following will explain why the makers of Xarelto may have stopped claiming (in their television and print ads,) that patients taking Xarelto did not need routine blood testing nor adhere to any dietary restrictions.

We will first review Xarelto television spots beginning in 2013 and more recent ads. Then we will explain why the makers of Xarelto quit claiming that users of their product stopped claiming that:

  1. No Routine Blood Testing (monitoring) was needed.
  2. No dietary restrictions.

You may view a larger selection of ads than those provided below at: https://www.ispot.tv/brands/ISA/xarelto

2013: Xarelto Bob Ad  (both “no routine monitoring” and “no dietary restrictions claims made”.)

 

 

 

 

 

 

 

https://www.ispot.tv/ad/7dJt/xarelto-bob

Start at 16 Seconds, “Bob took Wafarin and made a monthly trip to the clintic to get his blood tested but not anymore.”

Start at  36 Seconds,   “Xarelto is the first and only once per day prescription blood thinner… That does not require rountine Blood Monitoring.”

Start at 57 Seconds, “and there’s no dietary restrictions…Bob can eat the health foods he likes. ”

2014 Mary Ad (both “no routine monitoring” and “no dietary restrictions claims made.”)

 

 

 

 

 

 

https://www.ispot.tv/ad/7pGC/xarelto-mary-song-by-arturo-cardelus

Start at 12 Seconds  “Which required monthly testing, but that’s history.”

Start at 56 Seconds “Plus with no Known Dietary Restrictions.”

2015  Arnold Palmer (they did not specifically say no routine testing and dietary restrictions, but they  implied the claims. )

 

 

 

 

 

 

https://www.ispot.tv/ad/AYGi/xarelto-game-plan-feat-chris-bosh-arnold-palmer-brian-vickers

Start at 29 Seconds (claims worked into general conversation)

article link: https://www.masstortnexus.com/News/366/Did-Xarelto-the-Drug-Arnold-Palmer-Promoted-Lead-to-His-Death?

2016: Jerry West (neither of the claims were made in this ad.)

 

 

 

 

 

 

https://www.ispot.tv/ad/ARh_/xarelto-high-risk-of-stroke-featuring-jerry-west

2017  Xarelto “Protect Themselves” ad feature authority figures  (neither of the claims were made in this ad.)

 

 

 

 

 

 

 

 

https://www.ispot.tv/ad/wtdp/xarelto-protect-themselves

2018  “Learn all you can ad” (we do not think irony was intended), (neither of the claims were made in this ad)

 

 

 

 

 

 

https://www.ispot.tv/ad/wPmP/xarelto-learn-all-you-can

So Why Did the Makers of Xarelto Quit Making Their “Claims to Fame?”

We will first address why the makers of Xarelto most likely stopped making the “no rountine blood testing (monitoring claim.) This answer to this one is easy; Because the FDA warned them about making this claim.

It is difficult to understand why the makers of Xarelto did not unilaterally determine (and warn that their original messaging no routine blood monitoring needed) might have been misleading based solely on the number of adverse events reported to the FDA since the product’s introduction.

______________________________________________________________________________________________________

 

 

Food and Drug Administration

Silver Spring, MD 20993

Roxanne McGregor-Beck, Director

Johnson & Johnson International, Inc.

1000 Route 202 South

P.O. Box 300

Raritan, New Jersey 08869-0602

 

RE: NDA #202439

XARELTO (rivaroxaban) tablets

MA #215

Dear Ms. McGregor-Beck:

The Office of Prescription Drug Promotion (OPDP) of the U.S. Food and Drug Administration (FDA) has reviewed a direct-to-consumer (DTC) print advertisement (K02XS121040 AF) (Print Ad) for XARELTO (rivaroxaban) tablets (Xarelto) submitted by Johnson & Johnson International, Inc. (Johnson & Johnson) on behalf of Janssen Pharmaceuticals, Inc. under cover of Form FDA 2253 and observed during routine surveillance in the January/February 2013 issue of WebMD magazine. The Print Ad is false or misleading because it minimizes the risks associated with Xarelto and makes a misleading claim. Thus, the Print Ad misbrands Xarelto in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 352(n) and FDA implementing regulations. 21 CFR 202.1(e)(5)(i); (e)(7)(viii), (ix).

Background:

Below is the indication and summary of the most serious and most common risks associated with the use of Xarelto.1 According to its FDA-approved product labeling (PI), in pertinent part:

Xarelto is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

There are limited data on the relative effectiveness of XARELTO and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well controlled.

 The PI for Xarelto contains Boxed Warnings regarding increased risk of stroke after discontinuation in patients with nonvalvular atrial fibrillation and the risk of spinal/epidural

hematoma. The PI also contains Contraindications regarding active pathological bleeding and severe hypersensitivity reaction to Xarelto, as well as Warnings and Precautions regarding the risk of bleeding, use in patients with renal impairment and hepatic impairment, use with P-gp and strong CYP3A4 inhibitors or inducers, and risk of pregnancy related hemorrhage. The most common adverse reactions with Xarelto were bleeding complications.

Minimization of Risk Information

 Promotional materials are false or misleading if they fail to present risks associated with a drug with a prominence and readability reasonably comparable with the presentation of information relating to the benefits of the drug. Factors impacting prominence and readability include typography, layout, contrast, headlines, paragraphing, white space, and other techniques apt to achieve emphasis. The Print ad prominently presents various efficacy claims for Xarelto, such as, but not limited to, the following, that are presented in large, bolded and/or colorful text and graphics (emphasis original):

• “If you have atrial fibrillation (AFib)”

• “Ready to break your AFib routine?”

• “XARELTO® is the first and only once-a-day prescription blood thinner for patients with AFib not caused by a heart valve problem, that is proven to reduce

the risk of stroke—without routine blood monitoring.”

• “…With XARELTO®, there’s no routine blood monitoring—so you have more time for yourself. There are no dietary restrictions, so you’re free to enjoy the healthy foods you love. And there are no dosage adjustments, which means you can manage your risk with just one pill a day, taken with your evening meal. Learn how XARELTO® can help simplify your AFib-related stroke risk treatment….”

In contrast, the risk information is presented on the preceding adjacent page without any of the emphasis (i.e. color scheme, borders, layout, and graphics) used with the efficacy claims. The result is a presentation which appears unconnected to the efficacy claims and is therefore not likely to draw readers’ attention. This overall presentation misleadingly  minimizes the risks associated with Xarelto because it fails to convey this important risk information with a prominence and readability reasonably comparable to the efficacy claims. We note that the Print Ad contains the statement, “Please see accompanying Medication Guide on the following pages” (emphasis original) at the bottom of the page, and that risk information is presented on an adjacent page, but this is not sufficient to mitigate the overall misleading presentation.

Misleading Claim

 The Print Ad includes the following claim (emphasis original):

• “And there are no dosage adjustments…”

The above claim misleadingly suggests that dosage adjustments are not necessary with Xarelto. However, according to the DOSAGE AND ADMINISTRATION section of the PI, the dose should be lowered to 15 mg once daily for patients with renal impairment who may have a CrCL of 15 to 50 mL/min. In addition, the WARNINGS AND PRECAUTIONS section of the PI states, “…Periodically assess renal function as clinically indicated…and adjust therapy accordingly….” Thus, patients with renal impairment may need to have their dosage adjusted while on Xarelto therapy.

Conclusion and Requested Action

For the reasons discussed above, the Print Ad misbrands Xarelto in violation of the FD&C Act, 21 U.S.C. 352(n) and FDA implementing regulations. 21 CFR 202.1(e)(5)(i); (e)(7)(viii), (ix). OPDP requests that Johnson & Johnson immediately cease the dissemination of violative promotional materials for Xarelto such as those described above. Please submit a written response to this letter on or before June 20, 2013, stating whether you intend to comply with this request, listing all promotional materials (with the 2253 submission date) for Xarelto that contain violations such as those described above, and explaining your plan for discontinuing use of such violative materials.

Please direct your response to the undersigned at the Food and Drug Administration,

Center for Drug Evaluation and Research, Office of Prescription Drug Promotion, 5901-B Ammendale Road, Beltsville, Maryland 20705-1266 or by facsimile at (301) 847-8444. To ensure timely delivery of your submissions, please use the full address above and include a prominent directional notation (e.g. a sticker) to indicate that the submission is intended for OPDP. Please refer to MA# 215 in addition to the NDA number in all future correspondence relating to this particular matter. OPDP reminds you that only written communications are considered official. The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for Xarelto comply with each applicable requirement of the FD&C Act and FDA implementing regulations.

Sincerely,

{See appended electronic signature page}

Zarna Patel, Pharm.D.

Regulatory Review Officer

Office of Prescription Drug Promotion

{See appended electronic signature page}

Amy Toscano, Pharm.D., RAC, CPA

Team Leader

Office of Prescription Drug Promotion

____________________________________________________________________________________

It is difficult to understand why the makers of Xarelto did not unilaterally determine (and warn that their original messaging (no routine blood monitoring needed) might have been misleading bases solely on the number of adverse events reported to the FDA since the products introduction.

 

 

 

 

 

https://fis.fda.gov/sense/app/d10be6bb-494e-4cd2-82e4-0135608ddc13/sheet/59a37af8-d2bb-4dee-90bf-6620b1d5542f/state/analysis

 

 

 

 

 

 

https://fis.fda.gov/sense/app/d10be6bb-494e-4cd2-82e4-0135608ddc13/sheet/59a37af8-d2bb-4dee-90bf-6620b1d5542f/state/analysis

Having not corrected their prior claims (warned) related to the need for routine blood testing (monitoring) the makers of Xarelto did add the words underlined (below) to the label for Xarelto NDA -022406 in November of 2018. This statement in no way corrects the arguably false prior statements related to “No Routine Blood Testing” needed.  This statement simply warns that many of the common “blood monitoring tests used” are not recommended for individuals using Xarelto. A more accurate statement might have been: “These tests have no diagnostic value for individuals on Xarelto,” as the drug skews the test, and not in a predictable fashion, which would allow for adjustment of the test results.

Do these two statements seem the same to you?

  1. No Routine Blood Monitoring Needed with Xarelto.
  2. The test routinely used for anticoagulation monitoring has no diagnostic value for individuals taking Xarelto.

Which of the above two statements would likely increase revenues from the drug and which one would likely have the opposite effect?

11/07/2018 (SUPPL-29)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Risk of Bleeding

Reversal of Anticoagulant Effect

Additions and/or revisions underlined:

… anticoagulant activity of rivaroxaban. Use of procoagulant reversal agents, such as prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa, may be considered but has not been evaluated in clinical efficacy and safety studies. Monitoring for the anticoagulation effect of rivaroxaban using a clotting test (PT, INR or aPTT) or anti-factor Xa (FXa) activity is not recommended.

https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=287

“Now We Turn to “No Dietary Restrictions Necessary”

 06/28/2017 (SUPPL-23)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Risk of Bleeding

(additions underlined)

(excerpts)

5.6 Use with P-gp and Strong CYP3A4 Inhibitors or Inducers

(additions underlined)

Avoid concomitant use of XARELTO with known combined P-gp and strong CYP3A4 inhibitors.

Avoid concomitant use of XARELTO with drugs that are known combined P-gp and strong CYP3A4 inducers.

7 Drug Interactions

7.1 General Inhibition and Induction Properties

(additions underlined)

Rivaroxaban is a substrate of CYP3A4/5, CYP2J2, and the P-gp and ATP-binding cassette G2 (ABCG2) transporters. Combined P-gp and strong CYP3A4 inhibitors increase exposure to rivaroxaban and may increase the risk of bleeding. Combined P-gp and strong CYP3A4 inducers decrease exposure to rivaroxaban and may increase the risk of thromboembolic events.

7.2 Drugs that Inhibit Cytochrome P450 3A4 Enzymes and Drug Transport Systems

Interaction with Combined P-gp and Moderate CYP3A4 Inhibitors in Patients with Renal Impairment

XARELTO should not be used in patients with CrCl 15 to <80 mL/min who are receiving concomitant combined P-gp and moderate CYP3A4 inhibitors (e.g., erythromycin) unless the potential benefit justifies the potential risk.

End excerpt

What is the significance of the above?

The inducers make the user more susceptible to clots (ischemic stroke, DVT, PE, etc.)

The inhibitors make the user more likely to bleed.

On a side note, the GI tract is significant to the actions of CYPE4A as well as P-gp. And if you remember from above, what was the most reported AE with Xarelto:

 

So what does the use of Strong and Moderate CYP34A and P-gp Inhibitors and Inducers have to do with dietary restrictions?

Most everyone is familiar with the fact that some drugs carry a warning about restricting grapefruit juice from your diet while on the given drug (i.e. statins).

The relation to the above and the “no dietary restrictions” claim, that the makers of Xarelto use to promote their drug (and then stopped making but did not correct the narrative) is simple. There are numerous foods which are CYP34A, and P-gp inhibitors and/or inducers. We provide a small sampling of foods and dietary supplements below.

The dietary restrictions associated with Warfarin restricted foods high in Vitamin K, like Kale (yummy Kale).

Xarelto Potential Food Restrictions

It is worth nothing that due to genetic differences, the strength of a given CYP34A and P-gp Inhibitor or Inducer necessary to interfere with a drug is not the same for everyone. Women as a general rule are more susceptible to the effects of CYP34A and P-gp Inhibitors or Inducers than men.

Grape Fruit Juice: Inhibits CYP34A and P-gp Seville Orange Juice CYP34A and P-gp
Lime Juice Inhibits CYP34A Lemon Juice Inhibits CYP34A
Pomegranate Juice Inhibits CYP34A Star Fruit Juice Inhibits CYP34A
Kiwi Juice Inhibits CYP34A Passion Fruit Juice Inhibits CYP34A
 St. John’s wort Induction of P-gp Ginkgo Biloba Induces P-gp

 In addition to food interactions Approximately 50% of prescription drugs either induce or inhibit CYP34A or P-gp.

While many drugs are deactivated by CYP3A4, there are also some drugs which are activated by the enzyme. Some substances, such as grapefruit juice and some drugs, interfere with the action of CYP3A4. These substances will therefore either amplify or weaken the action of those drugs that are modified by CYP3A4.

https://en.wikipedia.org/wiki/CYP3A4

So, what the Xarelto label (warnings) universally adequate in 2015, 2016 or today?

We think not!

Read More

Mass Tort Nexus: Xarelto Settlement Update

Xarelto Settlement: Power in Numbers

(April 23, 2019) As stated in previous Mass Tort Nexus articles, we are of the opinion that the current proposed Xarelto Settlement is “dead on arrival.” Based on our conversations with non-leadership firms, we are of the belief that there is an implacable intention to reject or recommend that their clients reject the current settlement offer.

