Drug Injury Watch

Xolair Is Associated With Higher Than Expected Reporting Of Arterial Thrombotic Events Such As Strokes And Cardiovascular Deaths

While European Drug Regulators Have Been Concerned About This Aspect Of Xolair Safety, FDA Has No Warning About Arteriothrombotic Risks Of Xolair

(Posted by Tom Lamb at DrugInjuryWatch.com)

In September 2014 the FDA issued an update about its safety review of the Genentech asthma medication Xolair (omalizumab), which we reported about in this earlier post, "Xolair Asthma Drug Associated With Higher Rate Of Heart Attacks, Pulmonary Hypertension, Blood Clots Causing PEs And/Or DVTs, And Brain Blood Vessel Problems".

From the Data Summary of that September 26, 2014 FDA Drug Safety Communication:

The manufacturer of Xolair, Genentech, initiated the postmarketing commitment study titled An Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-Term Safety in Patients with Moderate to Severe Asthma (EXCELS) in June 2004 to assess the long-term safety of Xolair

A higher incidence rate per 1,000 patient years of overall cardiovascular and cerebrovascular serious adverse events was observed in Xolair-treated patients compared to non-Xolair-treated patients, as well as for myocardial infarction, unstable angina, transient ischemic attack, pulmonary embolism/venous thrombosis, and pulmonary hypertension. No increases in the rates of ischemic stroke or cardiovascular death were observed in patients treated with Xolair compared to non-Xolair-treated patients.

In this post we consider a medical journal article which takes issue with that last sentence as it reached the opposite conclusion; specifically, Xolair is associated with an increased risk of arterial thrombotic events, predominantly cardiovascular deaths and strokes.

The subject article is "Assessing the association between omalizumab and arteriothrombotic events through spontaneous adverse event reporting", initially published online by the Journal of Asthma and Allergy back in May 2012.

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This 2012 journal article came from two medical researchers at the Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, who wanted to analyze the association between Xolair and arterial thrombotic events.  In the Introduction part of their article they noted:

In February 2011, the UK Medicines and Healthcare Products Regulatory Agency advised prescribers to be vigilant about the possible occurrence of arterial thrombotic events in patients exposed to [Xolair (omalizumab)].... These recommendations were based on interim analyses of randomized clinical trials and an unpublished cohort study, ie, EXCELS (Evaluating Clinical Effectiveness and Long- Term Safety in patients with Moderate-to-Severe Asthma). These analyses yielded a statistically insignificant increase in the risk of arterial thrombotic events in groups exposed to [Xolair (omalizumab)] compared with their unexposed control counterparts.... The FDA reviewed the reported adverse events for [Xolair (omalizumab)] in July 2009, and concluded with a warning to prescribers and patients about hypersensitivity reactions, with no reference to any arteriothrombotic risks. This study assessed the safety profile of [Xolair (omalizumab)] with respect to arterial thrombotic events recorded in the FDA Adverse Event Reporting System (AERS) database [from the period 1/1/2004 to 1/1/2011].

According to these University of Florida researchers, their study is the first pharmacovigilance analysis to detect from a spontaneous event reporting database such as the FDA AERS a strong safety signal for Xolair as regards cardiovascular death and stroke events.

From the Results section, in particular "Reporting odds ratio data mining algorithm results":

Cardiovascular death and stroke ranked first on the arterial thrombotic events list in detection of statistically significant safety signals (reporting odds ratio 3.14, 95% CI 2.14–4.56; reporting odds ratio 3.14, 95% CI 2.41–4.05, respectively). Although the reporting odds ratio values for ischemic heart disease, myocardial infarction, and thrombosis risk exceeded 2.0, the lower limit of the 95% CI failed to reach that threshold, making the estimates less significant as safety signals (reporting odds ratio 2.63, 95% CI 1.92–3.63; reporting odds ratio 2.55, 95% CI 1.98–3.29; reporting odds ratio 2.19, 95% CI 1.18–4.01, respectively).

Numerous times throughout their article the authors acknowledge the limitations of their research methods and state that epidemiological studies are necessary to further explore the apparent association of Xolair with cardiovascular deaths, strokes, and other arterial thrombotic adverse events.

Their Xolair analytical study, however, does serve to expand one's range of concern about the drug safety profile for Xolair, which has been available in the US since June 2003.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Case review done by attorney Tom Lamb) 

Eliquis Antidote Will Come Too Late For People Who Suffered Serious Bleeding Events, Some Which Caused The Deaths Of Patients

Advertisements As Well As Prescribing Information / Drug Label Seem To Downplay The Fact That There Is No Reversal Agent For Eliquis, Yet

(Posted by Tom Lamb at DrugInjuryWatch.com)

In print advertisements for their relatively new blood thinner medicine Eliquis, Bristol-Myers Squibb and Pfizer state in the Important Safety Information section ("August 2014" version):

ELIQUIS can cause bleeding, which can be serious, and rarely may lead to death.

