The US Food and Drug Administration (FDA) today approved bremelanotide (Vyleesi, AMAG Pharmaceuticals), a first-in-class melanocortin 4 receptor agonist for hypoactive sexual desire disorder (HSDD) in premenopausal women.

It joins flibanserin (Addyi, Sprout Pharmaceuticals), the only other FDA-approved HSDD treatment for premenopausal women.

The FDA had until June 23 to complete the review of bremelanotide's new drug application (NDA) under the Prescription Drug User Fee Act (PDUFA).

HSDD affects approximately 10% of all premenopausal women in the United States, or about 6 million women, said Julie Krop, MD, chief medical officer and executive vice president of medical development and regulatory affairs at AMAG Pharmaceuticals.

"It is largely underrecognized," Krop told Medscape Medical News. "These women have issues with their relationships; they often have issues concentrating at work and image difficulty. The effects extend way beyond the bedroom."

Women and some physicians typically don't see it as a medical condition that can be treated. The women feel they are somehow "broken," Krop said.

"It's similar to how depression was years ago — stigmatized and not really known to be a physiologic condition," she said.

Self-Administered With Autoinjector

Bremelanotide is designed to be self-administered subcutaneously with a disposable autoinjector at least 45 minutes before an anticipated sexual encounter, Krop said. Users don't see the needle and it can be pushed against the abdomen or thigh, she said.

It has a novel mechanism of action that adjusts the balance between the neural pathways that excite and inhibit to restore sexual desire.

Krop said AMAG expects the drug to be available by September, which is National Sexual Health Awareness month.

Bremelanotide was studied in two replicate phase 3 trials with more than 600 patients each, testing for both increase in desire and reduction in distress, the hallmarks of HSDD.

"We saw statistically significant and clinically important improvements in both those parameters," Krop said.

The most common adverse events were nausea, flushing, and headache.

Women in the trials tolerated autoinjection very well, Krop said. "Ninety percent of them said they did not experience any difficulty."

AMAG Pharmaceuticals licensed bremelanotide from Palatin Technologies, Inc, in February 2017.

More Options Critical

Anita Clayton, MD, chair of the Department of Psychiatry and Neurobehavioral Sciences, and professor of clinical obstetrics and gynecology at the University of Virginia Health System in Charlottesville, said having more options is crucial for women.

She compared bremelanotide with already-approved flibanserin, which is taken every night at bedtime, and acts through specific serotonin receptors (5-HT 1A agonism and 5-HT 2A antagonism) to reduce serotonin inhibition of sexual desire and arousal.

Each of the drugs works in about 50% of premenopausal women with HSDD, she told Medscape Medical News.

Clayton said there's no easy way to determine whether a woman has increased serotonin inhibition, reduced excitatory activity, or both. If her serotonin inhibition is increased, flibanserin may be best, Clayton said, but if excitatory activity has dropped, bremelanotide may be better.

If it's both, "maybe a combination would be helpful, but it's not yet been studied," she said.

"Other medications are being studied, and I hope they also are approved so women have multiple options," Clayton added.

Also, some women may prefer daily dosing to have desire consistently (flibanserin), while some may prefer it just around the times when they desire sexual activity (bremelanotide), she noted.

"The side effects are generally well tolerated for both drugs. With flibanserin, the sedation is not a big problem as the drug is taken at bedtime. In fact, some women like the improved sleep," she said. "Neither drug causes weight gain."

Fred Wyand, director of communications for the American Sexual Health Association/National Cervical Cancer Coalition, told Medscape Medical News, "We believe women have a right to sexual pleasure and satisfaction and there are few options available for women with sexual difficulties. Society is still conflicted about female sexuality to begin with, and it's gratifying to see some movement to recognize — and act on — issues of sexual functioning, though the pace is a bit slow."

Krop is chief medical officer and executive vice president of medical development and regulatory affairs at AMAG. Clayton is a consultant to Sprout Pharmaceuticals and AMAG/Palatin Therapeutics. The American Sexual Health Association/National Cervical Cancer Coalition has received support from AMAG for a project on sex and aging.

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