FDA clears a controversial female libido drug despite 'modest' effects and dangerous risks

Sprout Pharmaceuticals CEO Cindy Whitehead

The FDA cleared Sprout Pharmaceuticals' much-scrutinized flibanserin, a first-of-its-kind pill designed to boost women's sexual desire, but not without sticking a black-box safety warning on the twice-rejected drug.

The drug, to be sold as Addyi, is approved to help premenopausal women diagnosed with hypoactive sexual desire disorder (HSDD) regain their sex drives by boosting dopamine and norepinephrine levels in the brain. The FDA's decision follows two prior rejections over what the agency described as "modest" efficacy combined with some alarming safety signals. Following the second denial, Sprout conducted three new drug-interaction studies, apparently satisfying regulators in the process.

Addyi will ship with a boxed warning detailing the drug's risks of severe low blood pressure and fainting spells, side effects that are exacerbated by alcohol use, according to the FDA. The agency is demanding doctors "assess the likelihood of the patient reliably abstaining from alcohol" before doling out Addyi, and regulators are requiring all would-be prescribers to complete a training program. The agency mandated that Sprout conduct three post-marketing studies to shed light on how the drug is interacting with alcohol in real-world settings, and the company has promised not to advertise Addyi for 18 months to avoid generating dangerous hype.

The company plans to launch Addyi in October, and CEO Cindy Whitehead estimates it will cost women with insurance about $30 to $75 a month. It remains unclear whether payers will reimburse for the drug.

Addyi's path to approval has been beset by controversy, as physicians and public health commentators have openly questioned whether it actually works, while advocacy groups point out the FDA has approved more than 20 drugs for erectile dysfunction but never cleared a treatment for female sexual desire disorder. Sprout has funded an organization called Even the Score, which has agitated for Addyi's approval, while the FDA has repeatedly denied any gender bias in its past decisionmaking.

Sprout's drug, invented by Boehringer Ingelheim, endured its first rejection in 2010 after failing to significantly beat out placebo in increasing patient-reported sexual desire, tracked with a daily electronic diary, across two Phase III trials. Addyi did chart a statistically significant improvement in desire as measured by the Female Sexual Function Index (FSFI), but the FDA and its advisers made clear their preference for the diary method.

Sprout then picked up where Boehringer left off, running a Phase III trial of its own with co-primary endpoints of FSFI improvement and an increase in patient-reported satisfying sexual encounters, or SSEs. The study met its goals, but the positive effects were "modest," the FDA said at the time; that, coupled with the agency's skepticism about FSFI and a bevy of safety issues, led to the drug's second rejection.

Sprout regrouped last year, running a handful of Phase I trials designed to address concerns about Addyi's interaction with other drugs and its effect on patients' ability to drive the morning after use. The whole package was enough to win over the majority of the FDA's independent advisory panel, which voted 18-6 in favor of approving the drug at a June meeting.

"Today's approval provides women distressed by their low sexual desire with an approved treatment option," FDA drug approval chief Janet Woodcock said in a statement. "The FDA strives to protect and advance the health of women, and we are committed to supporting the development of safe and effective treatments for female sexual dysfunction."

- read the statement