Numerous additional firms have contacted Mass Tort Nexus since our first article was published related to the proposed settlement last week. Since that release, Mass Tort Nexus has received ongoing inquiries from firms asking the same basic question:

Do the leadership firms control enough of the client cases in the Xarelto litigation, to reach a settlement participation level acceptable to the defendant under the current proposal, without regard to the number of non-leadership firms that might reject the offer?

In order to provide an informed answer to this question Mass Tort Nexus conducted an analysis:

Mass Tort Nexus accessed the JMPL and the USDC ED Louisiana ECF links to determine how many cases are pending in MDL 2592. For this analysis we are not considering cases filed in other venues; however, there is no cause to believe that cases in other venues would be of sufficient volume to skew these findings.

According to the JPML, there are 23,866 cases pending in Xarelto MDL 2592 as of 04/15/2019. We believe no major change in these numbers has occurred in the three days that have elapsed between the latest JPML report and this analysis.

We will assume for arguments sake, that all the PSC members are going to accept the proposed Xarelto settlement. From a pure business perspective, the PSC members will be paid according to the work their firms have performed for the “common benefit”, which for many PSC firms may be a more significant sum than the fees they would earn from the clients they represent. Based on this reasoning, we will assume that all of the PSC member firms will accept the current settlement offer.

Mass Tort Nexus accessed Pacer to determine how many cases were on file for the Plaintiff Steering Committee (PSC) members.

The following are the result of that review:

PSC Member Firm MDL Cases
Ferrer Poirot 1,679
Beasley Allen 1,466
Morgan & Morgan 800
Levin Papantonio 650
Aylstock Witkin Kreis Overholtz 515
Schlicter, Bogard & Denton 118
Seeger Weiss 100
Nast Law 90
Ross Feller Casey 70
Levine Fishbein & Berman 50
Weitz & Luxenberg P.C. 81
Goza & Honnold, L.L.C. 310
Total Client MDL Cases PSC Members 5,929 24.82%
Total Client Cases MDL Non-PSC Members 17,937 75.18%
Xarelto MDL 2592 23866
http://www.laed.uscourts.gov/case-information/mdl-mass-class-action/xarelto/contacts/plaintiffs-steering-committee
https://www.jpml.uscourts.gov/sites/jpml/files/Pending_MDL_Dockets_By_Actions_Pending-April-15-2019.pdf

Based on the results of our findings, of cases filed by PSC members, “Leadership” represents 5,929 (24.82%) of the 23,866 Xarelto MDL 2592 cases on file, while non leadership firms represent 17,937 (75.18%) of the cases on file.

Therefore, the answer to the question “does leadership directly control enough of total number of Xarelto cases to meet the participation requirements by the defendant is NO, based on this informed analysis.

Based on information received from reliable sources, the “Participation Level” defendants require to “go through” with the current offer is 90%. Of course, the defendants would have the option of going through with the settlement at a participation level of less than 90% however, it would not make sense for a defendant in any mass litigation to move forward with a settlement, that left several thousand cases moving towards trial. The number of cases left unsettled is more important than the representation of that number as a percentage.

Note: Mass Tort Nexus’ analysis of the number of cases under the direct control of leadership did not include any cases filed by other firms, which may have subsequently been referred to leadership firms. Therefore, leadership may have direct control over a larger number of cases that cannot be confirmed through our analytical methodology. Without regard to the foregoing, Mass Tort Nexus was able to verify the number of cases on file by firms who have expressed an implacable intent to reject the current offer, and therefore, the conclusions reached through our analysis would not  impact the unknown variable arising from cases filed by non-leadership firms, that have been subsequently referred to leadership firms.

To complete our analysis, we calculated the number of cases that could reject the settlement offer and overall participation still reach a given percentage participation level.

 

Participation Level (PL) Maximum Rejections to Achieve PL
95% 1,193.3
90% 2,386.6
85% 3,579.9
80% 4,773.2
75% 5,966.5
70% 7,159.8
65% 8,353.1
60% 9,546.4
55% 10,739.7
50% 11933

 

Based on conversations with numerous firms with “small” to “large” dockets, in the Xarelto MDL (also verified in the same manner as MTN verified leaderships client numbers), Mass Tort Nexus is of the following opinion:

Firms that have expressed their position to be in absolute rejection of the current offer, (nothing can convince them to change their minds), that the hold outs from these firms along will prevent the participation level in the settlement from reaching 80%.

Firms that are leaning toward rejection but could possibly change their minds (if they split down the middle on their final decision, half going one way and half going the other) would likely prevent the settlement acceptance level form reaching 70%.

If additional firms that have not communicated with Mass Tort Nexus also add to the “implacable rejectors” count, reaching a participation percentage acceptable to defendants becomes even less probable.

Mass Tort Nexus would like to clarify past comments, as well as comments made in this article, and those that may be forthcoming in future coverage of the proposed Xarelto settlement. Our coverage of this issue is not intended to be a disparagement of the firms in leadership in the Xarelto MDL. Leadership did not make the current settlement offer, the defendants made the offer. When a defendant approaches leadership wishing to discuss settlement, leadership engages in the discussion. When defendants make an offer, leadership presents that offer to the non-leadership firms involved in the litigation (becoming the messenger.)  If the offer does not result in a consummated settlement, leadership will have to “go back to the table” with the defendants. Leadership can not be seen to have been the cause of the previous settlement offer “falling through” and retain the credibility with the defendants needed for additional rounds of negotiations.  It is never our intent to “shoot the messenger” even when our opinions differ from the message.

https://www.jpml.uscourts.gov/sites/jpml/files/Pending_MDL_Dockets_By_Actions_Pending-April-15-2019.pdf

 

Read More

Analysis of Proposed Xarelto Settlement Discount Rates – Debunking Defendants Rationale

 

 

Analysis of Proposed Xarelto Settlement Discount Rates

Debunking Defendants Rationale

 This is a follow up to the Mass Tort Nexus article “Xarelto Settlement: Dead on Arrival” – link: Xarelto-Settlement-Dead-on-Arrival? April 15, 2019

 

(MASS TORT NEXUS MEDIA) This article is intended to address the Xarelto defendants’ contentions that certain settlement offer “discounts” are justified for client cases arising in 2015 and 2016 due to changes in the FDA label,  which the defendant contends brought warnings contained in the label into adequacy. This paper will also address defendant’s contention that cases arising under the laws of the States of Texas and Michigan merit a massive discount in settlement value (offers).

We will focus on the Xarelto label change from 11/07/2018, AND an additional label change was made on 01/15/2019 related to Eosinophilia, which could be relevant to many of the Xarelto cases already filed as well as give rise to a Xarelto Litigation II, that could involve more injured individuals than the current Xarelto Litigation. The relevance and significance of the 01/15/2019 “Eosinophilia” label change will be addressed by Mass Tort Nexus in the near future.

Mass Tort Nexus has also received information that there is an ongoing investigation related to Xarelto potentially causing kidney injury, which may or not be related to Eosinophilia. We will continue to provide more information related to this subject in future articles. Given the new Eosinophilia warning and the investigation related to Kidney injury, and the 11/07/2018 label change related to anticoagulation tests (and the possible impact on future Xarelto case trials) Mass Tort Nexus understands why the defendants might be eager to reach a settlement sooner rather than later. Conversely, there is no reason why plaintiffs’ firms should believe the defendants to be in a superior negotiating position, nor be willing to accept subpar settlements for their existing cases.

It is worth nothing that the 11/07/2018 label change (admission) by the defendant that the most commonly used anticoagulation tests are “not recommended” (in reality likely have no diagnostic value) would make it far more difficult for the defendants to prevail in future trials under the Learned Intermediary Doctrine, as doctors would be less likely to testify that, “they would still do everything exactly as they did when originally prescribing Xarelto.” Had the defendant revealed the foregoing before the prior bellwether trials, the outcome of those trials may have been very different.  It is not surprising that the defendants are eager to settled Xarelto cases without having to face another trial post the 11/07/2018 and 01/15/2019 label changes.

Had the defendants revealed the information related to the most common anticoagulation tests used as “not being recommended” prior to the bellwether trials, doctors testifying in support of a defendants “Learned Intermediary Defense” would likely face questions like these:

 Plaintiffs’ Counsel:  So, Dr. Smith, I see that you performed an INR test to make sure that my client was correctly anticoagulated, that their blood was not to thick or too thin, is that right?

Dr. Smith: Yes

Plaintiffs’ Counsel:  Were you aware that as of 11/07/2018 the defendants recommend that this test not be used and in fact, the literature shows that this test provides no diagnostic value when a person is taking Xarelto?

Dr. Smith: It unlikely that Dr. Smith will say he knew the above when he prescribed Xarelto as he would essentially be admitting to medical malpractice.

Plaintiffs’ Counsel:  So, Dr. Smith, would you still today, follow the same protocol when prescribing Xarelto and use an INR test to make sure the dose of Xarelto did not have the patient’s blood to thick (likely to clot) or too thin (likely to bleed).

Dr. Smith: Unlikely that Dr. Smith would say he would still do what the defendant now recommends he not do.

Plaintiffs’ Counsel:  Dr. Smith, just out of curiosity, do you think the words “No Routine Blood Testing Needed” mean the same thing as “The blood test routinely used don’t work”?

The same line of questioning could be used for doctors that treated a Xarelto bleed or clot.

The contention that any label change could render a product adequately warned for all circumstances and facts relevant to every possible client injury scenario is somewhat preposterous; however, we will address and rebut the defendant’s contentions more directly. Although the Xarelto warning label has been changed numerous times since 2016, we only need to review the label change made on 11/07/2018 (see below) to conclude that the label was not adequate in any clients case in which the referenced anticoagulation tests were used in the “dosing” of Xarelto or the treatment of any Xarelto related injury 11/07/2018.

 11/07/2018 Xarelto Label Change

https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022406s029lbl.pdf

 5.0 Warnings and Precautions

 5.2 Risk of Bleeding

Reversal of Anticoagulant Effect

Additions and/or revisions underlined:

… anticoagulant activity of rivaroxaban. Use of procoagulant reversal agents, such as prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa, may be considered but has not been evaluated in clinical efficacy and safety studies. Monitoring for the anticoagulation effect of rivaroxaban using a clotting test (PT, INR or aPTT) or anti-factor Xa (FXa) activity is not recommended.

Mass Tort Nexus Comment: The highlighted language above was added to the Xarelto FDA (U.S) 0n 11/07/2018, indicating that the use of PT, INR, aPTT anti-factor Xa (FXa) is not recommended. A more accurate statement (warning) would be that these tests have no diagnostic value and should not be used when evaluating dosing for individual patients nor treating bleeds and other conditions related to Xarelto, while the patient has Xarelto in their system.

 We will first address the 11/07/2018 label change as it related to the defendants contentions that the Xarelto label “adequately warned”  of the risks associated with label changes made in 2015 and 2016 as well as the justification (or lack thereof) for any discounts to base settlement offers arising therefrom.

Mass Tort Nexus opinion is as follows:

  1. At minimum, no discount is justified in any case arising before 11/07/2018, in which any of the anticoagulation tests now “not recommended” for use, where used by the prescribing physician immediately before and or any time after prescribing Xarelto, for use by the specific client. The doctor nor the patient were adequately warned with regard to these tests providing any diagnostic value that could serve to mitigate the risks associated with the use of Xarelto.  Additionally, for any client that presented at a medical facility (prior to 11/07/2018), with a Xarelto related injury which resulted in the use of the tests in the process of treating that injury, the warning label was not sufficient to mitigate the risks associated with the use of tests which the defendant now recommends not be used.
  2.  Today the warning label remains inadequate and no discount based on a contention that the warning label was brought into adequacy at any point in the past, is warranted. Until the defendants make further changes to the label including, but not limited to, giving the “anticoagulation” test “warning” greater prominence on the label as well as changing the “not recommended” portion of the statement to reflect a more truthful representation, that is less likely to be overlooked or misunderstood by prescribing physicians. An adequate warning would include information as to why the tests are not recommended (they likely have no diagnostic value).
  3.  It would be difficult for the defendants to argue that the fact that the most commonly used anticoagulation tests “are not recommended” for use in dosing Xarelto or treating a Xarelto injury, would not likely have impacted some doctors decision to prescribe the drug had they been previously warned prior to 11/07/2018. In reality, given the lack of prominence of the 11/07/2018 label change and the fact that no additional educational efforts are being made by defendants (that we are aware of), to insure that doctors are now aware that these tests are “not recommended” and in fact, likely have no diagnostic value, it is probable that the 11/07/2018 warning has not significantly decreased the risk posed Xarelto users, related to this new “warning.

 Before addressing Texas 82.007 and Michigan 600.2946, it is important to point out that one of the most Signiant claims made by the makers of Xarelto, in their effort to establish their product as being superior to Warfarin was that “no routine blood testing (anticoagulation tests) was needed” for patients using Xarelto. Patients taking Warfarin and other VKA’s (Vitamin K Antagonists) do require routine monitoring to insure their anticoagulation levels remain in a therapeutic range.

The “No Routine Blood Testing Needed” claim of the makers of Xarelto, made to the FDA and the public appears to have been very misleading. Mass Tort Nexus has yet to determine how the makers of Xarelto concluded that No Routine Blood Testing was needed for patients taking Xarelto. The 101,743 adverse event reports filed with the FDA related to Xarelto since 2011, is one indicator that “Routine Blood Testing” is needed to insure Xarelto user’s safety. If no Routine Blood Testing was needed, then why have Xarelto patients experienced such a high volume of bleeding and clotting events? The FDA warning letter sent to the makers of Xarelto (provided at the end of this document), is highly relevant to this topic.

If Xarelto was so well designed that a doctor could just assume that patients would be maintained with a therapeutic range (not too thin and likely to bleed or too thick and likely to clot), then why has the FDA received Xarelto 101,753 adverse event reports since 2011, many involving bleeding or clotting that might have been prevented with “routine testing’?

 

Texas and Michigan Cases

To the best of our knowledge, the defendant has yet to raise a defense under Texas 82.007 and Michigan 600.2946 in any case, much less prevail in arguments arising under these laws.

Neither Texas 82.007 nor Michigan 600.294 provide an absolute defense for drug manufacturers. Both state’s laws have language which provide a plaintiff with means, by which to overcome the presumption that these laws provide immunity for a given defendant. We will refer to the language in both States laws as the “savings clause” in the remainder of this article. We will also address each law separately with regard to the burden plaintiffs would face, in overcoming a defense raised under either Texas 82.007 or Michigan 600.294.

