FDA Panel Backs Approval of 'Female Viagra'

Alicia Ault

June 04, 2015

WASHINGTON, DC — Is third time a charm for "female Viagra"? After being rejected twice before, a US Food and Drug Administration (FDA) advisory committee voted today to back approval of flibanserin, which stands to become the first drug approved specifically for boosting female sexual desire.

Despite an 18-6 vote in favor of approval by the members of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, it was not a slam dunk for flibanserin, dubbed the female or "pink Viagra."

The drug's maker, Sprout Pharmaceuticals, was seeking FDA approval of once-daily, 100-milligram (mg) flibanserin for the treatment of hypoactive sexual desire disorder (HSDD) — as defined in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders — in premenopausal women. Sprout said that up to 7% of premenopausal women have HSDD.

"The benefits are modest, maybe less than modest," said panelist Walid Gellad, MD, MPH, associate professor of medicine at the University of Pittsburgh in Pennsylvania. "That puts it in good company with other approved drugs," said Dr Gellad, drawing laughter. But, he added, "I have serious, serious safety concerns."

He was not alone. Summing up the committee's view, panel chair Vivian Lewis, MD, said that the modest improvement meant that many women would still have the HSDD diagnosis. "However, even a modest improvement may be helpful clinically for someone who has HSDD," said Dr Lewis, professor of obstetrics and gynecology at the University of Rochester in New York.

The slight benefits barely outweighed the risks for most panelists — especially as many acknowledged that once the drug was approved, it would likely be used off-label in a much wider group of women. The committee told the FDA they'd like to see a Risk Evaluation and Mitigation Strategy for flibanserin that required prescribers to certify that they had been educated about the drug's risks and that they had counseled patients as well.

Some committee members urged the FDA to consider a boxed warning against using alcohol while taking flibanserin, while others wanted to see heightened warnings about drug-drug interactions when taking CYP3A4 inhibitors.

No Third Strike?

 

This was the third time that flibanserin had come before the FDA for approval. It was rejected by the agency after an advisory panel declined to recommend it in 2010. At that time, flibanserin developer Boehringer Ingelheim sold rights to Sprout. After a second rejection, Sprout appealed the decision. Although the agency said more studies were still required, it agreed to a new advisory committee meeting.

New efficacy data from a phase 3 study designed with the FDA's input showed that women had a 0.5 to 1 event per month additional satisfying sexual event (over baseline), and a 0.3 to 0.4 improvement (on a scale of 1.2 to 6) in the Female Sexual Function Index. They also had a mean 0.3 to 0.4 improvement on the Female Sexual Distress Scale (four-point scale) compared with placebo.

These were statistically significant improvements, said the FDA. But there also was a very large placebo effect, which led committee members to question the true magnitude of the drug's benefit. Fifty-one percent of patients taking the drug said their desire had improved, but 38% of placebo patients indicated the same.

Panelists also expressed disappointment with Sprout's study to assess the impact of concomitant alcohol use. There were only 27 participants and 25 of them were men. The FDA found that somnolence and dizziness increased when flibanserin was taken with alcohol, and that it escalated with higher doses of alcohol.

The agency said it was considering a boxed warning against alcohol use, which panelists agreed was necessary. Even with that warning, "it's going to be tough sledding in trying to prevent this drug from being used in women who drink," said panel member G. Caleb Alexander, MD, associate professor of epidemiology and medicine at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. Dr Alexander voted against approval.

The FDA also raised concerns about syncope and hypotension, saying that six women taking the 100-mg dose in Sprout trials had a fainting episode, with one resulting in a concussion. The company said that the central nervous system effects could be minimized by taking the drug at night, as recommended. It portrayed syncope and hypotension as rare, with 16 events recorded among some 4000 overall patients who have been exposed to flibanserin in trials.

Dr Gellad said that syncope should not be brushed off, as it could happen to anyone at any time, and that could lead to accidents.

A Demand for "Choice"

 

Given flibanserin's lengthy regulatory history — and the lack of approved libido-boosters for women — there was a long line of people at the hearing ready to tell their stories. Over an almost 2-hour public hearing, most speakers urged the FDA to approve the drug, and many accused the agency of gender bias and of being overly paternalistic, noting that many sexual dysfunction drugs had been approved for men, despite safety and efficacy concerns.

Hylton V. Joffe, MD, director of the FDA's Division of Bone, Reproductive and Urologic Products at the Center for Drug Evaluation and Research, said that the agency "firmly rejects this claim," and that the FDA considered HSDD an "unmet medical need," that deserved an approved therapy.

Among flibanserin's many backers was Irwin Goldstein, MD, president and director of the Institute for Sexual Medicine in San Diego, California, and also one of the first investigators to push sildenafil (Viagra, Pfizer) for erectile dysfunction. He said that the FDA had given men and their physicians a choice. "Women are capable of the same discussions with their providers," Dr Goldstein said. "Give women the right to choose."

Anita H. Clayton, MD, interim chair of psychiatry and neurobehavioral sciences at the University of Virginia Health System in Charlottesville, a consultant to Sprout, and a presenter at the 2010 advisory committee meeting, said that the efficacy was even clearer now, but that the FDA had found new safety issues. "Stop moving the goalpost," she told the agency.

But some still urged against approval.

Cindy Pearson, executive director of the National Women's Health Network, said that flibanserin's risks outweighed its efficacy. "The questions regarding alcohol use, nighttime dosing, drug-drug interactions, cannot be left unanswered," she said.

The FDA, however, usually follows its panels' advice.

Sprout said after the meeting that it was pleased. "With today's decision, we are one step closer to bringing to market the first treatment option for the most common form of female sexual dysfunction," said Sprout chief executive officer, Cindy Whitehead, in a statement. "We look forward to continuing our work with the FDA as it completes its review of our new drug application, including the discussion of a Risk Evaluation and Mitigation Strategy."

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