But at the very start of these print ads, in larger print, is this point -- #2 of "3 GOOD REASONS":

ELIQUIS has less major bleeding than warfarin.

If one delves further into the Eliquis advertisements you may see in popular magazines, you will find this:

While taking ELIQUIS... it may take longer than usual for any bleeding to stop.

What you will not see, however, is any statement to the effect that there is no reversal agent to stop a serious bleeding event that may happen while a patient is on Eliquis. That is, Bristol-Myers Squibb and Pfizer do not state in these advertisements that there is no FDA-approved antidote for Eliquis as regards its blood-thinner effect at this time.

Put simply, there seems to be a failure to warn patients that the risk of death is higher once one starts to bleed due to a traumatic event, for example.

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To be clear, the Prescribing Information for Eliquis from Bristol-Myers Squibb and Pfizer ("Rev August 2014" version) -- which is usually only seen by medical doctors and, perhaps, other health care providers -- says this in the Warnings And Precautions section:

There is no established way to reverse the anticoagulant effect of [Eliquis apxiaban)], which can be expected to persist for at least 24 hours after the last dose, i.e., for about two drug half-lives. A specific antidote for ELIQUIS is not available.

Instead, the drug company could perhaps tell all of us that the risk of death is higher once patients using Eliquis start to bleed due to a traumatic incident, or an unrecognized internal bleeding event, such as a gastrointestinal (GI) bleed.

Accordingly, it was good to see the recent news reports and a drug company press release that there are some apparent developments in getting an Eliquis antidote approved by the FDA and, ultimately, available for us with patients who need it.

Here is one of the recent news reports, "ANNEXA-A: Antidote reversed anticoagulant effect of apixaban", published on December 15, 2014:

Andexanet alfa safely and effectively reversed the anticoagulant effects of [Eliquis (apixaban)] among older patients, according to data presented at the American Heart Association Scientific Sessions [in Chicago].

And as regards the Bristol-Myers Squibb and Pfizer press release, "Anticoagulant Effect of Eliquis (apixaban) Reversed by Two Separate 4-Factor Prothrombin Complex Concentrates in Healthy Subjects".

But this movement towards a possible Eliquis antidote is too late in some of the Eliquis drug injury cases which we are currently investigating, including these:

• 79 year old woman - Internal Bleeding and Rectal Bleeding; hospitalized 6 days
• 52 year old man – Gastrointestinal (GI) Bleed; hospitalized 8 days
• 76 year old woman - Hemorrhagic Stroke / Irreversible Bleeding Event; Death
• 79 year old man – Serious Internal Bleeding; Death

While we hope there will be an Eliquis antidote available soon for those patients who may need it, unfortunately it comes too late for some who did -- but it was not available, with tragic consequences.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Case review done by attorney Tom Lamb) 

December 2014 YAZ / Yasmin Litigation Update: Still Over 2000 DVT And/Or PE Cases Not Settled According To Bayer's Most Recent Financial Report

And New Blood Clot Side Effect Lawsuits, Including Some Involving The Lesser-Known Safyral And Beyaz DRSP Pills, Are Still Being Filed Against Bayer

(Posted by Tom Lamb at DrugInjuryWatch.com)

Bayer's latest update on the ongoing litigation concerning its drospirenone (DRSP) birth control pills -- Yasmin, YAZ, Safyral, and Beyaz -- as set forth in its Stockholders' Newsletter Financial Report as of September 30, 2014, published on October 30, 2014, is as follows:

Yasmin™ / YAZ™: As of October 13, 2014, the number of claimants in the pending lawsuits and claims in the United States totaled about 4,000 (excluding claims already settled). Claimants allege that they have suffered personal injuries, some of them fatal, from the use of Bayer’s drospirenone-containing oral contraceptive products such as Yasmin™ and / or YAZ™ or from the use of Ocella™ and / or Gianvi™, generic versions of Yasmin™ and YAZ™, respectively, marketed by Barr Laboratories, Inc. in the United States.

As of October 13, 2014, Bayer had reached agreements, without admission of liability, to settle the claims of approximately 9,200 claimants in the U.S. for a total amount of about US$1.8 billion. Bayer has only been settling claims in the U.S. for venous clot injuries (deep vein thrombosis or pulmonary embolism) after a case-specific analysis of medical records on a rolling basis. Such injuries are alleged by about 2,100 of the pending unsettled claimants. Bayer will continue to consider the option of settling such individual lawsuits in the U.S. on a case-by-case basis.