First, We Will review the “savings clause” for both Texas 82.007 and Michigan 600.2946 available to plaintiffs to overcome the presumption of drug manufacturer immunity arising under the two laws. See the relevant savings clauses and links to the entire statutes below:

Texas   82.007

(2)(b)  The claimant may rebut the presumption in Subsection (a) as to each defendant by establishing that:

(1)  the defendant, before or after pre-market approval or licensing of the product, withheld from or misrepresented to the United States Food and Drug Administration required information that was material and relevant to the performance of the product and was causally related to the claimant’s injury;

(3)(A) the defendant recommended, promoted, or advertised the pharmaceutical product for an indication not approved by the United States Food and Drug Administration;

(B)  the product was used as recommended, promoted, or advertised;  

Michigan 600.2946

(5) In a product liability action against a manufacturer or seller, a product that is a drug is not defective or unreasonably dangerous, and the manufacturer or seller is not liable, if the drug was approved for safety and efficacy by the United States food and drug administration, and the drug and its labeling were in compliance with the United States food and drug administration’s approval at the time the drug left the control of the manufacturer or seller. However, this subsection does not apply to a drug that is sold in the United States after the effective date of an order of the United States food and drug administration to remove the drug from the market or to withdraw its approval. This subsection does not apply if the defendant at any time before the event that allegedly caused the injury does any of the following:

(a) Intentionally withholds from or misrepresents to the United States food and drug administration information concerning the drug that is required to be submitted under the federal food, drug, and cosmetic act, chapter 675, 52 Stat. 1040, 21 U.S.C. 301 to 321, 331 to 343-2, 344 to 346a, 347, 348 to 353, 355 to 360, 360b to 376, and 378 to 395, and the drug would not have been approved, or the United States food and drug administration would have withdrawn approval for the drug if the information were accurately submitted

http://www.legislature.mi.gov/(S(5z3q41uoys1lzoajegixoc5p))/mileg.aspx?page=GetObject&objectname=mcl-600-2946

As a preliminary point, if any discount was justified arising under Texas 82.007or Michigan 600.2946, it should be minimal in light of the fact that the defendant has neither raised a defense in any individual case (to the best of our knowledge), nor prevailed in such a defense. A small discount might be warranted to allow plaintiffs to avoid the cost of litigating any matter raised by defense in the unlikely event that the defendants are willing to incur the cost of litigating the matter themselves.

Secondly, if any discount arising under Texas 82.007 and Michigan 600.2946 was justified, cases arising under Texas 82.007 would warrant a less significant discount than those arising under Michigan 600.2946, for reasons we will address below.

It is worth noting that the defendants must affirmatively raise a defense under Texas 82.007 or Michigan 600.2946 and doing so may expose their clinical trials, communications with the FDA, (including warning letters related to their advertising, one of which we have included at the end of this document), to discovery and scrutiny they may wish to avoid. Mass Tort Nexus would be interested in any internal communications, as well as third party communications the defendants engaged in related to the death of Arnold Palmer (including communications with his family) as we have long held the opinion that Xarelto may have caused or contributed to the death of Xarelto’s most famous spokesperson.

Comment: Texas 82.007, does not require a showing that any information that may have been withheld or misrepresentation made to the FDA was “intentional.” Texas 82.007 does not require a plaintiff to plead nor show that the FDA would, and the drug would not have been approved, or the United States Food and Drug Administration would have withdrawn approval for the drug if the information were accurately submitted. Michigan 600.2946, does require plaintiffs to show and plead that any misrepresentations or withholding of information and the drug would not have been approved, or the United States food and drug administration would have withdrawn approval for the drug if the information were accurately submitted.

Michigan 600.2946 obviously places a far more significant burden on a plaintiff seeking to rebut the presumption of immunity than does Texas 82.007. Pleading that a drug would not have been approved, or the United States food and drug administration would have withdrawn approval for the drug if the information were accurately submitted, can be problematic in light of the SCOTUS decision Buckman v. Plaintiff Legal Committee: https://www.loc.gov/item/usrep531341/

The foregoing should not be interpreted as presenting an impossible burden for plaintiffs to overcome under Michigan 600.2946 as was shown in the Second Circuit decision in DESIANO v. WARNER-LAMBERT & CO. https://caselaw.findlaw.com/us-2nd-circuit/1209786.html. Also see TAYLOR v. SMITHKLINE BEECHAM Michigan Supreme Court decision https://caselaw.findlaw.com/mi-supreme-court/1355001.html. These two well-reasoned rulings and opinions make it clear that 1. Plaintiffs can meet the requirements set forth in Michigan 600.2946 to overcome the presumption of immunity without running afoul of Buckman. 2. Plaintiffs can prevail in overcoming a defense raised under Michigan 600.2946 as they did in DESIANO.

Notwithstanding the foregoing, the burden placed un plaintiffs under Michigan 600.2946 is still far greater than that placed on plaintiffs by Texas 82.007.  It appears that any defendant has a better chance of prevailing in raising a defense under Michigan 600.2946 than one raised under Texas 82.007 however, given the fact that Michigan has a population of 9,996,000,(3.05% percent of the U.S. population) while Texas has a population of 27,700,000 (8.45% percent of the U.S. population), would the defendants be willing to undertake the time and expense (and continued concern from the market) involved in raising a defense under Michigan 600.2946, which would not dispose of a significant number of cases, if they prevail given that there is no reason to believe that a disproportionate number of the total Xarelto cases on file arise under Michigan law. Additionally, would the defendant be likely to undertake the time and expense (and continued concern from the market) involved in raising a defense under Texas 82.007, with a far less likelihood of prevailing than in Michigan.

The plaintiff’s burden with overcoming a defense raised under Texas  82.007 is obviously less arduous that than the burden over overcoming a defense raised under Michigan 600.2946. Due to the foregoing, the defendant’s application of the same discount (if any is justified) to cases arising under Texas law to those arising under Michigan Law, is not justified.

 

Michigan and Texas Law and the 11/07/2018 Label Change

Texas 82.007 and Michigan 600.2946:

Texas 82.007: The defendants’ statements in the 11/07/2018 label change “not recommending” these tests are still arguably misleading given that the test apparently have no diagnostic value when a patient is taking Xarelto and more importantly represent important information previously withheld from the FDA and/or mispresenting to the FDA. A strict interpretation of C would not require a plaintiff to show that that the actions or inactions of the defendant were intentional. Arguably, the 11/07/2018 label change related to these tests could be rebut the presumption that the protection provided from Texas 82.007 is available to the defendant.

Michigan 600.2946: The same reasoning applied to the analysis of Texas  82.007 applies to Michigan 600.2946 in this matter with one exception, Michigan 600.2946 requires a showing that the defendants actions or inactions were intentional and a showing that the FDA would not have approved or would have withdrawn the approval for the product if not for the information withheld or misrepresentations made. MTN provides an analysis below aimed at showing what the defendants knew and when they knew it relevant to the warnings they neglected to add to their label until 11/07/2018.

Analysis

The following analysis is more relevant to Michigan 600.2946 than to Texas 82.007. There is a high degree of confidence that Plaintiffs would prevail in any defense raised under Texas 82.007.

In that overcoming a defense raised under Michigan 600.2946 requires a showing that the defendant intentionally made misrepresentations the FDA or intentionally withheld information from the FDA. Additionally, under Michigan 600.2946   plaintiffs must make a colorable argument that the FDA would not have approved the drug or would have later withdrawn approval, absent the misrepresentations or withheld information. The 11/07/2018 FDA label change related to anticoagulant testing would be an example of evidence plaintiffs might present to meet the requirements of Michigan 600.2946. In that Michigan’s law require plaintiffs show the offending actions or inactions of the defendant were intentional, demonstrating what the defendants knew (relevant to the referenced anticoagulation tests) and when they knew it would be important in overcoming a defense raised under Michigan 600.2946.

It should be noted that a defense raised under Michigan 600.2946 or Texas 82.007 exposes the defendant to broad discovery, through which plaintiffs would likely discover far more evidence to support their rebuttal arguments than can be discovered in the public domain.  For our instant purpose however, we will focus on determining when the defendant knew or should have known that the anticoagulation tests listed in the 11/07/2018 label change provide no diagnostic value for patients on Xarelto.

Mass Tort Nexus has conducted a review of the publicly available literature in order to establish what the defendant knew or should have know and when, related to anticoagulation testing with commonly used modalities and methods. We will not present a chronological listing (not exhaustive) of information in the public domain relevant to this topic.

 It should be noted that any information or data published in clinical literature must be developed over time (before it is reported). We can safely assume that any information reported in the medical literature in 2012 was known to the defendant at the time they sought the initial FDA approval for Xarelto, granted in July of 2011. If the defendants were to raise a defense under Michigan 600.2946 or Texas 82.007, plaintiffs would likely be allowed broad discovery which would reveal that the defendants possessed or should have possessed the information related to anticoagulation tests that they withheld from the FDA and prescribing physicians until 11/07/2018.

 No Exhaustive Review of the Literature

2012

The data below was taken from a presentation from Ohio Society of Pharmacist Association in 2012. Given the fact that the information below was reliant on clinical observations prior to the presentation of the below, it is likely that the defendant was aware of the issue related to INR testing, prior to seeking U.S. FDA approval (granted July 1, 2011)

Summary
• Dabigatran
– aPTT
• Appears to be a useful measure in hemorrhagic emergency
• Therapeutic ranges have not yet been established
– Ecarin clotting time
• Also useful in hemorrhagic emergency, but not widely available.
• Rivaroxaban and Apixaban
– Prothrombin time, but not INR
• Appears to be useful in hemorrhagic emergency
• Therapeutic ranges have not yet been established
– HepTest, PiCT, and chromagenic assay all appear to be
useful, but not commonly available

https://cdn.ymaws.com/www.ohioshp.org/resource/resmgr/annualmeetinghandouts/effects_of_new_oral_anticoag.pdf

 May 2012

Rivaroxaban: Quantification by anti-FXa assay and influence on coagulation tests: a study in 9 Swiss laboratories.

RXA plasma levels can be quantified accurately and precisely by a chromogenic anti-FXa assay on different coagulometers in different laboratories. Ingestion of 10mg RXA results in significant alterations of both PT- and aPTT-based coagulation assays.

https://www.ncbi.nlm.nih.gov/pubmed/21840043?dopt=Abstract

July 2012 Rivaroxaban: A practical Guide

INR testing should be preformed just before the next intake of Rivaroxaban on the INR measurement

http://www.uclmontgodinne.be/files/RivaroxabanPracticalGuide06072012.pdf

Thrombosis Journal 2013

https://thrombosisjournal.biomedcentral.com/articles/10.1186/1477-9560-11-11

Because rivaroxaban and other target-specific oral anticoagulants have different mechanisms of action from traditional anticoagulant agents, laboratory tests used for these traditional agents (such as PT/international normalized ratio [INR] or activated partial thromboplastin time) are not suitable for target-specific oral anticoagulants

Pub Med   May 2017

https://www.ncbi.nlm.nih.gov/pubmed/28476405

Direct factor Xa inhibitors such as rivaroxaban or apixaban may prolong prothrombin time (PT) and elevate international normalized ratio (INR). However, these tests are not reliable for assessing the anticoagulation effects of these agents such as rivaroxaban or apixaban may prolong prothrombin time (PT) and elevate international normalized ratio (INR). However, these tests are not reliable for assessing the anticoagulation effects of these agents.

See the warning letter sent from the FDA to the makers of Xarelto. Mass Tort Nexus believes more warning letters like this one exist and will continue our efforts to discover all relevant FDA communications. This warning letter is highly relevant to the prior subject matter of this article.

(FDA Link to June 6, 2013 Warning Letter to Johnson & Johnson Re: Xarelto Label is Below)

NDA 202439 XARELTO (rivaroxaban) tablets   

June 6, 2013

Johnson & Johnson International, Inc.

 

 

______________________________________________________________________________________________________

 

 

Food and Drug Administration

Silver Spring, MD 20993

Roxanne McGregor-Beck, Director

Johnson & Johnson International, Inc.

1000 Route 202 South

P.O. Box 300

Raritan, New Jersey 08869-0602

 

RE: NDA #202439

XARELTO (rivaroxaban) tablets

MA #215

Dear Ms. McGregor-Beck:

The Office of Prescription Drug Promotion (OPDP) of the U.S. Food and Drug Administration (FDA) has reviewed a direct-to-consumer (DTC) print advertisement (K02XS121040 AF) (Print Ad) for XARELTO (rivaroxaban) tablets (Xarelto) submitted by Johnson & Johnson International, Inc. (Johnson & Johnson) on behalf of Janssen Pharmaceuticals, Inc. under cover of Form FDA 2253 and observed during routine surveillance in the January/February 2013 issue of WebMD magazine. The Print Ad is false or misleading because it minimizes the risks associated with Xarelto and makes a misleading claim. Thus, the Print Ad misbrands Xarelto in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 352(n) and FDA implementing regulations. 21 CFR 202.1(e)(5)(i); (e)(7)(viii), (ix).

Background:

Below is the indication and summary of the most serious and most common risks associated with the use of Xarelto.1 According to its FDA-approved product labeling (PI), in pertinent part:

Xarelto is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

There are limited data on the relative effectiveness of XARELTO and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well controlled.

 The PI for Xarelto contains Boxed Warnings regarding increased risk of stroke after discontinuation in patients with nonvalvular atrial fibrillation and the risk of spinal/epidural

hematoma. The PI also contains Contraindications regarding active pathological bleeding and severe hypersensitivity reaction to Xarelto, as well as Warnings and Precautions regarding the risk of bleeding, use in patients with renal impairment and hepatic impairment, use with P-gp and strong CYP3A4 inhibitors or inducers, and risk of pregnancy related hemorrhage. The most common adverse reactions with Xarelto were bleeding complications.

Minimization of Risk Information

 Promotional materials are false or misleading if they fail to present risks associated with a drug with a prominence and readability reasonably comparable with the presentation of information relating to the benefits of the drug. Factors impacting prominence and readability include typography, layout, contrast, headlines, paragraphing, white space, and other techniques apt to achieve emphasis. The Print ad prominently presents various efficacy claims for Xarelto, such as, but not limited to, the following, that are presented in large, bolded and/or colorful text and graphics (emphasis original):

• “If you have atrial fibrillation (AFib)”

• “Ready to break your AFib routine?”

• “XARELTO® is the first and only once-a-day prescription blood thinner for patients with AFib not caused by a heart valve problem, that is proven to reduce

the risk of stroke—without routine blood monitoring.”

• “…With XARELTO®, there’s no routine blood monitoring—so you have more time for yourself. There are no dietary restrictions, so you’re free to enjoy the healthy foods you love. And there are no dosage adjustments, which means you can manage your risk with just one pill a day, taken with your evening meal. Learn how XARELTO® can help simplify your AFib-related stroke risk treatment….”

In contrast, the risk information is presented on the preceding adjacent page without any of the emphasis (i.e. color scheme, borders, layout, and graphics) used with the efficacy claims. The result is a presentation which appears unconnected to the efficacy claims and is therefore not likely to draw readers’ attention. This overall presentation misleadingly  minimizes the risks associated with Xarelto because it fails to convey this important risk information with a prominence and readability reasonably comparable to the efficacy claims. We note that the Print Ad contains the statement, “Please see accompanying Medication Guide on the following pages” (emphasis original) at the bottom of the page, and that risk information is presented on an adjacent page, but this is not sufficient to mitigate the overall misleading presentation.

