Advisory Committee Endorses Sprout’s Female Sexual Dysfunction Drug

Members of the FDA’s Bone, Reproductive and Urologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee voted 18-6 last week to recommend approval of Sprout’s female sexual dysfunction drug, despite lingering safety concerns.

FDA regulators expressed hesitations about the drug in premeeting briefing materials. While the agency did not doubt that Addyi (filbanserin) leads to more satisfying sexual events and reduces distress, officials were concerned about the drug’s risks when combined with alcohol.

Kimberly Lehrfeld of CDER’s Division of Risk Management told the committees that the FDA could warn patients about negative interactions with drugs like antidepressants and anticonvulsants in the product labeling, but that the risk of concomitant alcohol use would require a stronger risk-management plan.

All of the panelists agreed, with none voting to approve the drug with just labeling to manage its risks. The 18 advisors who voted in favor of Addyi recommended that stronger risk management plans be required for approval.

Walid Gellad, of the University of Pittsburgh, recommended instituting a risk evaluation and mitigation strategy, noting that should the FDA approve the drug, it will likely be used off-label in populations Sprout hasn’t studied.

Sprout has proposed a REMS that includes a medication guide and a communication plan, but Lehrfeld said this is too passive, because it wouldn’t be subject to any kind of FDA oversight and could be discontinued at any time.

The agency is recommending three possibilities:

• A plan to communicate the risks of fainting and injury to prescribers;
• The communication plan, plus a pharmacy certification plan that would require that pharmacists be trained to warn patients of safety risks when they dispense Addyi; or
• A pharmacy certification program along with a prescriber certification program that would require prescribers acknowledge reading the risks of the drug and the need to communicate those risks to patients.

While many of the advisors agreed that prescriber and pharmacy certification plans are appropriate parts of a REMS, others said a postmarketing study would better elucidate the real-time risks over longer periods of time.

A number of panelists warned against overemphasizing the risk of alcohol interaction, saying other drugs like metronidazole, which is indicated for pelvic infections, can also have serious side effects when combined with alcohol.

Robert Silbergleit, of the University of Michigan, noted that the incidence of alcohol-related adverse events in an efficacy trial that enrolled women who were social drinkers was no greater than that in Sprout’s alcohol-interaction trial, which enrolled mostly men.

This is Addyi’s third go-round with the FDA. The agency originally passed on Addyi in 2010, after a committee said the benefits didn’t outweigh the risks. Boehringer Ingelheim, which developed the drug, sold it to Sprout, which conducted more trials prior to resubmitting its NDA. The FDA rejected the drug a second time in 2013. — Lena Freund