The U.S. Food and Drug Administration has once again raised concerns about the safety of flibanserin, an experimental women's libido drug, saying it increased the risk of fainting and accidental injury, especially when combined with alcohol.
The review, published on the FDA's website on Tuesday, comes two days before a meeting of external advisers who will recommend whether it should be approved. The FDA typically follows the advice of its advisory panels.
The drug's developer, privately-held Sprout Pharmaceuticals, is seeking approval of flibanserin for premenopausal women whose lack of sexual desire causes distress. The proposed trade name of the product, if approved, is Addyi.
The FDA review found a statistically significant improvement in the number of satisfying sexual events (SSEs) experienced by women taking the drug and a reduction in distress related to low desire. There was an increase in desire as measured on a monthly, though not a daily basis.
The differences were numerically small, however, and the question remains whether the drug's benefits outweigh the risks, the FDA said.
From an average baseline of two to three SSEs a month, and after adjusting for an inevitable placebo effect, women had an increase of 0.5 to 1.0 SSEs a month. They had a placebo-adjusted improvement of 0.3-0.4 on the distress score, and a 0.3 to 0.4 increase in desire based on a score known as FSIAD, or female sexual interest/arousal disorder.
The agency has twice rejected flibanserin, saying its modest efficacy was outweighed by side effects, which also include nausea, dizziness and sleepiness.
The drug's arduous journey through the approval process has prompted accusations from some women's groups of a double standard and gender bias at the FDA. The agency has approved some two dozen drugs to treat male sexual dysfunction, and none for women.
"My fear is that should this large protracted long-term development of flibanserin fail, the category of women's sexual health will lose research and development support," Dr. James Simon, an expert in female sexual dysfunction who was a clinical trial investigator for flibanserin, said in a recent interview.
A testosterone patch to help improve female sexual dysfunction developed by Proctor & Gamble failed to win approval following a negative advisory committee meeting in 2004, and a testosterone gel from BioSante failed in clinical trials in 2011.
In a memo introducing the report, Dr. Hylton Joffe, director of the FDA's division of bone, reproductive and urologic products, said claims that the agency is holding drugs to treat female sexual dysfunction to more stringent standards for approval "are misleading and inaccurate."
"The FDA rejects claims of gender bias," he said. "The FDA's regulatory decision for each product is based on an assessment of whether the benefits outweigh the risks, and does not take gender into consideration."
Originally developed by Boehringer Ingelheim, flibanserin was first rejected in 2010 after an advisory panel said the benefits did not outweigh the risks.
Boehringer sold it to Sprout, which conducted additional studies and resubmitted the application. In 2013, the FDA again rejected it.
Flibanserin is a selective serotonin reuptake inhibitor, or SSRI, similar to a class of antidepressants that include Prozac. It was originally developed as an antidepressant but was not effective.