Misleading Claim

 The Print Ad includes the following claim (emphasis original):

• “And there are no dosage adjustments…”

The above claim misleadingly suggests that dosage adjustments are not necessary with Xarelto. However, according to the DOSAGE AND ADMINISTRATION section of the PI, the dose should be lowered to 15 mg once daily for patients with renal impairment who may have a CrCL of 15 to 50 mL/min. In addition, the WARNINGS AND PRECAUTIONS section of the PI states, “…Periodically assess renal function as clinically indicated…and adjust therapy accordingly….” Thus, patients with renal impairment may need to have their dosage adjusted while on Xarelto therapy.

Conclusion and Requested Action

For the reasons discussed above, the Print Ad misbrands Xarelto in violation of the FD&C Act, 21 U.S.C. 352(n) and FDA implementing regulations. 21 CFR 202.1(e)(5)(i); (e)(7)(viii), (ix). OPDP requests that Johnson & Johnson immediately cease the dissemination of violative promotional materials for Xarelto such as those described above. Please submit a written response to this letter on or before June 20, 2013, stating whether you intend to comply with this request, listing all promotional materials (with the 2253 submission date) for Xarelto that contain violations such as those described above, and explaining your plan for discontinuing use of such violative materials.

Please direct your response to the undersigned at the Food and Drug Administration,

Center for Drug Evaluation and Research, Office of Prescription Drug Promotion, 5901-B Ammendale Road, Beltsville, Maryland 20705-1266 or by facsimile at (301) 847-8444. To ensure timely delivery of your submissions, please use the full address above and include a prominent directional notation (e.g. a sticker) to indicate that the submission is intended for OPDP. Please refer to MA# 215 in addition to the NDA number in all future correspondence relating to this particular matter. OPDP reminds you that only written communications are considered official. The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for Xarelto comply with each applicable requirement of the FD&C Act and FDA implementing regulations.

Sincerely,

{See appended electronic signature page}

Zarna Patel, Pharm.D.

Regulatory Review Officer

Office of Prescription Drug Promotion

{See appended electronic signature page}

Amy Toscano, Pharm.D., RAC, CPA

Team Leader

Office of Prescription Drug Promotion

 

Read More

Xarelto Settlement: Dead on Arrival?

April 15, 2019

(Mass Tort Nexus Media) Bayer and Johnson & Johnson both issued press releases on March 25th indicating to the public, as well as stockholders and analysts, that the companies had reached a settlement to resolve approximately 25,000 claims related to Xarelto. This announcement was arguably highly misleading, in that the agreement reached has not actually resulted in the settlement of a single Xarelto lawsuit (to the best of our knowledge) and certainly not 25,000 cases.

This was the headline in Reuters:  Bayer, J&J settle U.S. Xarelto litigation for $775 million,see Reuters.com/article/us-bayer-xarelto/bayer-jj-settle-us-xarelto-litigation-for-$775-million

At the time of press release, in which Bayer and Johnson & Johnson led the public and the market to believe they had resolved (settled) 25,000 pending Xarelto lawsuits, the overwhelming majority of firms representing those 25,000 clients had yet to receive significant details related to the proposed settlement, and of course had yet to present any offer to their individual clients, who would have to accept any offer made before a case could actually be settled.

Law Firms attending the Mass Torts Made Perfect conference in Las Vegas last week received more details related to the defendants proposed settlement and the reaction was not positive.

Large Scale Rejection of Proposed Settlement?

Mass Tort Nexus has spoken with a great a number of firms who were in attendance at MTMP, as well as numerous others since that time, and the clear indication that we have received would lead us to the conclusion that it is highly unlikely that the defendants proposed settlement will be accepted by enough firms (or rather their clients), to make going forward with the current proposed settlement anything other than a waste of time.

Law Firms that have been in contact with Mass Tort Nexus have indicated that they will fulfill their duty to present any offer made by defendants for their cases to the individual clients; however, they will not likely recommend that clients accept the offers made under the proposed settlement scheme. Many of the firms made colorful comments that we will not publish; however, there was a common theme among the comments:

“I would feel like I was selling out my clients if I recommend they accept the current offer the defendants have made.”

Others went as far as to say:

“I think it would be malpractice to recommend that clients accept the final amounts likely to be offered in this settlement scheme”

Dilemma for Bayer and Johnson & Johnson

The premature and arguably misleading public announcement, which would likely be considered official stock holder guidance, may create additional problems for the corporations already plagued by legal woes, which pose risks to their respective stock prices and stock holder value. If the proposed Xarelto settlement does fall through, as it appears will likely be the case, the companies will be faced with having to walk back previous positive news  “We have resolved the risk associated with the Xarelto litigation” to “not only have we not resolved the risk associated with the Xarelto litigation, but that risk may now be more significant than it was before we proposed a settlement, and many plaintiffs firms see it as more of an insult than an offer.”

If the proposed settlement was even close to something plaintiffs might except in significant numbers, Bayer and J&J might have been in a position to “tweak the settlement” and avoid having to deliver bad news to their stockholders and the public. Unfortunately for Bayer and J&J, the proposed settlement seems to be so far from “acceptable” that their only option may be to scrap the current proposed settlement and come back with another proposal, that will not be received with such strong resistance. If the two corporate giants have any hope of salvaging their messaging to the market, they will need to act quickly.

Proposed Settlement Appears to be a “Non-Starter” 

      

For now, it appears that there is no amount of lipstick that would make the proposed Xarelto settlement scheme attractive.  Most of the firms Mass Tort Nexus has spoken to have indicated that the defendants offer is not even a starting point.

 

 

 

 

MTN will provide more information in future articles about the proposed settlement, as well as the reasons a large number of firms do not feel the settlement is fair and just to their clients. At this point in time; however, it seems likely that the proposed Xarelto settlement is:

The Industry Comment

       XARELTO SETTLEMENT

Read More

Why Didn’t Bayer’s October 2018 Forecast Include Monsanto Roundup Litigation MDL 2741? Several billion possible reasons!

By Mark A. York (March 25, 2019)

Jury Verdict Forms of March 19, 2019 Trial Findings Re: “Monsanto Roundup Caused Plaintiff’s Cancer”

Roundup MDL 2741 Federal Trial Jury Instructions of March 19, 2019

Roundup MDL 2741 Federal Trial Jury Verdict Form of March 19, 2019

 

Interim Report Third Quarter 2018

 

Explanatory Notes

Legal Risks

Product-related litigation

Mirena™: As of January 30, 2018, lawsuits from approximately 2,900 users of Mirena™, a levonorgestrel-releasing intrauterine system providing long-term contraception, had been served upon Bayer in the United States (excluding lawsuits no longer pending). Plaintiffs allege personal injuries resulting from the use of Mirena™, including perforation of the uterus, ectopic pregnancy or idiopathic intracranial hypertension, and seek compensatory and punitive damages. Plaintiffs claim, inter alia, that Mirena™ is defective and that Bayer knew or should have known of the risks associated with it and failed to adequately warn its users. Additional lawsuits are anticipated. In April 2017, most of the cases pending in U.S. federal courts in which plaintiffs allege idiopathic intracranial hypertension were consolidated in a multidistrict litigation (“MDL”) proceeding for common pre-trial management. As of January 30, 2018, lawsuits from approximately 400 users of Mirena™ alleging idiopathic intracranial hypertension had been served upon Bayer in the United States. Another MDL proceeding concerning perforation cases has, in the meantime, been dismissed. The Second Circuit Court of Appeals affirmed the perforation MDL district court’s summary judgment order of 2016 dismissing approximately 1,230 cases pending before that court. In August 2017, Bayer reached an agreement in principle with plaintiffs’ counsel leadership for global settlement of the perforation litigation, for a total amount of US$12.2 million. As of January 30, 2018, a total of approximately 4,000 cases would be included in the settlement. The idiopathic intracranial hypertension MDL proceeding is not included in the settlement.

As of January 30, 2018, five Canadian lawsuits relating to Mirena™ seeking class action certification had been served upon Bayer. Bayer believes it has meritorious defenses and intends to defend itself vigorously.

        XARELTO LITIGATION

Xarelto™: As of January 30, 2018, U.S. lawsuits from approximately 22,000 recipients of Xarelto™, an oral anticoagulant for the treatment and prevention of blood clots, had been served upon Bayer. Plaintiffs allege personal injuries from the use of Xarelto™, including cerebral, gastrointestinal or other bleeding and death, and seek compensatory and punitive damages. They claim, amongst other things, that Xarelto™ is defective and that Bayer knew or should have known of these risks associated with the use of Xarelto™ and failed to adequately warn its users. Additional lawsuits are anticipated. Cases pending in U.S. federal courts have been consolidated in an MDL for common pre-trial management. In May, June and August 2017, the first three MDL trials resulted in complete defense verdicts; plaintiffs have appealed all three verdicts. In January 2018, after the first trial to proceed in Pennsylvania state court had initially resulted in a judgment in favor of the plaintiff, the trial judge vacated the jury’s verdict and granted judgment in favor of Bayer. Further Pennsylvania state court trials are currently scheduled for the first and second quarters of 2018. Bayer anticipates that additional trials will be scheduled.

As of January 30, 2018, ten Canadian lawsuits relating to Xarelto™ seeking class action certification had been served upon Bayer. Bayer believes it has meritorious defenses and intends to defend itself vigorously.

Essure™: As of January 30, 2018, U.S. lawsuits from approximately16,100 users of Essure™, a medical device offering permanent birth control with a nonsurgical procedure, had been served upon Bayer. Plaintiffs allege personal injuries from the use of Essure™, including hysterectomy, perforation, pain, bleeding, weight gain, nickel sensitivity, depression and unwanted pregnancy, and seek compensatory and punitive damages. Additional lawsuits are anticipated.

As of January 30, 2018, two Canadian lawsuits relating to Essure™ seeking class action certification had been served upon Bayer. Bayer believes it has meritorious defenses and intends to defend itself vigorously.

Class actions over neonicotinoids in Canada: Proposed class actions against Bayer were filed in Quebec and Ontario (Canada) concerning crop protection products containing the active substances imidacloprid and clothianidin (neonicotinoids). Plaintiffs are honey producers, who have filed a proposed nationwide class action in Ontario and a Quebec-only class action in Quebec. Plaintiffs claim for damages and punitive damages and allege Bayer and another crop protection company were negligent in the design, development, marketing and sale of neonicotinoid pesticides. The proposed Ontario class action is in a very early procedural phase. In Quebec, the plaintiff sought authorization (certification) of a class for which a motion was heard in November 2017. Bayer believes it has meritorious defenses and intends to defend itself vigorously.

INSURANCE COMPANY PAYS THE BILLS

In connection with the above-mentioned proceedings, Bayer is insured against statutory product liability claims against Bayer to the extent customary in the respective industries and has, based on the information currently available, taken appropriate accounting measures for anticipated defense costs. However, the accounting measures relating to Essure™ claims exceed the available insurance coverage.

SHOULD BAYER HAVE INSERTED ROUNDUP MDL LITIGATION HERE?

https://www.masstortnexus.com/News/4362/Monsanto-Bayer-Facing-Over-11-000-Lawsuits-Over-Roundup-Cancer-Risk-As-New-Federal-Trial-Starts

Link to US District ND California Monsanto MDL 2741 litigation case outline and case related orders: https://www.cand.uscourts.gov/VC/roundupmdl

[End of Bayer-Mosanto Docket in MDL 2741]

March 6, 2019 https://www.masstortnexus.com/mass-torts-news/bayer-ag-completes-monsanto-purchase-whats-next-on-litigation-dockets/

Patent Disputes

Adempas™: In January 2018, Bayer filed patent infringement lawsuits in a U.S. federal court against Alembic Pharmaceuticals Limited, Alembic Global Holding SA, Alembic Pharmaceuticals, Inc. and INC Research, LLC (together “Alembic”), against MSN Laboratories Private Limited and MSN Pharmaceuticals Inc. (together “MSN”) and against Teva Pharmaceuticals USA, Inc. and Teva Pharmaceutical Industries Ltd. (together “Teva”). In December 2017, Bayer had received notices of an Abbreviated New Drug Application with a paragraph IV certification (“ANDA IV”) pursuant to which Alembic, MSN and Teva each seek approval of a generic version of Bayer’s pulmonary hypertension drug Adempas™ in the United States.

Betaferon™ / Betaseron™: In 2010, Bayer filed a complaint against Biogen Idec MA Inc. in a U.S. federal court seeking a declaration by the court that a patent issued to Biogen in 2009 is invalid and not infringed by Bayer’s production and distribution of Betaseron™, Bayer’s drug product for the treatment of multiple sclerosis. Biogen is alleging patent infringement by Bayer through Bayer’s production and distribution of Betaseron™ and Extavia™ and has sued Bayer accordingly. Bayer manufactures Betaseron™ and distributes the product in the United States. Extavia™ is also a drug product for the treatment of multiple sclerosis; it is manufactured by Bayer, but distributed in the United States by Novartis Pharmaceuticals Corporation, another defendant in the lawsuit. In 2016, the U.S. federal court decided a disputed issue regarding the scope of the patent in Biogen’s favor. Bayer disagrees with the decision, which may be appealed at the conclusion of the proceedings in the U.S. federal court.

Damoctocog alfa pegol (BAY 94‑9027, long-acting recombinant factor VIII): In August 2017, Bayer filed a lawsuit in a U.S. federal court against Nektar Therapeutics (“Nektar”), Baxalta Incorporated and Baxalta U.S., Inc. (together “Baxalta”) seeking a declaration by the court that a patent by Nektar is invalid and not infringed by Bayer’s drug candidate BAY 94‑9027 for the treatment of hemophilia A. In September 2017, Baxalta and Nektar filed a complaint in a different U.S. federal court against Bayer alleging that BAY 94‑9027 infringes seven other patents by Nektar. Regarding the complaint by Bayer, Nektar and Baxalta gave Bayer a covenant not to make any claims against Bayer for infringement of that patent. Bayer amended the complaint to now seek a declaration by the court that the seven other patents by Nektar are not infringed by BAY 94‑9027. The patents are part of a patent family registered in the name of Nektar and further comprising European patent applications with the title “Polymer-factor VIII moiety conjugates” which are at issue in a lawsuit Bayer filed against Nektar in 2013 in the district court of Munich, Germany. In this proceeding, Bayer claims rights to the European patent applications based on a past collaboration between Bayer and Nektar in the field of hemophilia. However, Bayer believes that the patent family does not include any valid patent claim relevant for Bayer’s drug candidate BAY 94‑9027 for the treatment of hemophilia A.

