September 17, 2015
By Mark Terry, BioSpace.com Breaking News Staff
A memo published by the U.S. Food and Drug Administration (FDA) regarding Sprout Pharmaceuticals’ female libido drug, Addyi (flibanserin), shows details about regulators’ concerns over the drug.
On Aug. 18, 2015, Raleigh, N.C.-based Sprout Pharmaceuticals announced that Addyi had been approved for the treatment of low sex drive in women, or what is technically called generalized hypoactive sexual desire disorder (HSDD). The drug comes with controversy, not just because it addresses a sometimes taboo subject in American culture, women’s libido, but because it has been repeatedly turned down by the FDA.
Addyi was originally developed by Boehringer Ingelheim and acquired in 2011 by Sprout. In 2010, while Boehringer was trying to develop it, the drug received a Complete Response Letter from the FDA, which basically states that “a new or generic drug will not be approved in its present form.”
Sprout resubmitted the New Drug Application (NDA) in February 2013 with additional trial data. Again, it was rejected by the FDA. The company then included data from a Phase I pharmacokinetic study and a Phase I driving study in February 2014. On June 4, 2015, an FDA panel voted 18 to 6 to recommend approval, which the FDA did on Aug. 18.
The drug will come with a Boxed Warning because of serious side effects and the need for a strict monitoring program. Addyi can cause severe low blood pressure, which can lead to fainting. This side effect is exacerbated when taken with alcohol and other drugs. It will only be prescribed by pharmacies that are certified by Sprout and will require training on counseling patients on the risks and side effects. The alcohol side effect is particularly alarming in that the drug is taken once a day, every day, and about 50 percent of people in the U.S. drink alcohol.
The memo indicates that at least three of the reviewers with the FDA recommended rejecting the drug. The memo states that those concerned suggested that “the marginal clinical benefits do not outweigh the serious risks.” Another point brought up is that one reviewer wanted more study on the Addyi-alcohol interaction in women, because most of the clinical trials focused on the alcohl interaction were conducted on men. The memo also indicates that the drug only helped about 10 percent more patients than a placebo.
The primary arguments for approval of the drug, as summarized by Hylton Joffe, director of the FDA’s Division of Bone, Reproductive and Urologic Products, was that there were no other similar drugs for women, and that physicians and pharmacists prescribing the drug are required to take an online training course. Patients are also required to sign a form citing that they are aware of the risks.
The concern about the study’s coverage of the alcohol interaction and gender appears legitimate. Apparently Sprout examined the interaction between the drug and alcohol in 23 men and two women. Given that the drug is to be prescribed solely to women, this would seem to be a legitimate concern and worrying oversight. The drug was, overall, studied in about 3,000 generally healthy premenopausal women.
“This approach is not unreasonable but, in my view,” Joffe wrote in the memo, “is not required because flibanserin is being approved, assuming that the alcohol interaction in women is at least as severe as the alcohol interaction in men. We will continue to assess the risk-mitigation approaches as more data become available.”
The FDA approved the drug with the idea that there will be three additional post-market studies with women.
On Aug. 20, 2015, Canadian-based Valeant Pharma announced it had acquired Sprout for $1 billion in cash and a share of future milestone payments. Sprout will stay in Raleigh and Cindy Whitehead, chief executive officer and co-founder of Sprout, will continue to run the company, but as a division of Valeant.
