PARIS—Servier, the pharmaceutical company at the heart of a massive medical scandal in France, suffered several fresh blows to its credibility this week. Yesterday, a newspaper revealed that the company has come under fire from Europe's medicine watchdog for the way it studied the side effects of its drugs after they reached the market. Meanwhile, leaked court testimony by two former company scientists suggests that Servier deleted unfavorable information from the files with which it sought regulatory approval for Mediator, its diabetes drug, in the 1970s.
Mediator—Servier's brand name for a drug called benfluorex—was banned in November 2009 after 33 years on the French market. Although marketed as a diabetes drug, doctors widely prescribed it for people who wanted to lose weight as well. Mediator has been shown to cause serious heart valve problems, however, and it's now estimated to have caused up to 2000 deaths. A French court is investigating the case, and the French government has announced that it will tighten regulatory oversight of drugs in response.
Yesterday, French newspaper Libération reported that the European Medicines Agency (EMA) in London has set its sights on Servier as well—initially for problems around strontium ranelate, an osteoporosis drug marketed by Servier in France under the name Protelos. An estimated 390,000 French women in France have taken the drug during the last 4 years.
Dominique Maraninchi, head of the French regulatory agency AFSSAPS, confirmed EMA's worries in a telephone interview with ScienceInsider. In November 2007, EMA's Pharmacovigilance Working Party issued a warning that Protelos could cause severe and potentially fatal skin rashes known as Drug Reaction with Eosinophilia and Systemic Symptoms, and ordered Servier to correct "flaws" in its system to keep track of such adverse events, Maraninchi says.
EMA asked AFSSAPS to carry out an inspection in December 2009 to ensure Servier had followed up. That inspection revealed other "critical and major findings," this time with Servier's manufacturing process, and raised concerns over all of the company's drugs, says Maraninchi. As a result, Servier was ordered to submit information on all of its medicines to EMA, whether authorized for marketing by EMA itself or by national agencies.
EMA eventually concluded that the benefit-risk balance remained positive for Servier's drugs, but it instructed the company to provide extra product information for some of them, an EMA spokesperson says. AFSSAPS carried out a second inspection in July of this year and will present its findings by the end of this month.
On Tuesday, reports in the newspapers Le Figaro and Libération also cast doubts on Servier's integrity when it applied for regulatory approval for Mediator in 1973. The papers quoted from the court testimony of retired neurosurgeon Jean Charpentier, now 81, who prepared the regulatory file at the time. Charpentier, who started working for Servier in 1968, reportedly told the judges that clinical trials had shown Mediator to be a powerful appetite-suppressant, but that this was downplayed in his report to get Mediator approved as an antidiabetic drug. (Diabetes was "an infinitely more profitable choice" than weight loss for pharmaceutical companies, said Charpentier.)
The report also didn't mention that Mediator is an amphetamine derivative, Charpentier said in his testimony. "The word amphetamine was to be avoided," he said.
Jacques Duhault, 78, a pharmacist who headed the company's diabetes and obesity lab in the 1960s, told the judges he regretted that Servier didn't pull Mediator as a precautionary measure in 1999, Libération reported. His studies described the drug as a "powerful appetite suppressant." In January 1969, he said that the drug, then known by its code name S992, "causes almost total anorexia from the first day."
Servier has dismissed all of the allegations. In press statements, the company has condemned the breach of judicial secrecy over the Mediator testimonies, reaffirmed that it had "deceived neither the health authorities nor patients," and denied that any of Charpentier's studies had been tampered with.