Nexavar™: In 2015, Bayer filed patent infringement lawsuits in a U.S. federal court against Mylan Pharmaceuticals Inc. and Mylan Inc. (together “Mylan”). In 2014 and 2015, Bayer had received notices of an ANDA IV application pursuant to which Mylan seeks approval of a generic version of Bayer’s cancer drug Nexavar™ in the United States. In October 2017, Bayer reached agreement with Mylan to settle this patent dispute. Under the settlement terms, Mylan will obtain a license to sell its generic version of Nexavar™ in the United States at a date after the expiration of the patent for the active ingredient expiring in January 2020. In 2016, Bayer had received another notice of such an ANDA IV application by Teva Pharmaceuticals USA, Inc. Bayer filed a patent infringement lawsuit against Teva in the same U.S. federal court. In January 2018, Bayer reached agreement with Teva to settle this patent dispute. Under the settlement terms, Teva will obtain a license to sell its generic version of Nexavar™ in the United States at a date after the expiration of the patent for the active ingredient expiring in January 2020.

Stivarga™: In 2016, Bayer filed patent infringement lawsuits in a U.S. federal court against Apotex, Inc. and Apotex Corp. (together “Apotex”) and against Teva. Bayer had received notices of an ANDA IV application pursuant to which Apotex and Teva each seek approval of a generic version of Bayer’s cancer drug Stivarga™ in the United States.

Xarelto™: In 2015, Bayer and Janssen Pharmaceuticals filed a patent infringement lawsuit in a U.S. federal court against Aurobindo Pharma Limited, Aurobindo Pharma USA, Inc. (together “Aurobindo”), Breckenridge Pharmaceutical Inc. (“Breckenridge”), Micro Labs Ltd., Micro Labs USA Inc. (together “Micro Labs”), Mylan, Prinston Pharmaceutical Inc. (“Prinston”), Sigmapharm Laboratories, LLC (“Sigmapharm”), Torrent Pharmaceuticals, Limited and Torrent Pharma Inc. (together “Torrent”). Bayer had received notices of an ANDA IV application by Aurobindo, Breckenridge, Micro Labs, Mylan, Prinston, Sigmapharm and Torrent, each seeking approval to market a generic version of Xarelto™, an oral anticoagulant for the treatment and prevention of blood clots, in the United States. In 2016, Bayer received another notice of such an ANDA IV application by InvaGen Pharmaceuticals, Inc. (“InvaGen”). Bayer and Janssen Pharmaceuticals filed a patent infringement lawsuit against InvaGen in the same U.S. federal court.

Bayer believes it has meritorious defenses in the above ongoing patent disputes and intends to defend itself vigorously.

Further Legal Proceedings

Trasylol™ / Avelox™: A qui tam complaint relating to marketing practices for Trasylol™ (aprotinin) and Avelox™ (moxifloxacin) filed by a former Bayer employee is pending in the United States District Court in New Jersey. The U.S. government has declined to intervene at the present time.

Newark Bay Environmental Matters: In the United States, Bayer is one of numerous parties involved in a series of claims brought by federal and state environmental protection agencies. The claims arise from operations by entities which historically were conducted near Newark Bay or surrounding bodies of water, or which allegedly discharged hazardous waste into these waterways or onto nearby land. Bayer and the other potentially responsible parties are being asked to remediate and contribute to the payment of past and future remediation or restoration costs and damages. In 2016, Bayer learned that two major potentially responsible parties had filed for protection under Chapter 11 of the U.S. Bankruptcy Code. While Bayer remains unable to determine the extent of its liability for these matters, this development is likely to adversely affect the share of costs potentially allocated to Bayer.

In the Lower Passaic River matter, a group of more than sixty companies including Bayer is investigating contaminated sediments in the riverbed under the supervision of the United States Environmental Protection Agency (EPA) and other governmental authorities. Future remediation will involve some form of dredging, the nature and scope of which are not yet defined, and potentially other tasks. The cost of the investigation and the remediation work may be substantial if the final remedy involves extensive dredging and disposal of impacted sediments. In the Newark Bay matter, an unaffiliated party is currently conducting an investigation of sediments in Newark Bay under EPA supervision. The investigation is in a preliminary stage. Bayer has contributed to certain investigation costs in the past and may incur costs for future investigation and remediation activities in Newark Bay.

Bayer has also been notified by governmental authorities acting as natural resource trustees that it may have liability for natural resource damages arising from the contamination of the Lower Passaic River, Newark Bay and surrounding water bodies. Bayer is currently unable to determine the extent of its liability.

Asbestos: A further risk may arise from asbestos litigation in the United States. In many cases, the plaintiffs allege that Bayer and co-defendants employed third parties on their sites in past decades without providing them with sufficient warnings or protection against the known dangers of asbestos. Additionally, a Bayer affiliate in the United States is the legal successor to companies that sold asbestos products until 1976. Union Carbide has agreed to indemnify Bayer for this liability. Bayer believes it has meritorious defenses and intends to defend itself vigorously.

There is no official reference to Monsanto Roundup MDL 2741, even though an August 2018 verdict award for the plaintiff in California State Court was for more than $280 million, and showed that non-hodgkins lymphoma was caused by use of Monsanto Roundup herbicide containing Glyphosate. f

https://www.reuters.com/article/us-bayer-glyphosate-lawsuit/bayer-shares-slide-after-latest-roundup-cancer-ruling-idUSKCN1R02O3

 

Bayer legal Disclaimer October 2018: Cautionary Statements Regarding Forward-Looking Information

Certain statements contained in this communication may constitute “forward-looking statements.” Actual results could differ materially from those projected or forecast in the forward-looking statements. The factors that could cause actual results to differ materially include the following: the risk that the parties may be unable to achieve expected synergies and operating efficiencies in the merger within the expected timeframes (or at all) and to successfully integrate the operations of Monsanto Company (“Monsanto”) into those of Bayer Aktiengesellschaft (“Bayer”); such integration may be more difficult, time-consuming or costly than expected; revenues following the transaction may be lower than expected; operating costs, customer loss and business disruption (including difficulties in maintaining relationships with employees, customers, clients or suppliers) may be greater or more significant than expected following the transaction; the retention of certain key employees at Monsanto; the parties’ ability to meet expectations regarding the accounting and tax treatments of the merger; the impact of refinancing the loans taken out for the transaction; the impact of indebtedness incurred by Bayer in connection with the transaction and the potential impact on Bayer’s rating of indebtedness; the effects of the business combination of Bayer and Monsanto, including the combined company’s future financial condition, operating results, strategy and plans; other factors detailed in Monsanto’s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (the “SEC”) for the fiscal year ended August 31, 2017, and Monsanto’s other filings with the SEC, which are available at http://www.sec.gov and on Monsanto’s website at www.monsanto.com; and other factors discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. Bayer assumes no obligation to update the information in this communication, except as otherwise required by law. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof.

BAYER LITIGATION DOCKETS IN MDL’s ARE STILL GROWING

ROUNDUP-MONSANTO-(GLYPHOSATE)-MDL-2741-(USDC-ND-California) Mass Tort Nexus Briefcase

 

XARELTO-(rivaroxaban)-MDL-2592-(USDC-ED-Louisiana) Mass Tort Nexus Briefcase

 

XARELTO-Case-No-2349–Philadephia-Court-of-Common-Pleas-Complex-Litigation-(PA-State-Court) Mass Tort Nexus Briefcase)

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XARELTO RECENT LABEL CHANGE: Is Rat Poison Safer?

A WHITE PAPER REPORT BY MASS TORT NEXUS

(The following information and conclusions are based on opinions formed after a review of relevant facts and data by John Ray and edited by Lisa Powell, Mass Tort Nexus www.masstortnexus.com)

XARELTO LABEL CHANGE AND CLINICAL TRIAL BACKGROUND

On October 11, 2018, Janssen Pharmaceuticals, Inc. (a division of Johnson & Johnson) changed its Xarelto® drug safety label as follows:

Monitoring for the anticoagulation effect of rivaroxaban using a clotting test (PT, INR or aPTT) for anti-factor XA (FXa) activity is not recommended.

Rivaroxaban is an anticoagulant medication. Anticoagulants thin blood. Rivaroxaban is sold under its trade name, Xarelto®. Xarelto® is used to prevent and/or treat blood clots that could result in strokes in patients with non-valvular atrial fibrillation, in patients undergoing knee and hip reconstruction or replacement surgery, and for secondary prevention in patients who have had an Acute coronary syndrome event.

Prior to FDA approval in 2011, clinical trials were conducted to test the safety and efficacy of Xarelto® and to compare it to other anticoagulants. Trial administrators measured both the medication’s effectiveness in thinning the blood and how long it took to be within the therapeutic range. A blood test is used to measure the international randomized ratio (INR). The INR was used to determine the appropriate dose and dosage (i.e., amount and rate of administration) specific to each patient; or, in this case, each trial participant.

The safety label update made last week by the drug maker, Janssen Pharmaceuticals, Inc. (a division of Johnson & Johnson) in effect states that the INR test used to gain FDA approval—and that doctors continue to use to dose and monitor the effects of Xarelto® in their patients—is arguably defective. Not only would this render the clinical trial results invalid but also bolster plaintiffs’ new and existing claims that the drug maker(s) failed to adequately inform doctors that there was no means by which to determine the correct dose and dosage for any given patient. Essentially a doctor would have to wait until the patient bleeds out or throws a clot before determining that the patient may not be on the right dose and/or dosage. In other words, the INR test likely has no diagnostic value and is no more effective than a shot in the dark.

Summary of Facts and Subsequent Findings

  • On October 11, 2018, the Xarelto® drug safety label was changed to “not” recommend INR testing to monitor the effects Xarelto® on patients
  • INR testing was used in clinical trials to establish the safety and efficacy of Xarelto® and to compare it to other anticoagulants prior to FDA approval and market release in 2011
  • Title 21 of the U.S. Code of Federal Regulation requires that drug labels include a summary of essential scientific information including a statement of the recommended or usual dosage
  • Results from Xarelto® clinical trials using INR testing are at best, questionable, and at worst, invalid
  • A change to the Xarelto® drug safety label likely indicates that the drug makers failed to adequately warn that there was no means by which to determine correct dosage for any given patient
  • A pharmaceutical product for which correct dose and dosage cannot be established for a given patient is arguably defective in a significant way
  • Physicians that rely on INR testing without knowing that it may render inaccurate results could lead them to incorrectly dose Xarelto® potentially causing significant harm to their patients

Methodology Flaws in the Xarelto Clinical Trials

INR testing was used in the original Xarelto® clinical trials known as the ROCKET-AF and EINSTEIN DVT/PE trials. These trials were paid for by the drug makers—Bayer Healthcare and Janssen Pharmaceuticals, Inc. (a division of Johnson & Johnson). These trials were conducted to establish the safety and efficacy of Xarelto® and to compare it to other anticoagulants.

The following is an excerpt from the EINSTEIN DVT/PE clinical trial results:

EINSTEIN DVT/PE trial design: Randomized, phase 3, multicenter, open-label, parallel group,

active-controlled, event-driven noninferiority studies (EINSTEIN DVT and EINSTEIN PE) with patients receiving XARELTO® at an initial dose of 15 mg twice daily with food for the first 3 weeks, followed by XARELTO® 20 mg once daily with food or enoxaparin 1 mg/kg twice daily for at least 5 days with VKA, then VKA only after target INR (2.0-3.0) was reached. Patients were treated for 3, 6, or 12 months at HCP discretion.

In other words, Xarelto® was administered to trial participants and after a target INR was reached, they received a different anticoagulant—a VKA (i.e., vitamin K antagonist).

Given the drug safety update added to the Xarelto® label by Janssen on October 11, 2018:

Monitoring for the anticoagulation effect of rivaroxaban using a clotting test (PT, INR or aPTT) for anti-factor Xa (FXa) activity is not recommended.

Results from Xarelto® clinical trials using INR testing are at best, questionable, and at worst, invalid.

Thank You for Sharing. Not!

In May 2017—17 months before Janssen changed the Xarelto® label—Clinical Therapeutics, an international peer-reviewed journal, published an article entitled, “International Normalized Ratio Is Significantly Elevated with Rivaroxaban and Apixaban Drug Therapies: A Retrospective Study Published.” An excerpt from the article follows (emphasis added):

Purpose

Direct factor Xa inhibitors such as rivaroxaban or apixaban may prolong prothrombin time (PT) and elevate international normalized ratio (INR). However, these tests are not reliable for assessing the anticoagulation effects of these agents. PT assay sensitivity is relatively weak at therapeutic drug concentrations and is subjected to significant variations depending on the reagent used. Conversion of PT to INR may even increase the variability. We conducted a retrospective cross-sectional study aiming to assess the prevalence and extent of INR elevation in hospitalized patients receiving rivaroxaban or apixaban as part of their home medications and to find out whether other existing factors could elevate INR apart from the drug entity itself. [Emphasis added.]

Methods

The data collected from 218 hospitalized patients׳ charts included PT and INR taken on admission, patients׳ characteristics, laboratory results, other medications regularly used, and coexisting clinical conditions.

Findings

No statistically significant association between INR elevation and the parameters examined was found in our study. INR was significantly elevated in both drug groups (P < 0.001), with 84.2% of rivaroxaban patients and 78.3% of apixaban patients presenting with INR levels above the higher limit of the normal range. Furthermore, INR was significantly higher in the rivaroxaban group than in the apixaban group (P < 0.001).

Implications

Both of the reviewed drugs significantly elevated INR. Moreover, rivaroxaban elevates INR significantly more than apixaban, and there are apparently no other factors affecting INR but the drugs themselves. Larger prospective studies are needed to confirm and clarify the clinical significance of these results.

In that the common tests used to determine the correct administration of Xarelto® are not recommended by the drug maker, how are doctors to determine what dose and dosage of Xarelto® is correct vs. what dose and dosage may render a patient over anticoagulated and more likely to experience severe bleeding, or under anticoagulated, leaving patients more likely to suffer the adverse events Xarelto® is intended to treat?

In other words, doctors have relied on—and may continue to rely on—the test that the makers of Xarelto® now say is not recommended to determine the blood-thinning effects of the drug without knowing that these tests were likely rendering inaccurate results which could lead to their treating patients in a manner likely to cause them significant harm.

If the means to determine the correct dosage to administer to a given patient does not exist, the product is arguably defective. In addition, it would be impossible for a drug maker to comply with the requirements of Title 21, as follows:

21 CFR § 201.56 (a)(1): The labeling must contain a summary of the essential scientific information needed for the safe and effective use of the drug.

21 CFR § 201.100(b)(2): Requires labels for prescription drugs bear a statement of the recommended or usual dosage.

Janssen’s Misleading Advertising Campaign

There are three types of anticoagulants used in the United States. Xarelto® is a direct factor Xa inhibitor type. Benefits claimed by its U.S. manufacturer, Janssen Pharmaceuticals, Inc., include once daily administration of an oral pill, no dietary restrictions, and less testing requirements resulting in fewer blood draws. Warfarin, another type of anticoagulant, is a vitamin K inhibitor.  If a patient’s blood becomes too thin after taking warfarin, vitamin K is administered to reverse its blood-thinning effects (i.e., an antidote or reversal agent). While the INR measurement is an effective test to dose and monitor warfarin in patients, Janssen’s advertising campaign touting less testing requirements for Xarelto® as a benefit is laughable given that the INR test used repeatedly to demonstrate the safety and efficacy of Xarelto® “is not recommended.” Until early 2018—approximately seven years after its market release–Xarelto® did not have a reversal agent, and to date, there is not a “recommended” test for doctors to accurately dose and monitor the effects of Xarelto® in their patients.

