On the eve of an FDA advisory committee meeting being held to review the risks and benefits of various birth control meds - notably the Yaz and Yasmin pills sold by Bayer - newly unsealed documents in the sprawling litigation involving the Bayer drugs show that former FDA commish David Kessler offered a scathing expert opinion that the drugmaker wrongfully withheld safety info from regulators.
His 196-page report was one of several such expert opinions that were released by a federal court in Illinois, where some thousands of lawsuits are pending over alleged injuries and deaths relating to Yaz and Yasmin, as well as generics. Meanwhile, on Thursday, the FDA will convene two committees to examine the risk of blood clots linked to birth control pills containing a hormone called drospirenone (here are the briefing materials). However, the FDA may not accept the documents for the hearing, because a submission deadline passed. Plaintiffs lawyers had been fighting in court to unseal the documents in time for the hearing (see this).
The lawsuits allege Yaz and Yasmin have risks beyond those of traditional birth control pills and Bayer too aggressively promoted the pills without disclosing those higher risks. Earlier this year, a pair of studies found that women taking birth control pills containing drospirenone are more likely to develop blood clots than those who take an older oral contraceptive (see this and this).
In his report, Kessler cites a host of actions that Bayer failed to take to mitigate safety risks associated with its pills. Overall, he wrote that "Bayer violated its duties under FDA regulations and state law by selectively presenting data as to thromboembolic events, which did not adequately inform FDA, doctors or consumers of the thromboembolic risks, from pre-marketing to the present."
He supports the contention in the lawsuits that Bayer "engaged in extensive off-label promotion of Yasmin and Yas for unapproved uses, in violation of FDA regulations, to increase sales. That off-label promotion increased the risk of thromboembolic events in patients in violation of state law duties." For instance, Bayer was warned by the FDA in 2008 that TV ads were misleading and did not disclose added risk info.
More specifically, he wrote that serious adverse events observed in a clinical study should have been reported to the FDA prior to approval of Yasmin, but that Bayer chose not to do so. The FDA requested a proposed change to the warning label to indicate an increased risk, but Bayer did not provide the FDA with any proposed changes.
He also wrote that Bayer knew, based on its own analysis, that Yasmin had an increase in the US reporting rate of various side effects, notably blood clots, compared to other contraceptives, but the drugmaker omitted this info from its analysis that it presented to the FDA. "In my opinion, had I, or a medical review officer, known these facts prior to approval, further investigation would be warranted before a decision on Yasmin’s NDA could be made. These facts would impact the Agency’s risk-benefit equation about the drug and whether it could be approved," he wrote.
His report is replete with various instances in which, in his opinion, Bayer bobbed and weaved in an attempt to avoid FDA actions. Based on adverse event reports in 2003, including six deaths, the FDA told the drugmaker that a labeling change for venous thromboembolisms, or blood clots, was being considered. But Kessler determined that Bayer omitted data from a post-marketing surveillance study, or white paper, that was submitted to the FDA in 2004, and later failed to disclose blood clot risk into to the FDA, doctors and the public in 2008 and 2010.
For instance, in a draft of the August 2004 white paper, Bayer employees wrote: “Compared to the three other (oral contraceptives), Yasmin has a several fold increase in the reporting rates for (deep vein thrombosis), (pulmonary embolism) and confirmed VTEs...When considering only serious AEs, the reporting rate for Yasmin was 10 fold higher than that with the other products which were very similar in magnitude." Bayer employees argued in a revised draft that "spontaneous reporting data do signal a difference in the VTE rates for Yasmin and other OC users."
In rebuking Bayer, Kessler wrote that "analysis of spontaneous reporting data has limitations including, but not limited to, the voluntary nature of the reporting; effects of media attention; different time periods of introduction; different reporting patterns across sponsors; and different perceptions, characteristics and prescribing patterns of products. Even with its limitations, analysis of spontaneous reporting data is an important, recognized, and vitally used tool by the FDA and the pharmaceutical industry for detecting safety signals" (you can read the complete report here and pages 27 to 33, specifically).
In all, he suggested that Bayer "viewed the regulatory environment" regarding the safety of the pills as a "threat...In my opinion, Bayer employed a strategy to avoid strengthening Yasmin’s VTE warning and selectively presented data to the FDA." And he concluded that "Bayer’s economic success was achieved, in part, by marketing and promoting Yasmin And Yas for off-label indications in violation of the law and its duty of care" (you can read the complete report here).
Here is one example. A November 2004 Bayer document that Kessler cites is called “Public Relations Recommendations for Yaz & Yasmin” and listed “Book interviews for Yasmin spokesperson - high-profile GYN (Dr. Judith Reichman).” As Kessler notes, Bayer had a deal with Reichman to promote Bayer products.
Specifically, the drugmaker paid her $450,000 for, among other things, to be the exclusive sponsor of her book tour and had rights to review her book, “Slow the Clock Down,” prior to its publication. However, Kessler concluded that "Dr. Reichman’s book advocated the use of Yasmin for indications beyond the FDA-approved label" and that, "by paying for the promotional activities associated with Dr. Reichman’s book, Bayer was illegally promoting Yasmin for off-label uses in violation of the Federal Food Drug and Cosmetic Act" (see pages 84 through 88 of his report).
Again, Kessler wrote this as a paid expert; he was no longer FDA commish at the time he submitted the report, which was first reported by Bloomberg News, to the plaintiff lawyers in July. But of course, the lawyers hope that his former perch will carry substantial weight during the upcoming trials, which are scheduled to begin next month in federal court. A Bayer spokeswoman, meanwhile, wrote us to say that the drugmaker has "nothing further to add as these are matters of litigation. We expect them to be addressed further at trial."