Five weeks from now, the FDA will face a deadline for making a final marketing decision on flibanserin, a drug designed to treat sexual desire disorder in women. Already a two-time loser at the agency, Sprout Pharmaceuticals--which acquired the treatment from a frustrated Boehringer Ingelheim--managed to make a comeback recently and snag an important 18 to 6 FDA panel vote in its favor. And whatever the FDA officially concludes, the decision will come down as one of the most controversial of the year.
An editorial in JAMA this week from three of the advisory panel members underscores the deep-seated opposition to this drug, flagging some serious concerns about a possible green light from the FDA this summer. The trio are especially troubled by the lobbying and social media campaign--an increasingly popular tool to help push for FDA action these days--Sprout helped engineer to put pressure on the FDA and its advisers to give them a green light.
The three panel members--Walid Gellad of the University of Pittsburgh, the Medical College of Wisconsin's Kathryn Flynn and G. Caleb Alexander from Johns Hopkins--noted concerns about the unimpressive and marginal improvement in the number of satisfying sexual events per month reported when the drug was compared against a placebo response. The panel, they added, never discussed much about the way Sprout used patient-reported data to establish an increase in sexual desire for the primary efficacy endpoint, switching from a daily diary to a questionable four-week recall method using a desire subscale of the Female Sexual Function Index [FSFI] in a follow-up study.
What was discussed was the likelihood of off-label drug use among a broad group of women who won't have the same profile as the subjects evaluated in the drug studies or even likely qualify for hypoactive sexual desire disorder (HSDD), which still troubles the authors. And then there are lingering concerns about hypotension, syncope (fainting) and somnolence.
To get back to the FDA with a third approval attempt, Sprout only had to complete new safety work, without any added snapshot on efficacy.
"Although the driving study was reassuring," they noted, "isolated comparisons of safety across products can be misleading because FDA product reviews are not fundamentally comparative in nature. Notably, the alcohol interaction study took place in a sample of 25 healthy volunteers, only 2 of whom were women."
But Sprout didn't just go back to complete a new safety study to help alleviate regulators' concerns about what could happen with this drug. The biotech is also closely linked with Even the Score, a lobbying group aimed at persuading the FDA and lawmakers that it was time the agency delivered for women, after repeatedly approving drugs for male sexual dysfunction.
"The group, initially created through the efforts of a consultant to flibanserin's manufacturer who formerly directed the FDA's Office of Women's Health, promoted the claim that there are 26 approved medications for male sexual dysfunction but none for women," the panelists write in JAMA. "The claim has been rejected by the FDA, because there are no approved products for low sexual desire in men, and the 26 medications include multiple formulations of testosterone. Although flibanserin is not the first product to be supported by a consumer advocacy group in turn supported by pharmaceutical manufacturers, claims of gender bias regarding the FDA's regulation have been particularly noteworthy, as have the extent of advocacy efforts ranging from social media campaigns to letters from members of Congress."
Against that "politically charged atmosphere," the FDA gets to decide one way or the other whether, and how, flibanserin can be marketed. And either way they choose to go, critics on both sides will be ready to leap.