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This information can be compared to what we found in Bayer's prior corporate financial report, as discussed in this post, "Summer 2014 Update YAZ / Yasmin / Ocella / Gianvi Litigation: Bayer Reports On Total Settlements And Number Of Pending Claims":

• Settlements with about 8,900 claimants for total of $1.8 billion;
• The number of pending claims with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) -- the "venous clot injuries" -- is approximately 2400; and,
• There are an estimated 2,600 claims with other alleged drospirenone (DRSP) related injuries, such as arterial clots.

To put all of this into context, the YAZ / Yasmin litigation began back in mid-2009 when the first lawsuits against Bayer were filed.  In January 2012 Bayer decided to begin to attempt to negotiate settlements for YAZ / Yasmin / Ocella / Gianvi blood clot lawsuits, e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE), on a case-by-case basis.  And new lawsuits, including some cases involving Safyral and Beyaz, are still being filed against Bayer to date.

We will continue to monitor this Bayer birth control pills litigation and periodically report developments here, as we have over the past few several years.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Case review done by attorney Tom Lamb)

December 2014 Fosamax - Femur Fracture Litigation Update: In The Fosamax Federal Court MDL There Are Dismissals, Appeals, And Court-Ordered Mediations

Judge Pisano's Rulings About Merck's Pre-September 2010 Fosamax Label And Its Subsequent Revised Fosamax Label Are Being Challenged By The Plaintiffs

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

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UPDATE: On March 22, 2017 the Third Circuit Court of Appeals reversed the dismissal by U.S. District Court Joel Pisano of all the pending federal court Fosamax - femur fracture cases nationwide on federal preemption grounds. The Third Circuit significantly held that the ultimate question of whether the FDA would have rejected a Fosamax label change by Merck for the increased risk of femur fractures is a question of fact for the jury, rather than for the court, to decide.

(3/23/17)

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We are drawing from this Merck corporate SEC filing, "Form 10-Q, For the quarterly period ended September 30, 2014" (at pp. 20-21 of PDF file), for this update on the Fosamax - femur fracture lawsuits.

While most of these drug injury lawsuits filed against Merck are pending in the New Jersey state court system -- as of September 30, 2014, approximately 2,920 cases, according to Merck -- we are going to focus on what is going on currently in the federal court Fosamax MDL for femur fracture cases.

Federal District Court Judge Joel Pisano is presiding over this Fosamax MDL.  And from the most recent Merck Form 10-Q SEC filing we get these facts about what has been going on in that litigation:

[O]n March 26, 2014, Judge Pisano issued an opinion finding that all claims of the approximately 650 plaintiffs who allegedly suffered injuries prior to September 14, 2010 were preempted and ordered that those cases be dismissed. The majority of those plaintiffs are appealing that ruling to the U.S. Court of Appeals for the Third Circuit. Furthermore, on June 17, 2014, Judge Pisano granted Merck summary judgment in the Gaynor v. Merck case and found that Merck’s updates in January 2011 to the Fosamax label regarding atypical femur fractures were adequate as a matter of law and that Merck adequately communicated those changes. The plaintiffs in Gaynor have appealed Judge Pisano’s decision to the Third Circuit. In August 2014, Merck filed a motion requesting that Judge Pisano enter a further order requiring all remaining plaintiffs in the Fosamax Femur Fracture MDL to show cause why their cases should not be dismissed based on the court’s preemption decision and its ruling in the Gaynor case that the 2011 Merck label is adequate as a matter of law. Plaintiffs have opposed that motion and asked the court to stay the remaining cases in the Fosamax Femur Fracture MDL until the Third Circuit rules on their appeal of Judge Pisano’s preemption decision. In September 2014, Judge Pisano also ordered the parties to participate in a mediation process.

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One other thing to report is the possibility of a Fosamax - femur fracture trial in the first part of 2015 out in Orange County, California. The presiding judge for this California consolidation -- as of September 30, 2014, approximately 520 cases, according to Merck -- is Judge Thierry Colaw.  From the above-referenced Merck SEC filing:

In March 2014, the court directed that a group of 10 discovery pool cases be reviewed through fact discovery and subsequently scheduled the Galper v. Merck case as the first trial for February 2015. Two additional trials are scheduled for May and July 2015.

For background, here are the last two updates on this litigation:

• End Of Summer 2014 Update: Fosamax - Femur Fracture Lawsuits In The New Jersey Consolidation / Multicounty Litigation
• June 2014 Fosamax - Femur Fracture Litigation Update: Thousands Of Cases Pending, But No Trial Dates Currently Scheduled In Federal Court MDL Nor New Jersey Multicounty Litigation

We will continue to monitor the Fosamax - femur fracture cases in the federal court MDL as well as New Jersey and California litigations for significant developments, which will be reported here.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Case review done by attorney Tom Lamb)