In 2014, the FDA required Janssen to add new language to its official warnings and precautions including an update to its “black box” because the test equipment used to measure the INR during clinical trials was deemed faulty. The black box is the strongest and most urgent FDA warning added to an official drug label. The update notifies patients and caregivers about certain risks and potentially dangerous side effects from Xarelto®. A year earlier, the FDA cited Johnson & Johnson for its misleading advertising campaign in contradiction to U.S. laws and regulations.

According to Recall Center, a consumer protection organization:

Since the drug’s release, there have been multiple updates to the label warning users of possible risks. In 2013, the FDA issued a determination letter to Johnson & Johnson advising them that their print advertising published in WebMD magazine earlier that year was misleading. They cited the following deficiencies:

  • Effects of the drug to potential patients were downplayed
  • Efficacy claims appeared to be disassociated from the potential risks
  • Assertions that Xarelto has “no dosage adjustments,” which the FDA noted is inaccurate according to the product information’s section on warnings and precautions, as well as its section on dosage and administration.

Because of these allegations, the FDA declared Johnson & Johnson to be in violation of U.S. laws and regulations that oversee drug marketing. [U.S. Food & Drug Administration. “Letter to Roxanne McGregor-Beck, RE: NDA #202439.” (June 6, 2013) FDA.gov. Accessed Oct. 27, 2014]

According to a 2017 PR Newswire press release published by Business Insider (emphasis added):

Johnson & Johnson (NYSE: JNJ), Janssen Pharmaceuticals and Bayer Healthcare (OTC: BAYRY) are accused of downplaying the risks of taking Xarelto and aggressively marketing the drug as an alternative for warfarin in patients needing blood thinners to reduce the risk of dangerous clots. The companies positioned the drug as more convenient, calling for a once-a-day dose and eliminating the need for regular monitoring of a patient’s blood. However, the lawsuits charge that doctors and patients were not fully informed of the risks.

While Janssen’s Xarelto® advertising campaign claims:

And with XARELTO® you can

  • Spend your time how you want to spend it, with no regular blood monitoring

MISLEADING. A more accurate statement would arguably be:

Regular blood monitoring would be useless because it will not identify whether a patient is under anti-coagulated [i.e. clotting too much] or over anti-coagulated [i.e., bleeding too much].

  • Enjoy a full variety of healthy foods with no known dietary restrictions

TRUE.

  • Know it’s working, with no frequent dosage adjustments

MISLEADING. A more accurate statement would arguably be:

There is no means by which to determine if a dosage adjustment is needed in that the common tests to make such a determination are inaccurate in patients who have been administered Xarelto®.

It bears repeating:

A pharmaceutical product for which correct dosage cannot be established or determined for any given patient is arguably defective in a significant way.

With Testing, Rat Poison Can Be Correctly Dosed for Benefit

There may be no better example of why correctly dosing an anticoagulant is important than warfarin. Warfarin first came into commercial use as a rat poison in 1948. Correctly dosed, warfarin is an effective anticoagulant for humans; incorrectly dosed, warfarin is poison.

Unlike Xarelto®, INR testing is reliable for dosing warfarin. To optimize the therapeutic effect without risking dangerous side effects such as bleeding, close monitoring of the degree of anticoagulation is required. During the initial stage of treatment, the INR is checked daily. Intervals between tests can be lengthened if the patient manages stable therapeutic INR levels on an unchanged warfarin dose. Newer point-of-care testing is available and has increased the ease of INR testing in the outpatient setting. Instead of a blood draw, the new INR point-of-care test involves a simple finger prick.

Therefore, an anticoagulant that cannot be accurately dosed is arguably not as safe as rat poison.

———-

The foregoing is an observation of statistics and data related to Xarelto®. The conclusions contained herein are based on opinions formed by the author after a review of the relevant data. We acknowledge that others could draw differing conclusions and opinions based on the same observations.

 References:

https://www.clinicaltherapeutics.com/article/S0149-2918(17)30242-4/pdf

https://www.recallcenter.com/xarelto/fda-news/

https://markets.businessinsider.com/news/stocks/report-more-than-15-000-adverse-events-linked-to-xarelto-in-2016-1002203317

https://www.xareltohcp.com/dvt-pe/clinical-trials

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XARELTO INITIAL ROCKET & EINSTEIN CLINICAL TRIALS NOW SEEN AS FLAWED: ADD THE MAY 2018 FAILURE OF TWO LATEST BAYER/JANSSEN STUDIES = BAD SCIENCE

Xarelto Study Red Flags Ignored: Why were medical research professionals ignored when red flags were raised over the viability of the Xarelto Rocket AF and Einstein DVT study results? Now the clinical trials for both are considered flawed, and the two most recent studies, the “Commander HF” and “Mariner,” failed to produce clear evidence that Xarelto is able to reduce the rate of blood clots in certain high-risk patients or after an acute decline in their condition.

By Mark A. York (October 23, 2018)

 

 

 

 

 

 

 

 

(MASS TORT NEXUS MEDIA) Xarelto (rivaroxaban) is a prescription blood thinner created by Bayer and Janssen Pharmaceuticals that was approved by the Food and Drug Administration (FDA) in 2011. This drug is an anticoagulant for preventing blood from clotting, often used to treat deep vein thrombosis, atrial fibrillation, pulmonary embolism, stroke, and other conditions.

More than one study has shown Xarelto can cause a higher rate of internal bleeding, than other anticoagulant drugs and until very recently, there was no available “antidote” for stopping internal bleeding in patients taking Xarelto. With warfarin, vitamin K has been shown to stop bleeding but there is no vitamin K “parallel” for people taking Xarelto. For Xarelto, it can take 24 hours for a dose to get out of the body. That means that if internal bleeding starts, the patient may simply have to wait it out and hope it stops on its own.

What The Medical Studies Say About Xarelto?

The FDA has received thousands of adverse event reports regarding Xarelto and medical studies have examined the safety of this drug:

  • New England Journal of Medicine (2011): Published the ROCKET-AF study, which compared Xarelto to Warfarin in patients suffering from atrial fibrillation. This was the biggest clinical trial of this medication and it compared the effects of Xarelto to the effects of a similar drug known as Warfarin in over 14,000 patients. The study concluded that “there was not significant between-group difference in the risk of major bleeding.”
  • Archives of Internal Medicine (2012): The study discussed the risk of uncontrollable bleeding outweighing the benefits for several different blood thinners including Xarelto. The researchers in this study found that there was a tripled risk of bleeding among the patients, who were given the drug, and no improvement in overall survival rates.
  • Institute for Safe Medication Practices (2012): Issued a report based on FDA data from the first quarter of 2012. During this period, the FDA received 356 adverse event reports of Xarelto side effects including “serious, disabling, or fatal injury.” Additionally, 158 reports indicated blood clots were the serious side effect.
  • New England Journal of Medicine (2013): Published the results of the ROCKET study, which found that Xarelto may carry an increased risk of bleeding.
  • Medscape (2013): Xarelto is associated with a higher risk of bleeding in certain patients. It caused a nearly 3-fold increase of the risk of bleeding in “acutely ill patients” and 4-fold increased risk of major bleeding in patients that had “Acute Coronary Syndrome” (ACS).

Drug Makers Failed To Disclose Faulty Device In Xarelto Trials

 Rivaroxaban and the ROCKET AF trial issue chronicles: A closer look at benefit risk profile of the drug.

  • BMJ2016354 doi: https://doi.org/10.1136/bmj.i5131 (Published 28 September 2016)Cite this as: BMJ 2016;354:i5131
  • Study Analysis: There has been a lot of hue and cry over the recent question raised about the ROCKET AF[1] trial for rivaroxaban which was the only trial used by the company for drug approval from USFDA. This is indeed a very important concern as it directly impacts the well-being of the patients who are at the receiving end of this very highly prescribed anticoagulant drug in 2014.[2] The main concern with this whole confusion surrounding the ROCKET AF trial is that the device used for measuring the INR in trial arm of warfarin patient was faulty and gave lower INR values than it should have, leading to over dosing of warfarin and thereby increasing bleeding problems with the same, compared to the trial arm of rivaroxaban. However, there has been a reanalysis done by the ROCKET AF researchers, which again reinforced the prior result database of the trial and which was accepted by FDA as well[3]. In the reanalysis, the US FDA clearly mentioned that the effect of the faulty device results in causing bleeding episodes, both minor and major, was minimal.[4]
  • However, following this reanalysis, not everyone who raised the question in the first place was convinced and there was a demand that the data of the complete ROCKET AF trial should be made public for everyone to assess and understand the risks. But since the trial was done and results released before the principles on responsible clinical trial data sharing came into effect, the parent pharmaceutical company for rivaroxaban refused to share the patient level details, citing concerns on privacy and transparency policy [5].
  • In spite of everything said and written for and against this issue, a simple question arises, regarding the amount of belief, honesty and hard work that goes without questioning when you bring a new chemical entity to the research stage, get it approved and then bring it to market. For this to happen, there have to be maintained a very fine balance between pharmaceutical companies, drug regulatory authorities and marketing people. In this case, after initial suspicions, the drug regulatory authorities have cleared and supported the approval of rivaroxaban after reanalysis and that should have a say, in case we want to continue trust with this process of drug entry into the market.
  • Rivaroxaban has shown its efficacy and safety both in patients who required adequate anticoagulation e.g. those who had atrial fibrillation and underwent cardioversion. There are few other trials where rivaroxaban has performed better or equally good than warfarin in terms of both efficacy and safety [6]. These results lead us to believe that all was not wrong with the ROCKET AF trial results. All these, combined with personal experiences of those physicians who had been using the drug rivaroxaban for the last couple of years with a hugely favorable result clearly imply that the drug rivaroxaban is holding its side strongly in the midst of all the controversies surrounding its approval and efficacy and it is here to stay. Adding a last word to all this discussion is that rivaroxaban will always hold an upper hand compared to warfarin when prescribed because of its very favorable and easy to use once daily dosing. We cannot discard all the positive reports and positive experiences associated with this drug, based on real time data, only because of the question raised by some, and considering the fact that the question had been satisficatorily answered with a re analysis with no change in the result.

What Did Or Didn’t The FDA Do About Xarelto?

  • In July, 2011, the U.S Food and Drug Administration (FDA) initially approved the medicine for sale on the market for a limited group of people. This included people who had knee or hip replacement surgery because they were considered to be at a higher risk of blood clotting. Read the FDA News Release here.
  • In November, 2011, Xarelto was approved for a larger group of people, including people with an abnormal heart rhythm, and was used to prevent stroke. Read further.
  • In June, 2012, an FDA advisory panel voted against approving this medicine for the treatment of acute coronary syndrome.
  • In November, 2012, Xarelto was later approved for general treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) after a fast track regulatory review by the FDA. Read more.
  • October 22, 2014, the FDA issued a recall for approximately 13,500 bottles of Xarelto after receiving a customer complaint about contamination in a sales sample.
  • January 12, 2015 – An antidote may have been discovered by Portola Pharmaceuticals for Xarelto. A late-stage clinical trial of the intravenous medication, andexanet alfa, met its goal of “immediately and significantly” reversing Xarelto.

The approval history for Xarelto was actually pretty controversial. FDA reviewers originally said that they recommended against approval, then there was an FDA advisory committee (independent group of key opinion leaders) and they voted in favor, so the FDA approved the drug. Their concern was with how the Phase III trials were run and whether Xarelto had really proved its efficacy. The tests compared patients on warfarin to patients on Xarelto, but the patients on the warfarin run had poor TTR. That means the patients weren’t well controlled on warfarin to begin with, which skews the data in favor of Xarelto.

During the approval process, Xarelto actually wanted a superiority label, which would say that the drug was better than warfarin and other blood thinners. Because of the concerns with the Phase III data, the FDA only gave them a non-inferior label, which says they’re essentially the same in terms of effectiveness.

The INRatio device was the subject of two FDA warning letters about inaccurate readings just as the trial was starting in 2005 and 2006. In 2014, the device was recalled. The use of the INRatio device may have skewed the results with inaccurate readings, making Xarelto look better in comparison with warfarin.

In a 2017 annual report issued by the Institute for Safe Medication Practices (ISMP), it was stated that oral anticoagulant drugs, including Xarelto (rivaroxaban), showed “unacceptably high risks,” according to two government data sources, the FAERS adverse events reports for 2016 and a new systematic study by the Centers for Disease Control and Prevention (CDC).

Overall, the CDC found in its systematic study that the FDA’s FAERS voluntary reporting underestimates anticoagulant drug-related injuries. The CDC discovered that approximately 228,600 emergency department visits occur each year due to the use of blood thinner drugs, including Xarelto, which is 10 times more than the FAERS total number of voluntary reports.

Xarelto Clinical Trial Red Flags

Controversy Surrounding ROCKET-AF: A Call for Transparency, But Should We Be Changing Practice?

Jason D Matos1 and Peter J Zimetbaum1,,2

Arrhythm Electrophysiol Rev. 2016 May; 5(1): 12–13.

doi:  [10.15420/aer.2016.24.2]

Prior to the emergence of novel oral anticoagulants (NOACS), nearly all patients were prescribed vitamin K antagonists for thromboembolic prophylaxis in non-valvular atrial fibrillation (AF). Rivaroxaban (Xarelto, Bayer/Johnson & Johnson), an oral factor Xa inhibitor, is now one of the most frequently prescribed NOACs used for this indication.1,2

ROCKET-AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), published in the New England Journal of Medicine in 2011, demonstrated the non-inferiority of rivaroxaban compared with warfarin for the primary prevention of stroke or systemic embolism in patients with AF. This double-blinded randomised trial, which included 14,264 patients across 45 countries, also showed no significant difference in the risk of major bleeding between these two groups.3

Rivaroxaban use in AF has become widespread since the publication of this trial and US Food and Drug Administration (FDA) approval. Two additional Factor Xa inhibitors, apixaban and edoxaban, have also been evaluated in similar randomised trials and have demonstrated non-inferiority to warfarin for stroke or systemic embolism prophylaxis in patients with non-valvular AF with no significant difference in major bleeding.4,5

In recent months, the results of ROCKET-AF have come into question after the FDA issued a recall notice for the device used to obtain International Normalised Ratio (INR) measurements in the warfarin control group. The FDA found that lower INR values were seen with the ‘point-of-care’ INRatio Monitor System (Alere) compared with a plasma-based laboratory in patients with certain medical conditions.2 These conditions included abnormal haemoglobin levels, abnormal bleeding and abnormal fibrinogen levels.6Since the FDA recall of this device, there has been widespread concern that falsely low INR readings in ROCKET-AF may have led to warfarin overdosing. Inappropriately high warfarin dosing could have increased bleeding rates in the control group and therefore made the rivaroxaban arm appear falsely favourable.7 This point-of-care device recall also highlighted a lack of transparency of the specifics of devices used in large clinical trials.

