June 25, 2018
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Bayer may have marketed birth-control pill for risky uses

By Jef Feeley and Margaret Cronin Fisk, Bloomberg News

Units of Bayer, Germany’s largest drugmaker, may have sought to market the Yasmin family of birth-control pills for unapproved uses and mislead women about the health risks the drug posed, according to company e-mails.

Bayer unit officials discussed promoting the contraceptive known as Yaz, a spinoff of Yasmin, for treatment of all types of premenstrual syndrome, according to company files provided to lawyers for women suing Bayer. U.S. regulators approved Yaz only for the most severe form of PMS. Salespeople for Bayer unit Berlex Laboratories Inc., acquired in the 2006 purchase of Schering, received an e-mail that year from a company official citing a Woman’s Day magazine article about Yaz.

“This article is a nice way of using YAZ for PMS treatment instead of just focusing on the specific” class of women battling premenstrual dysphoric disorder, the most severe form of PMS, wrote Matt Sample, a Berlex sales consultant, according to a copy of the e-mail.

The message and other internal company files were disclosed as part of litigation claiming the drug caused blood clots, heart attacks and strokes. Bayer faces more than 10,000 lawsuits over injuries allegedly caused by the contraceptives. Lawyers suing the drugmaker cited Food and Drug Administration reports of at least 50 deaths tied to the pills from 2004 to 2008.

“Bayer’s oral contraceptives have been and continue to be extensively studied worldwide and are safe and effective when used as directed and according to product labeling,” said Rose Talarico, a U.S.-based spokeswoman for the company, in an e-mail. She declined further comment on the litigation.

Bayer’s contraceptives generated $1.58 billion in sales last year, making them the company’s biggest-selling drugs after Betaseron, a multiple sclerosis medication. The contraceptives, which contain the hormone drospirenone, have been the focus of regulators who question their safety.

Last month, the FDA warned that women taking the pills were 74 percent more likely to suffer blood clots than women on other low-estrogen contraceptives. The FDA examined data on 835,826 women who took pills containing the hormone, including Bayer’s Yasmin line of birth-control pills, according to the FDA report. The agency has set a Dec. 8 hearing to discuss the findings.

Besides the off-label marketing allegations, attorneys for women suing Bayer alleged internal company files show Berlex and Schering officials withheld some information from patients, doctors and regulators about the drug’s risk for blood-clots. The lawyers also claim in court filings that company officials wrongfully touted Yasmin and Yaz to be just as safe as rival birth-control pills.

The drugmaker and its units “sacrificed women’s health in its rush for profit and they continue to do so every day,” said Paul Pennock, a New York-based lawyer representing women suing over the contraceptives.

In January, Bayer is scheduled to face the first trials of lawsuits in which Yaz and Yasmin are alleged to have caused blood clots, which can lead to heart attacks and strokes. The trials are to take place in Illinois and Pennsylvania.

Bayer turned over Sample’s e-mail and other documents obtained by Bloomberg News to the plaintiffs’ lawyers as part of discovery, or the pre-trial exchange of evidence and information, in the consolidated Yaz cases.

The lawyers contend Sample’s e-mail about the Women’s Day article amounts to an effort to have Yaz promoted for a use not approved by the FDA. Under U.S. law, a doctor can prescribe a medicine for any condition, as long as it’s licensed by the FDA and proven safe and effective.

Drug companies, however, aren’t allowed to promote a drug for uses other than those approved by the regulator.

In the e-mail, Sample encourages Berlex’s sales representatives to use the article to ask doctors “what percentage of your patient population suffers from” symptoms common to PMS, versus the more severe form of the disorder, and to seek information on “what they think the impact of Yaz will be.”

The women’s lawyers also rely on a May 2002 e-mail from Kimberly Schillace, then a Berlex executive, about a contract with Dr. Judith Reichman, a Los Angeles-based gynecologist who writes a blog about women’s health issues. A copy of the e-mail was included in the litigation discovery files.

The attorneys contend the e-mail supports their arguments that the drugmaker sought to market the Yasmin line of contraceptives for unapproved uses.

In the e-mail, Schillace noted that she spoke with Reichman, who appeared regularly on NBC’s “Today” show as a contributor on women’s health.

“She definitely will mention the off-label benefits of our products,” Schillace said, according to the copy of the e-mail.

“Attached please find the contract,” the e-mail states. The message doesn’t contain details of the agreement.

Sample couldn’t be immediately reached for comment. It is unclear whether he is employed by Bayer, which didn’t respond to requests for comment on his status. Schillace, referred to in a 2006 Schering press release as Kimberly Schillace Wix, declined to comment, saying only she is no longer with Bayer.

Reichman noted in a November 2003 MSNBC.com article that some studies showed Berlex’s Yasmin “may be helpful in diminishing PMS-like symptoms.” In her 2005 book, “Slow Your Clock Down,” Reichman wrote that Yasmin may help women with PMS-related symptoms such as “fluid accumulation and bloat,” or with depression.

The FDA approved Yasmin only as a contraceptive. The regulator hasn’t cleared it as a treatment for any form of PMS or other ailments, according to the agency’s website. Reichman didn’t return calls seeking comment on the e-mail.

The FDA said Bayer made misleading claims about Yaz in television advertising, which prompted the drugmaker to spend $20 million on corrective spots. U.S. regulators said in 2008 that Bayer overstated the pill’s effectiveness and minimized “serious risks associated” with it in two 60-second television ads. The regulator said the spots misled viewers about approved uses for the drug.

