FDA advisers recommend approval of libido drug for women

An advisory panel on Thursday recommended that the U.S. Food and Drug Administration approve the first-ever medication for premenopausal women with low libido, but only with special safety precautions.

The 18-to-6 vote was a victory for Sprout Pharmaceuticals, which has pugnaciously pushed for flibanserin - proposed brand name Addyi - despite two previous rejections by the FDA. After the last denial in 2013, the Raleigh, N.C., company and its allies created an Internet-based advocacy campaign dubbed eventhescore.org that accused regulators of sexism and a double standard.

After the vote, Sprout issued a subdued statement saying that "we look forward to continuing our work with the FDA."

The agency, which is expected to act by September, usually follows its advisers' recommendations.

The vote was a blow to a coalition of women's health activists who believe the FDA was right the first two times: flibanserin's risks - including drowsiness, fainting, and low blood pressure - don't outweigh its marginal effectiveness.

Cynthia Pearson, head of the National Women's Health Network, said the panel's daylong meeting showed the "many unresolved questions about the seriousness, severity, duration, and frequency of flibanserin's side effects," which can be worsened by "alcohol, birth control pills, and a host of other drugs."

Even advisers who voted for approval expressed ambivalence.

"The benefits are modest, maybe less than modest, but I'm afraid that puts [flibanserin] in good company with other approved drugs," said adviser Walid Gellad, codirector of the University of Pittsburgh's center for pharmaceutical policy. "I also have serious safety concerns."

Because of those concerns, the panel urged the FDA to bolster product label warnings by requiring a patient education program, and a certification program that doctors would have to complete to give the drug.

In its own safety proposals, Sprout said the product labeling should advise women to quit the drug if it doesn't work within 12 weeks. The company also promised not to do any direct-to-consumer advertising for the first 18 months, to let doctors learn about the drug.

The current staples of treatment for female sexual problems are psychotherapy and testosterone supplements. Dozens of women and doctors offered heartfelt testimony Thursday about the desperate need for better options. Drug companies, too, have been hotly pursuing a "pink Viagra" ever since the little blue pill for men was approved in 1998.

But female sex disorders have turned out to be far more difficult to define and quantify, let alone fix, than erectile dysfunction, which can be treated by improving blood flow. And while eventhescore.org claims men have dozens of approved sex drugs - an exaggeration that infuriates the campaign's critics - even men do not have an approved drug for low libido, medically known as "hypoactive sexual desire disorder."

Unlike Viagra, which is taken as needed, flibanserin must be taken daily, indefinitely.

Flibanserin, originally researched by German pharmaceutical firm Boehringer Ingelheim as an antidepressant, works on three brain chemicals.

Boehringer sold the rights to flibanserin to Sprout after the drug fell short in two major trials as a low-libido treatment.

Undeterred, Sprout did another big 24-week trial, in which flibanserin was slightly better than placebo on both crucial measures - increasing desire and the number of "satisfying sexual events."

To be precise, flibanserin increased monthly sex episodes by one more than placebo.

The FDA still rejected the drug in 2013 because, in rare but unpredictable cases, it can trigger low blood pressure or fainting, or both. That risk increases with common drugs that affect flibanserin's metabolism. Women in the trials were told not to take those drugs - a long list that includes certain antifungals, antibiotics, heart drugs, acid reflux pills, birth control pills, and antidepressants.

Even more worrisome, alcohol can increase the risks of fainting and low blood pressure.

After Sprout appealed the rejection, the FDA agreed to reconsider the drug if the company did studies to evaluate the dangers of drug interactions and alcohol.

On Thursday, the results of those studies troubled the advisers. Three out of 26 women given antifungals fainted or had low blood pressure, including one who became unresponsive and had to be rushed to a hospital. Those dangerous reactions also occurred in three out of 25 people given high doses of alcohol with flibanserin.

Only two of those 25 subjects were women because, the company said, it had trouble recruiting women who are moderate drinkers.

"We really know almost nothing about the clinical effects of women using this product with alcohol," said adviser Tobias Gerhard, a pharmacist and epidemiologist at Rutgers University.

Leonore Tiefer, a New York University psychiatrist and sex therapist who has harshly criticized eventhescore.org, said she hopes the FDA will override the panel's recommendation.

"It's a triumph of emotion over science," she said. "I think the committees were persuaded by the doctors who said they had 'nothing' to offer their patients. Absurd."

215-854-2720@repopter