In response, the authors from ROCKET-AF released a correspondence in February 2016, citing the FDA recall. They also provided a post hoc analysis of patients who may have been affected by the recall. They found that major bleeding was greater in patients with conditions affected by the recall, but, reassuringly, the bleeding risk was greater in those who were on rivaroxaban and not warfarin.6

Despite this post hoc analysis, concern has arisen regarding the generalisability of ROCKET-AF given the faulty point-of-care INR readings. There has been a call for complete transparency of the data from this trial and a better explanation of the mechanism of the incorrect INR measurements.7

Once published, the data supporting an FDA-approved treatment should be available for independent analysis. One issue is that rivaroxaban was approved in the US prior to 1 January 2014, before a new transparency policy on clinical trial data sharing was approved by the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA).2 Drug companies are refusing to share any data on pharmaceuticals approved before 2014.

A device malfunction in a large clinical trial also should raise concern, especially when that trial has altered clinical practice for millions of patients. On review of Patel et al’s correspondence regarding the point-of-care malfunction, there is inadequate explanation of the mechanism of these faulty readings. Why are they only seen only in patients with abnormal haemoglobin and fibrinogen levels? How inaccurate could the readings be – within 0.1 or 1.0 of a gold standard value? Most alarming is the revelation that the manufacturer had evidence of faulty readings in similar models dating back to 2002.2

Despite legitimate concerns regarding the absence of data transparency and the faulty point-of-care device, rivaroxaban need not be removed from clinical practice for AF patients. In ROCKET-AF, the drug demonstrated non-inferiority to warfarin in preventing thromboembolic events. In addition, data has shown that patients potentially affected by the faulty point-of-care device actually bled more on rivaroxaban than warfarin.6 Therefore, the original risk–benefit ratio presented in ROCKET-AF remains true.

There are other, albeit smaller, randomised trials with shorter follow-up times that compare rivaroxaban and warfarin for thromboembolic prophylaxis.8,9 For example, Cappato et al in 2014, randomised 1,504 patients to show that oral rivaroxaban was non-inferior to warfarin in preventing a composite endpoint of stroke, transient ischaemic attack, peripheral embolism, myocardial infarction and cardiovascular death in patients with AF undergoing cardioversion. Major bleeding rates in the rivaroxaban and warfarin arms were similar (0.6 % versus 0.8 % respectively).8

The prospective observational trial XANTUS (Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation) followed 6.784 patients on rivaroxaban for AF during a mean time of 329 days at 311 different hospitals. Major bleeding occurred in 128 patients (2.1 events/100 patient years) and 43 patients (0.7 events/100 patient years) suffered a stroke. These numbers are more reassuring than those seen in ROCKET-AF, though the patient population had a lower risk profile, with an average CHADS2 score of 2.0 compared with 3.5 in ROCKET-AF.10

To further mitigate concern regarding inaccuracies of bleeding rates in the ROCKET-AF control group, it is helpful to compare bleeding rates in the warfarin arms of the other major NOAC trials. The RE-LY (Randomised Evaluation of Long-Term Anticoagulation Therapy) trial, had a warfarin-arm major bleeding rate of 3.4%/year.11 The ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, had a warfarin-arm major bleeding rate of 3.1%/year.4 The ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial, had a warfarin-arm major bleeding rate of 3.4 %/year.5The warfarin arm of ROCKET-AF had a 3.4 %/year major bleeding rate, comparable to the other studies. Furthermore, the ROCKET-AF patients are known to be at higher risk for stroke and bleeding; their average CHADS2 score was highest among these studies (3.5 compared with 2.1–2.8).3 In addition, ROCKET-AF had a very high percentage of patients with a HAS-BLED score ≥3 (62 %) compared with the other studies (23 % in ARISTOTLE and 51 % in ENGAGE AF-TIMI 48).1214

Several large randomised trials have compared the safety and efficacy of rivaroxaban versus warfarin for venous thromboembolic disease. The warfarin arm of the EINSTEIN-PE trial (Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients with Acute Symptomatic Pulmonary Embolism), which randomised patients with pulmonary embolism to warfarin or rivaroxaban, had a major bleeding rate of 2.2 %. The bleeding rate was lower in the rivaroxaban arm (1.1 %) and notably patients received a higher loading dose of rivaroxaban for the first 3 weeks (15 mg twice daily) compared with the daily 20 mg daily in ROCKET-AF.15

The recent uncertainties surrounding ROCKET-AF demonstrate the need for widespread data transparency for major trials with the capability of so greatly affecting patients’ lives. These are complicated issues both for the companies’ manufacturing products and the clinical trial organisations who carry out these studies and analyse the data. Ultimately the goal of full transparency to allow increased confidence in trial results should be sought. In this instance there is no compelling evidence of imminent danger of excessive bleeding with rivaroxaban. We should take notice of the recent findings, but there is no need to change practice.

What Are Xarelto Side Effects?

The most dangerous Xarelto side effect is uncontrollable bleeding. Blood thinning drugs have also been associated with bleeding complications. Other side effects include:

  • Blood clots
  • Gastrointestinal bleeding
  • Spinal bleeding
  • Intracranial bleeding
  • Epidural bleeding
  • Cerebral bleeding
  • Stroke
  • Difficulty breathing

For Information on Xarelto and other mass torts see:

Michael Brady Lunch will speak on the Xarelto litigation as well as the status of Pradaxa litigation and related issues at the upcoming Mass Tort Nexus “CLE Immersion Course”

November 9 -12, 2018 at The Riverside Hotel in Fort Lauderdale , FL.

For class attendance information please contact Jenny Levine at 954.520.4494 or Jenny@masstortnexus.com.

  • For the most up to date information on all MDL dockets and related mass torts visit  masstortnexus.com and review our mass tort briefcases and professional site MDL briefcases.
  • To obtain our free newsletters that contain real time mass tort updates, visit masstortnexus.com/news and sign up for free access.
  • WWW.MASSTORTNEXUS.COM

REFERNCES CITED IN STUDIES SHOWN ABOVE

 Rivaroxaban and the ROCKET AF trial issue chronicles: A closer look at benefit risk profile of the drug. References:
BMJ 2016354 doi: https://doi.org/10.1136/bmj.i5131 (Published 28 September 2016)Cite this as: BMJ 2016;354:i5131
  1. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365:883-891. Article
    2. Top 50 pharmaceutical products by global sales. PMLiVE, Available here.
    3. FDA analyses conclude that Xarelto clinical trial results were not affected by faulty monitoring device.https://www.fda.gov/Drugs/DrugSafety/ucm524678.htm
    4. ROCKET AF Reanalysis Reviews.http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202439Orig1s000Ro…
    5. Joint EFPIA-PhRMA Principles for Responsible Clinical Trial Data Sharing Become Effective.http://www.efpia.eu/mediaroom/132/43/Joint-EFPIA-PhRMA-Principles-for-Re…
    6. Cappato R, Ezekowitz MD, Klein AL, et al. Rivaroxaban vs vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 2014; 35:3346-3355.

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Controversy Surrounding ROCKET-AF: A Call for Transparency, But Should We Be Changing Practice? References
Jason D Matos1 and Peter J Zimetbaum1,,2 Arrhythm Electrophysiol Rev. 2016 May; 5(1): 12–13.; doi:  [10.15420/aer.2016.24.2]
  1. Kubitza D, Becka M, Wensing G, et al. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939 – an oral, direct Factor Xa inhibitor – after multiple dosing in healthy male subjects. Eur J Clin Pharmacol. 2005;61:873–80. PMID: 16328318. [PubMed]
  2. Cohen D. Rivaroxaban: can we trust the evidence? BMJ. 2016;352:i575. DOI: 10.1136/bmj.i575; PMID: 26843102. [PubMed]
  3. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91. DOI: 10.1056/NEJMoa1009638; PMID: 21830957. [PubMed]
  4. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92. DOI: 10.1056/NEJMoa1107039; PMID: 21870978.[PubMed]
  5. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104. DOI: 10.1056/NEJMoa1310907; PMID: 24251359. [PubMed]
  6. Patel MR, Hellkamp AS, Fox KA, et al. Point-of-care warfarin monitoring in the ROCKET AF Trial. N Engl J Med. 2016;374:785–8. DOI: 10.1056/NEJMc1515842; PMID: 26839968. [PubMed]
  7. Mandrola J. Rivaroxaban: It’s not time to cut the rope, yet. Medscape. 9 February 2016. Available at: www.medscape.com/viewarticle/858648. (accessed 6 May 2016.
  8. Cappato R, Ezekowitz MD, Klein AL, et al. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J. 2014;35:3346–55. DOI: 10.1093/eurheartj/ehu367; PMID: 25182247.[PubMed]
  9. Cappato R, Marchlinski FE, Hohnloser SH, et al. Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J. 2015;36:1805–11. DOI: 10.1093/eurheartj/ehv177; PMID: 25975659. [PMC free article] [PubMed]
  10. Camm AJ, Amarenco P, Haas S, et al. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J. 2016;37:1145–53.DOI: 10.1093/eurheartj/ehv466; PMID: 26330425. [PMC free article] [PubMed]
  11. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51. DOI: 10.1056/NEJMoa0905561; PMID: 19717844.[PubMed]
  12. Sherwood MW, Nessel CC, Hellkamp AS, et al. Gastrointestinal bleeding in patients with atrial fibrillation treated With rivaroxaban or warfarin: ROCKET AF trial. J Am Coll Cardiol. 2015;66:2271–81.DOI: 10.1016/j.jacc.2015.09.024; PMID: 26610874. [PubMed]
  13. Lopes RD, Al-Khatib SM, Wallentin L, et al. Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: a secondary analysis of a randomised controlled trial. Lancet. 2012;380:1749–58. DOI: 10.1016/S0140-6736(12)60986-6; PMID: 23036896. [PubMed]
  14. Eisen A, Giugliano RP, Ruff CT, et al. Edoxaban vs warfarin in patients with nonvalvular atrial fibrillation in the US Food and Drug Administration approval population: An analysis from the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial. Am Heart J. 2016;172:144–51. DOI: 10.1016/j.ahj.2015.11.004; PMID: 26856226. [PubMed]
  15. EINSTEIN-PE Investigators, Buller HR, Prins MH, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287–97. DOI: 10.1056/ NEJMoa1113572. PMID: 22449293. [PubMed]

 

 

 

 

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Pradaxa Federal Court Trial Win: $1.25 million verdict-with punitives of $1 million in death case

Betty Erelene Knight (Deceased), Claude R. Knight   vs. Boehringer Ingelheim Pharmaceuticals, Inc.  Docket No. 3:15-cv-06424; Judge Robert C. Chambers (United States District Court-Southern District of West Virginia)

(MASS TORT NEXUS MEDIA) A federal jury has awarded the family of a deceased West Virginia woman $1.25 million after finding that Boehringer Ingelheim failed to warn of risks associated with its blood thinner Pradaxa, causing her to suffer gastrointestinal bleeding.

The federal trial in Huntington, WV, (US District Court Southern District of West Virginia) awarded $250,000 in compensatory damages to the estate of Betty Erelene Knight and her husband Claude R. Knight, and added $1,000,000 more in punitive damages. The jury added the large punitive award after plaintiff counsel showed that Boehringer Ingelheim engaged in wanton and willful acts in handling of its blockbuster drug Pradaxa, primarily in failing to warn of the risks.

The October 17th plaintiffs’ verdict was the first trial win in the country against Boehringer Ingelheim the German drugmaker, showing that the blockbuster drug is dangerous. The Pradaxa defense team had won three earlier trials for the company, and this verdict on behalf of  the estate of Erelene Knight and her surviving spouse Claude, shows that juries can be convinced of the dangers including fatal risks related to Pradaxa. Mrs. Knight, who was in her 80’s passed away while taking Pradaxa.

She suffered from an irregular heartbeat, a condition that often leads to the development of blood clots, which can travel into the brain and cause a stroke. The plaintiff’s doctor stated that she was at “high risk of stroke.”

Prior to being prescribed Pradaxa, her doctors initially prescribed Coumadin, another prescription blood thinner. Because of the risk of uncontrolled bleeding with this particular drug, the victim required “frequent monitoring” which is what the Pradaxa marketing teams focused on, when meeting with doctors while marketing Pradaxa as a “safer alternative to Coumadin.”  Eventually, the victim grew weary of the inconvenience of such monitoring and learned about Pradaxa, which performs a similar function to Coumadin, from a television commercial.

Her doctor agreed to switch her to Pradaxa, and after about 18 months on the drug, she started to suffer from severe, uncontrolled internal bleeding. At one point she required surgery, which significantly weakened her and set into motion a decline in her health. Within several months of the surgery Erelene Knight passed away. Defense vigorously attempted to point the finger at other health conditions and place blame on anything besides Pradaxa, which failed as the punitive damage award of $1 million showed that the jury clearly saw that Boehringer Ingelheim knew the risks of Pradaxa, yet continued offering the drug without sufficient warnings.

The winning plaintiff trial team consisted of the Childers, Schlueter & Smith Firm and partner  Andy Childers, Neal Moskow of Ury & Moskow, LLC and Yvette Ferrer of Ferrer Poirot & Wansbrough. Congratulations to everyone, as the mass tort world looks forward to additional plaintiff verdicts in the many other Pradaxa cases pending in dockets around the country.

WHAT IS PRADAXA?

·        Pradaxa is an anticoagulant medication used to reduce the risk of stroke and blood clots in patients with non-valvular atrial fibrillation (AF), the most common type of heart rhythm abnormality.

·        The safety and efficacy of Pradaxa were studied in a clinical trial comparing Pradaxa with the anticoagulant warfarin. In the trial, patients taking Pradaxa had fewer strokes than those who took warfarin.1

·        From approval in October 2010 through August 2012, a total of approximately 3.7 million Pradaxa prescriptions were dispensed, and approximately 725,000 patients received a dispensed prescription for Pradaxa from U.S. outpatient retail pharmacies.2

Rulings Prior to Trial

The estate’s lawsuit against Boehringer Ingelheim, focused on Pradaxa’s label, asserting claims that the company knew that “certain blood plasma concentrations of Pradaxa increased the risk of a major bleed without contributing any additional stroke prevention benefit.” This risk was actually disclosed on labels for Pradaxa in Europe, but not the United States at the time of the victim’s care. Boehringer also knew that patients should not take Pradaxa if they also use P-gp inhibitor drugs, which Erelene Knight did. And while the company later altered its label to include this information, it did not directly inform doctors of the risk.

