After a long and controversial process, the US Food and Drug Administration (FDA) has approved the first-ever drug aimed at boosting female libido.
"Today's approval provides women distressed by their low sexual desire with an approved treatment option," said Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, in a statement.
Flibanserin (Addyi) — also known as "Female Viagra" or "Pink Viagra" — will be marketed by Sprout Pharmaceuticals. It is approved to treat premenopausal women. The nonhormonal therapy — a 5-hydroxytryptophan (HT)(1A) receptor agonist and 5-HT(2A) receptor antagonist — was approved for hypoactive sexual desire disorder (HSDD). The HSDD diagnosis appeared in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-4), but was subsumed into a larger category of Female Sexual Interest/Arousal Disorder in the latest edition, DSM-5.
Sprout said that up to one in 10 women have HSDD.
The once-daily 100-milligram tablet is to be taken at bedtime, and alcohol use will be contraindicated due to common side effects including drowsiness and dizziness. The label will include a boxed warning about the potential for increased hypotension or syncope with alcohol. The FDA is requiring Sprout to conduct three postmarketing studies in patients to better understand the interaction between flibanserin and alcohol. Concomitant use with moderate-to-strong CYP3A4 inhibitors — such as antifungals — will also be contraindicated and included in the boxed warning.
"Because of a potentially serious interaction with alcohol, treatment with Addyi will only be available through certified health care professionals and certified pharmacies," Dr Woodcock said.
According to Sprout, any licensed prescriber will be able to prescribe flibanserin as long as they are certified in the risk evaluation and mitigation strategy (REMS) program. Certified prescribers must counsel patients using a Patient-Provider Agreement Form about the increased risk for severe hypotension and syncope and the importance of not drinking alcohol when taking flibanserin, said the FDA.
Pharmacists must also complete the program, which includes reading the flibanserin REMS Training Program and full prescribing Information, answering knowledge assessment questions online and completing the attestations, and completing a form to enroll in the REMS Program.
Clinician Education to Be Focus
"HSDD is a very real problem for women," Leah Millheiser, MD, director of the female sexual medical program at Stanford University School of Medicine, told Medscape Medical News. Dr Millheiser said that the condition is caused by an imbalance in neurotransmitters, and that "there is absolutely a need for a drug that's been shown to be safe and effective."
The data showed that true responders had six to eight additional sexual events per month, Dr Millheiser said. She said that she hoped the approval would lead to more "clinicians getting educated about HSDD."
Sprout Chief Executive Officer Cindy Whitehead agreed, saying that the company's postapproval focus would be on education. "We know there's a lot of demand and a lot of interest in this product," she told Medscape Medical News. The company's aim is "to have a conversation about facts and scientific evidence and expectation-setting."
At the same time. the road to approval "has been a long process," said Whitehead.
Sprout aims to start selling flibanserin on October 17, said Whitehead. She did not give a specific price, but said that the drug would likely be available under insurance plans for a $30-to-$70 per month co-pay — the same monthly cost as for erectile dysfunction drugs.
Initially, the company will use 200 sales representatives to detail clinicians already familiar with diagnosing HSDD — primarily obstetricians and gynecologists. Some psychiatrists and primary care physicians will also be included, she said.
Some Dissatisfied With Drug
Others were not so happy with the idea of a flibanserin approval.
Hundreds of advocates and scientists have written to the FDA in recent weeks alleging that Sprout had mounted a public relations campaign that glossed over safety and effectiveness concerns in an effort to win approval.
One group — which included 103 signatories — said that the drug posed risks in particular to women who drank alcohol. Another group of 133 psychiatrists, psychologists, sex therapists, and sex educators, disputed how Sprout characterizes low female libido and how it should be treated.
The letter writers also objected to "Even the Score," a campaign that began in June 2014 and received some of its funding from Sprout. The campaign invited visitors to its website and Facebook pages to sign a petition to the FDA and to write their congressman.
Several members of Congress did urge the FDA to approve flibanserin — first in 2014, led by Reps. Debbie Wasserman Schultz (D-FL), Chellie Pingree (D-ME), Nita Lowey (D-NY), and Louise Slaughter (D-NY), and then again in March 2015, led by Rep. Jackie Speier (D-CA), according to an Even the Score press release.
A Long Road to Approval
Flibanserin, originally developed as an antidepressant, had a long road to approval. Boehringer Ingelheim sought approval for the drug initially; the FDA's Advisory Committee for Reproductive Health Drugs voted 10 to 1 against approval in June 2010. Sprout then acquired the rights, but the FDA subsequently rejected approval again. Sprout appealed, and the agency eventually agreed to a new advisory panel meeting.
A joint meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 18 to 6 to back approval in June 2015.
In the pivotal trial, 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. Fifty-one percent of patients taking flibanserin said their desire had improved, but 38% of placebo patients indicated the same.
The flibanserin label will note that if a woman is not responding after 8 weeks of daily dosing, the therapy should be discontinued, said Whithead.
Dr Millheiser is the chief scientific officer of Nuelle, a women's sexual health company that has developed a hands-free accessory designed to elicit sexual arousal.
