An FDA advisory panel on Thursday recommended approval of the first drug to be indicated for hypoactive sexual desire disorder (HSDD) in premenopausal women—a treatment rejected by the agency twice previously.
Filbanserin, a once-daily non-hormonal pill to be marketed as Addyi by Sprout Pharmaceuticals, was recommended 18 to 6 by a tandem of the FDA’s Bone, Reproductive and Urologic Drugs Advisory Committee, and the agency’s Drug Safety and Risk Management Advisory Committee.
The combined panel, however, added that filbanserin’s label must include language alerting users of the need to manage side effects that include fainting, low blood pressure, nausea, and fatigue. Panelists also advised the agency to require Sprout to carry out postmarketing safety studies, establish a patient registry, and require that physicians be certified—with pharmacies confirming such certification—before being allowed to prescribe filbanserin.
The FDA usually follows the recommendations of its advisory committees, though the agency is not required to do so. If the agency follows customary practice and approves filbanserin, it will reverse two previous FDA setbacks for the drug.
The first came in 2010 when the predecessor to the Bone, Reproductive and Urologic Drugs Advisory Committee recommended against filbanserin; the Advisory Committee on Reproductive Health Drugs cited insufficient evidence of efficacy. Soon after, original developer Boehringer Ingelheim—which repositioned filbanserin from an antidepressant—sold its rights to the compound the following year to Sprout, a startup launched with $20 million.
After the FDA’s second rejection in 2013, Sprout appealed the decision, resolving its dispute with the FDA after conducting, at the agency’s request, a Phase I pharmacokinetic study and a Phase I driving study. Results from both were included in Sprout’s NDA submitted in February.
That NDA also cited data from three Phase III trials, all showing a statistically significant for the drug compared to placebo in the number of satisfying sexual events and in distress related to sexual desire, according to the FDA.
While the first two trials did not show statistically significant improvement over placebo in the co-primary endpoint for sexual desire, they showed statistically significant improvement over placebo for a secondary endpoint that used the Female Sexual Function Index (FSFI) to assess sexual desire. The third trial used FSFI as the pre-specified co-primary endpoint for sexual desire and showed a statistically significant improvement over placebo, consistent with the FSFI findings in the two earlier trials, the agency said.
Sprout also began a successful-to-date lobbying campaign for filbanserin, joining with 24 organizations ranging from the National Organization for Women to the women’s health equity group Even the Score. They accused the FDA of holding the compound to a higher standard than male sexual disorder treatments such as Cialis and Viagra, and thus practicing gender bias.
“The FDA rejects claims of gender bias,” countered Hylton Joffe, M.D., M.M.Sc, director of the agency’s Division of Bone, Reproductive and Urologic Products, in a briefing report prepared for the combined panel. “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.”
Some advocacy groups, however, echoed the FDA and expressed concern that the drug had not shown sufficient effectiveness to warrant approval: “The problem with this drug is not gender bias at the FDA but rather the drug itself,” Cindy Pearson, executive director of the National Women’s Health Network, said Wednesday in a statement. “We recognize that a lack of sexual desire can be a distressing problem for women. We also believe that it might be possible to develop a drug that is effective for some of women’s sexual problems.”
Flibanserin is both a 5HT1A receptor agonist and a 5HT2A receptor antagonist. The drug is designed to help to balance the neurotransmitters dopamine and norepinephrine that influence sexual desire and to decrease serotonin, which is responsible for sexual satiety and inhibition.