Addyi Sexual Desire Drug Received Dissent From Reviewers Before Approval

Addyi, the pill for premenopausal women with hypoactive sexual desire disorder, received FDA approval last month despite dissent from some reviewers that marginal clinical benefits did not outweigh the risks, an FDA summary said.

Reviewers were concerned about the lack of an alcohol interaction study in the target audience, pointing out that 23 of 25 subjects in the alcohol study were men. Given that the drug is taken at night before bed, and roughly half of all women drink alcohol, some interaction would have to be assumed.

The review notes that this was the third time Sprout Pharmaceuticals sought approval for Addyi (flibanserin), which was rejected in 2010 and 2013, giving precedent to three reviewers’ concerns.

Hylton Joffe, director of the FDA’s Division of Bone, Reproductive and Urologic Products, who recommended approving the drug, said package inserts and a box warning, along with requiring prescribing doctors and pharmacists to consistently warn women to avoid alcohol while taking the drug, was sufficient. He noted there is an ongoing alcohol interaction study involving women.

Joffe also recommended three additional alcohol intervention studies along with a pharmacovigilance study to evaluate risk of appendicitis as well as a pregnancy registry and maternal-fetal outcome study.

Responding to claims that such an alcohol study should have been conducted before approval, Joffe said that while not unreasonable, it was not required because flibanserin is being approved assuming that alcohol interaction in women is at least as severe as alcohol interaction in men.

Other concerns focused on the drug improving sexual desire in only 10 percent more patients than a placebo, claiming it did not offer enough benefit to warrant the risks such as low blood pressure and fainting.

Joffe said the results were consistent over three trials and ruled out a chance finding.

He also said that reporting “daily desire” through an electronic diary and measuring desire on the Female Sexual Function Index is not perfect, but that improvement seen in the number of sexual satisfying events and the decrease in distress related to low sexual desire was noteworthy.

Joffe concluded that flibanserin has a positive benefit/risk assessment, taking into account that there are no approved medications for HSDD — a condition that can cause substantial distress and have profound effects on relationships and well-being.

Given that some women had clinically meaningful response to the treatment and that major risks are mitigated with labeling along with postmarketing risk evaluation and mitigation strategies, the approval was warranted, he said.

The FDA approval proved to be beneficial to Sprout as Valeant Pharmaceuticals agreed to acquire the small North Carolina company for $1 billion.

To view the review summary, go to www.fdanews.com/09-18-15-AddyiSummary.pdf.  — Kellen Owings