Based on all this, the judge presiding over the case ruled the estate presented sufficient evidence to submit the question of liability for “failure to warn” to the jury. Defense protested that at the relevant time, Pradaxa contained a general warning that the drug “can cause serious and, sometimes, fatal bleeding.” But whether or not this was an “adequate” warning given what BI allegedly knew, but failed to disclose on the original U.S. label, will be for the jury to decide.

How the favorable verdict predicts future trial outcomes in not only Pradaxa cases currently pending around the country, but in the more than 25,000 Xarelto blood thinner cases that are filed in the Xarelto MDL 2592 litigation, see Mass Tort Nexus Briefcase XARELTO-(rivaroxaban)-MDL-2592-USDC-ED-Louisiana (Judge Eldon Fallon), and in the Philadelphia Court of Common Pleas, see XARELTO-Case-No-2349-in-Philadephia-Court-of-Common-Pleas–Complex-Litigation-(PA-State-Court). There are several bellwether trials set for the Philadelphia Xarelto cases in 2019, where Laura Feldman and Rosemary Pinto of the Philadelphi firm of Feldman & Pinto, will be co-lead counsel for the trial team.

Michael Brady Lunch will speak on the Pradaxa litigation as well as the status of Xarelto and related issues at the upcoming Mass Tort Nexus “CLE Immersion Course”

November 9 -12, 2018 at The Riverside Hotel in Fort Lauderdale , FL.

For class attendance information please contact Jenny Levine at 954.520.4494 or Jenny@masstortnexus.com.

For the most up to date information on all MDL dockets and related mass torts visit  www.masstortnexus.com and review our mass tort briefcases and professional site MDL briefcases.

To obtain our free newsletters that contain real time mass tort updates, visit www.masstortnexus.com/news and sign up for free access.

WWW.MASSTORTNEXUS.COM

 

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XARELTO STUDIES FAIL IN BAYER/J&J ATTEMPTS TO EXPAND MARKET CONTROL

THE RECENT FAILURE OF TWO XARELTO STUDIES STOPPED BAYER AND JOHNSON & JOHNSON ATTEMPTS TO INCREASE BLOOD THINNER MARKET-SHARE

By Mark A. York (August 28, 2018)

 

 

 

 

 

 

 

Two recent Xarelto studies fail to show additional benefits when Bayer and Johnson & Johnson’s attempted to expand the patient group for their heart drug Xarelto.

The recent Xarelto blood thinner “Commander HF” study, (see  https://clinicaltrials.gov/ct2/Bayer/J&J (Commander AF Study), could not show any statistical improvements in helping heart failure patients after an acute decline in their condition, results from the so-called study showed on Monday. The primary study goal of reduction in the risk of death, heart attack and stroke was unsuccessful.

A second Bayer/J&J study known as “Mariner” also failed to produce clear evidence that Xarelto is able to reduced the rate of blood clots in certain high-risk patients after a hospital release.

Bayer earned $3.84 billion in sales of Xarelto revenues last year, primarily from stroke prevention in the elderly, with projected annual sales to rise above $5 billion in 2019 and beyond.

Bayer retains marketing rights for Xarelto outside the United States while partner J&J sells Xarelto in the U.S., with Bayer being eligible for royalties on U.S. sales of 20 to 30 percent.

Both Bayer and J&J’s Janssen R&D are facing thousands of lawsuits across the country over failure to warn and disclose the significant dangers of being prescribed Xarelto and the inability to stop the bleeding as there hasn’t been an antidote for Xarelto until 2018.

XARELTO MDL 2804 AND PHILADELPHIA COMPLEX LITIGATION DOCKET

Between the Xarelto MDL 2804 federal docket of 25,000 plus and the 1,700 in Philadelphia Court of Common Pleas there seems to be significant concern for the use of Xarelto when a comparison is made to the pre-Xarelto blood thinners i.e. Coumadin and Warfarin which required additional monitoring, are not known as a drug that can kill you.

Mass Tort Nexus Briefcase Re: XARELTO-Case-No-2349-in-Philadephia-Court-of-Common-Pleas–Complex-Litigation-(PA-State-Court)

Mass Tort Nexus Briefcase Re: XARELTO-MDL-2592-US-District-Court-ED-Louisiana

HOW XARELTO WAS APPROVED BY THE FDA

Xarelto was first approved by the FDA July 2011, representing a major advancement in blood thinning (anticoagulant) medication according to Bayer and Johnson & Johnson, developed to prevent serious conditions that sometimes arise after surgeries (such as artificial hip and knee surgeries). As an anticoagulant, it was intended to prevent pulmonary embolism (PE) and deep vein thrombosis (DVT) and strokes. Xarelto was also intended to help those patients with atrial fibrillation, a group of people more vulnerable to PE, DVT, and stroke after surgery. Eventually, the FDA expanded approval of Xarelto to treat all patients with PE, DVT and atrial fibrillation.

More than one study has shown Xarelto can cause a higher rate of internal bleeding, than other anticoagulant drugs and there is no available “antidote” for stopping internal bleeding in patients taking Xarelto. With warfarin, vitamin K has been shown to stop bleeding, but there is no vitamin K “parallel” for people taking Xarelto. For Xarelto, it can take 24 hours for a dose to get out of the body. That means that if internal bleeding starts, the patient may simply have to wait it out and hope it stops on its own.

 MAYO CLINIC XARELTO STUDY RESULTS NOT POSITIVE

In the journal Gastroenterology, a team of physicians and researchers from the Mayo Clinic studied thousands of patients who took Xarelto (rivaroxaban), Pradaxa (dabigatran), and Eliquis (apixaban). The goal was to figure out which of these three anticoagulant drugs had “the most favorable GI safety profile,” which is medical-research-speak for “which one of these drugs is least likely to hurt patients.”

This is how the study worked: The researchers studied health insurance administrative claims information on thousands of patients between October 1, 2010 and February 28, 2015. These patients had atrial fibrillation, or Afib, which is a heart arrhythmia, a quivering or irregular heartbeat. Afib can lead to serious health problems such as stroke, blood clots, heart failure and other health complications. The researchers looked at the incidents of gastrointestinal bleeding among the thousands of patients who took Xarelto or Pradaxa or Eliquis.

MAYO STUDY SHOWS NEGATIVE RESULTS

Patients who took Xarelto had a higher incidence of gastrointestinal (GI) bleeding patients who took Pradaxa or Eliquis. The statistics show that patients taking Xarelto may have a 20% greater risk of internal bleeding than with those taking Pradaxa or Eliquis, with the rates of GI bleeding increased in patients over seventy-five (75) years old. Turns out, Eliquis “had the most favorable GI safety profile among all age-groups.” While clearly showing Xarelto, unfortunately, had the “least favorable” safety profile among the three prescription anticoagulant drugs.

FDA Investigation of Xarelto Trials

The approval history for Xarelto was actually pretty controversial. FDA reviewers originally said that they recommended against approval, then there was an FDA advisory committee (independent group of key opinion leaders) and they voted in favor, so the FDA approved the drug. Their concern was with how the Phase III trials were run and whether Xarelto had really proved its efficacy. The tests compared patients on warfarin to patients on Xarelto, but the patients on the warfarin run had poor TTR. That means the patients weren’t well controlled on warfarin to begin with, which skews the data in favor of Xarelto.

During the approval process, Xarelto actually wanted a superiority label, which would say that the drug was better than warfarin and other blood thinners. Because of the concerns with the Phase III data, the FDA only gave them a non-inferior label, which says they’re essentially the same in terms of effectiveness.

One of the clinical trials that played a key role in its approval for stroke prevention in patients with atrial fibrillation is now under investigation by the FDA. This trial compared Xarelto’s performance to warfarin’s, but it used a device called INRatio to test the warfarin patients.

The INRatio device was the subject of two FDA warning letters about inaccurate readings just as the trial was starting in 2005 and 2006. In 2014, the device was recalled. The use of the INRatio device may have skewed the results with inaccurate readings, making Xarelto look better in comparison with warfarin.

The FDA’s medical experts originally recommended against improving the drug due to concerns about its efficacy. They found that Xarelto was not as effective as warfarin. However, a review board eventually approved the drug over the objections.

The FDA has issued a number of warnings about Xarelto and has required the makers of the drug to change its labeling multiple times. Specifically, the FDA warned about the risks of uncontrolled bleeding. It also added a black-box warning, its most serious kind of warning, about the increased risk of stroke when patients prematurely stop taking Xarelto and about the increased risk for swelling and damage associated with the use of epidural anesthesia while taking Xarelto.

The makers of Xarelto recently applied to the FDA to expand the approved uses of the drug to include treatment for acute coronary syndrome (ACS). For the third time, the FDA unanimously denied the expansion. Johnson & Johnson and Bayer are expected to continue to apply for approval due to the high value of that market. More than 1 million patients are hospitalized with ACS each year. That offers serious potential for growth for Xarelto, which already earns almost $1 billion in sales annually.

Johnson & Johnson also is claiming that Xarelto helps patients with peripheral artery disease (PAD) in reducing their heart attack and blood clot risks.

WHAT THE VETERANS ADMINISTRATION SAYS ON XARELTO USE

“The good news is you now have an alternative to warfarin … The bad news is you can kill a patient as easily with the new drug as you could with the old drug.”Dr. Alan Jacobson, Director of anti-coagulation services at the VA in Loma Linda, Calif.

The makers of Xarelto say it takes time for doctors to get up to speed on new types of treatments and how to best administer them outside the controls of clinical trials.

“This is a shift in medical practice,” said Dr. John Smith, senior vice president for clinical development at Boehringer. “Individual physicians have to determine what the follow-up plan will be, to use common medical-sense judgment.”

XARELTO MAKERS SAY NO FOLLW-UP CARE REQUIRED

Dr. Peter Wildgoose, a senior director of clinical development at J&J, said the company has not provided special advice on follow-up care for patients on Xarelto.

“There’s nothing more than for any other drug that people regularly take,” he said, adding that most atrial fibrillation patients probably see their doctors on a regular basis. “These drugs have been tested long term, for several years at a time, with very good outcomes.”

Johnson & Johnson officials stressed there was far less evidence in trials of brain bleeding – the most worrisome side effect of anti-coagulants – in patients taking Pradaxa and Xarelto than those taking warfarin.

WAS XARELTO EVEN NEEDED?

Even though warfarin (Coumadin) has been the standard in anticoagulant (blood thinner) drugs for more than 50 years, it lacked perfection, making way for a new generation of blood thinners, including Xarelto. In clinical studies, Xarelto was shown to be more effective than warfarin in treating patients with atrial fibrillation (AF) who are at an increased risk for stroke. And while Xarelto had less cranial hemorrhage (bleeding in the brain) incidents than warfarin, it was shown to have a similar overall number of bleeding incidences when compared to the number of bleeding events in patients taking warfarin.

Despite this finding, and – until recently – its lack of antidote (reversal agent) for serious bleeding, Xarelto rose to popularity, making up a significant portion of the billion-dollar anticoagulant drug industry in the United States. Even after an investigation into into the clinical trial ROCKET-AF study, upon which its U.S. Food and Drug Administration (FDA) approval hinged, the drug continues to be prescribed by doctors to patients with AF and as a prophylaxis for deep vein thrombosis (DVT), which can lead to pulmonary embolism (PE) after total hip and knee replacement surgeries.

But as more evidence surfaced regarding the drug risks for patients taking Xarelto, including an increased risk of wound complications following surgical procedures, severe bleeding with no easily available antidote to stop its serious consequences, as well as reports of platelet deficiencies, hepatitis and Stevens-Johnson syndrome (SJS) (a severe skin reaction), some heart doctors are becoming a bit more cautious with the blood thinner.

Xarelto and Internal Bleeding?

Janssen and parent company Johnson & Johnson market its anticoagulant drug Xarelto as a safe and more convenient choice in blood thinners compared to warfarin. But pre-market clinical studies and post-marketing reports have shown that taking Xarelto leaves many patients vulnerable to internal bleeding that can result in death for some users.

In a 2017 annual report issued by the Institute for Safe Medication Practices (ISMP), it was stated that oral anticoagulant drugs, including Xarelto (rivaroxaban), showed “unacceptably high risks,” according to two government data sources, the FAERS adverse events reports for 2016 and a new systematic study by the Centers for Disease Control and Prevention (CDC).

XARELTO ACCOUNTS FOR 75 PERCENT OF ALL AE’s IN ANTI-COAGULANTS

Of the 22,000 reports of serious injuries resulting from anticoagulant drugs, Xarelto accounted for 15,043 cases alone, the FDA said.

“According to an analysis of 2016 FDA adverse event data conducted by the ISMP, anticoagulant (blood thinner) drugs accounted for nearly 22,000 reports of serious injuries in the United States, led by Xarelto, which accounted for 15,043 cases alone. These numbers also included 3,018 reported deaths, with most injuries being the result of hemorrhages, making bleeding one of the most adverse events.”

Gastrointestinal hemorrhages made up the MOST INJURIES, followed by cerebral hemorrhages. From early testing, hemorrhage has always been an apparent increased risk associated with lowering the risk of strokes from blood clots.

In late 2016, the CDC released a separate study that found that “anticoagulant drugs accounted for more emergency department visits for outpatient adverse effects than any other class of drugs currently in therapeutic use, including opioids (non-abuse visits), antibiotics and diabetes drugs.” Most of these adverse events were severe, with nearly 50 percent requiring a hospital stay. The ISMP estimated in its QuarterWatch report that just over 6 percent of patients using anticoagulants for one year will need to visit the emergency room, with about half of those patients requiring hospitalization. That is a major number of injuries that can be attributed to a drug that is advertised as life saving and designed to prevent injuries.

Overall, the CDC found in its systematic study that the FDA’s FAERS voluntary reporting underestimates anticoagulant drug-related injuries. The CDC discovered that approximately 228,600 emergency department visits occur each year due to the use of blood thinner drugs, including Xarelto, which is 10 times more than the FAERS total number of voluntary reports.

The Symptoms of Internal Bleeding

At its onset, unless it’s a severe hemorrhage, internal bleeding may not cause any symptoms apparent to the patient taking Xarelto. However, dependent on where the bleed is located in the body, the patient will soon begin exhibiting signs and symptoms that will be their indication to seek immediate medical attention. Patients who are in poor health or are over the age of 64 and the targeted audience seem more likely to suffer serious, potentially life-threatening bleeding complications.

The end result of Bayer and J&J’s attempts to secure the blood thinner market may continue unabated until the more than 25,000 lawsuits over the injuries and deaths that are affiliated with taking Xarelto will force both companies to come to either the settlement table or begin trying the Xarelto MDL 2592 lawsuits being remanded back to original courts for trials and blocks of 1200 cases at a time. Xarelto MDL Judge Eldon Fallon, USDC Eastern District of Louisiana has already started the remand process for 23,000 cases pending in his federal court, due to the lack of progress in settlements and cooperation by Bayer and Johnson & Johnson.

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