FDA officials ordered the company to pull the ads. The following year, Bayer agreed to run new ads stating Yaz hadn’t been approved as a treatment for all forms of PMS or acne as part of a settlement of a claims brought by 27 U.S. state attorneys general.

Nearly 12 million women in the United States and more than 100 million women worldwide use oral contraceptives, Scott Monroe, an FDA official, said last year.

Bayer bought Schering, then a rival German drugmaker, and its New Jersey-based Berlex unit for $21.8 billion to acquire the Yasmin line of contraceptives and Bataseron. North American revenue from the birth-control pills has fallen as the pharmaceutical company, faces competition from generics made by Teva Pharmaceutical Industries.

The first trial over the pills is to start Jan. 9 in federal court in East St. Louis, Ill. The plaintiff, Kerry Sims of Belleview, Ill., contends she developed a blood clot and a lung disorder after taking Bayer’s medicine in July 2008.

Bayer “denies that any of the plaintiff’s alleged injuries were caused by Yas and/or Yasmin,” the company said in a Nov. 16 filing in the suit. “The labeling for Yaz and Yasmin provides appropriate warnings regarding the risks.”

“All birth control pills approved for use in the U.S. are associated with reports of adverse events, including death,” lawyers for the company said.

About 10,400 suits have been filed over injuries allegedly caused by the contraceptives, Bayer officials said last month in a filing with the Securities and Exchange Commission. Some of the cases have been consolidated before U.S. District Judge David Herndon in East St. Louis.

The FDA scheduled its December hearing on drospirenone-laden contraceptives, such as the Yasmin line, because of “the conflicting nature of the findings from six published studies evaluating this risk,” the agency said in September.

The FDA advisory committee will discuss “the benefits and risks” of contraceptives such as Yasmin and Yaz “in light of the emerging safety concern that the risk of venous thromboembolism (blood clots that can break loose and move within the circulatory system) associated with use of these products may be higher compared to oral contraceptives that contain the progestin, levonorgestrel,” Morgan Liscinsky, an FDA spokeswoman, said in a Nov. 18 e-mailed statement.

Plaintiffs’ lawyers said company-sponsored studies downplayed potential side effects. A Schering-sponsored study of 58,684 women using contraceptives such as the Yasmin line found no increased risk of clots.

The lead author of the European Active Surveillance Study was Juergen Dinger, then director of the Center for Epidemiology and Health Research in Berlin. Dinger previously was a Schering vice president overseeing drugs used in gynecology and played a role in the development of the Yasmin contraceptives, according to the documents provided by plaintiffs’ lawyers.

Dinger’s tenure at Schering and his involvement with the Yasmin birth-control pills weren’t disclosed in the study when the final results were published in the medical journal Contraception in 2007.

Plaintiffs’ lawyers alleged that the EURAS study was structured to minimize the number of clots linked to the contraceptives. The study results helped support sales of Yasmin and Yaz, the women’s attorneys claimed.

Maureen Cronin, a Schering executive, said in a 2005 e-mail that she met with Dinger and “reached agreement on the future reporting on EURAS” study results. The e-mail was included as an exhibit in an Oct. 27 request that the court unseal additional documents.

“One major reason for providing only tables and a synopsis is that we do not want to imply that we have a VTE problem but emphasize the fact that the study results indicate that Yasmin’s VTE/ATE is comparable to other” contraceptives, Cronin wrote, according to a copy of the e-mail. VTE refers to venous thomboembolisms, while ATE refers to clots in patient arteries.

“The document has been taken out of context,” Dinger said Nov. 18 in an e-mail. Other e-mails to which he doesn’t have access would support him, he said.

Cronin didn’t respond to a call or e-mail seeking comment about her work on the Yasmin line. She left Bayer in 2010 to become the global head of medical affairs for Vifor Pharma, a Swiss drugmaker, according to a copy of her resume posted on the Internet. A call to her there wasn’t returned.

“Bayer has sponsored several independently-conducted, large-scale, prospective, observational safety studies on the use of combined oral contraceptives,” Talarico, the U.S. spokeswoman for the drugmaker, said in her statement. “The EURAS study was designed with input and approval from the European regulatory authorities.”

“Bayer affirms that the benefit-risk profile of its oral contraceptives, based on an established body of well-grounded data, shows the risk of venous thromboembolism (VTE) is comparable to the other combined oral contraceptives studied,” she said.

The company’s assessment “is supported by consistent clinical findings over a 15-year period and up to 10 years of post-marketing study results,” Talarico said.

Pennock, the plaintiffs’ lawyer, claimed Dinger’s involvement casts doubt on the legitimacy of the science Bayer relies on to show its birth-control pills are safe.

“Schering bought and paid for allegedly independent, favorable science that was neither independent nor correct,” Pennock said in an interview. “Bayer continues to foist the myth that these drugs are not more dangerous upon millions of unsuspecting patients and doctors.”

Pennock and other plaintiffs’ attorneys asked Herndon to unseal Bayer’s files about the design and handling of the EURAS study. The lawyers said they wanted to present the materials to the FDA panel reviewing Yaz next month.

Herndon rejected that request Nov. 10, finding Bayer had a right to keep the materials related to the EURAS study confidential.

With assistance from Allison Connolly and Richard Weiss in Frankfurt, David Voreacos in Newark, NJ., Catherine Larkin in Washington and Naomi Kresge in Berlin. Jef Feeley reported from Wilmington, Del., and Margaret Cronin Fisk from Detroit.

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