Novel female sexual dysfunction drug effective, phase III studies show

MIAMI – Women distressed by a low desire for sex could have a novel pharmaceutical intervention soon.

Phase III results from the two Reconnect studies of 1,247 premenopausal women with hypoactive sexual desire disorder in stable relationships showed that bremelanotide was associated with statistically significant improvements in sexual desire and levels of distress about hyposexuality, compared with placebo. The phase III results confirm a phase IIb randomized, double-blind, multicenter trial showing that the drug boosts sexual arousal and desire in this population.

Anita H. Clayton, MD

The phase III data were presented in a poster and during a session dedicated to new drugs in the pipeline at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Bremelanotide, administered subcutaneously, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. The mechanism of action is thought to be analogous to a peptide alpha-melanocyte–stimulating hormone that is thought to enhance dopamine and norepinephrine, said Dr. Clayton, the David C. Wilson Professor of Psychiatry and Neurobehavioral Sciences, and professor of clinical obstetrics and gynecology at UVA.

Women in the modified, intent-to-treat study were all given a 1-month, no-drug qualification month, followed by a 1-month single-blind placebo treatment, before they were randomly assigned to 24 weeks of either placebo or 1.75 mg bremelanotide. They could choose to use the drug at their discretion, whenever they anticipated that they would like to have sex.

“Women, on average, had sex about four times a month and used the product three times a month,” Dr. Clayton said in an interview. “We don’t have the answer for [why], but the likelihood is that they used it, and then, when they did, they had more desire and so didn’t need to [use it every time]. But, they could have used it every day of the month if they wanted.”

Changes in Female Sexual Function Index (FSFI) scores from baseline to study’s end were 0.24 in the 316 placebo group, compared with 0.54 in the 314 women in the study drug arm of the first study (P less than .0002). In the second study, the 290 women given placebo had a 0.21 improvement in FSFI scores, compared with a 0.63 improvement in the 282 study drug arm (P less than .0001). The FSFI is a validated, 19-item measure of female sexual function across several domains, including arousal and desire, from the past 30 days. Higher scores indicate better sexual function.

Reductions in distress levels as measured by the Female Sexual Distress Scale: Desire, Arousal, Orgasm (FSDS:DAO), item #13, were –0.35 in the placebo group of the first study, compared with –0.74 in the drug arm (P less than .0001). In the second study, the placebo arm had a –0.42 shift in scores from baseline, compared with –0.71 in the study drug arm (P less than .0057). The FSDS:DAO is a validated, 15-item Likert scale that measures aspects of distress surrounding aspects of sexual functioning in the past 30 days.

Across several secondary patient-reported outcomes study wide, when compared with placebo, the women who had been given bremelanotide reported higher levels of perceived benefit for having been in the study and higher levels of overall satisfaction with their sexual relations while taking the intervention. Changes in pain levels experienced during sex and differences from placebo in the number of satisfying sexual events, as defined by the individual woman, were not statistically significant. However, across the combined study arms, the reported number of satisfying sexual events was numerically better than placebo.

“That just means that ‘satisfying sexual events’ is not a very specific measure in studies of HSDD,” Dr. Clayton said, noting that the Food and Drug Administration no longer requires it as a primary endpoint in the most recent guidance on female sexual dysfunction. “[It’s] nonspecific. Some women think, ‘Yeah, I had a satisfying event because I had an orgasm. Others think it’s because they actually wanted to participate in sex, and that was so much better for them than going along with it but thinking, ‘Just get it over with.’ ”

Mild to moderate treatment-emergent adverse events led 18% of women in the combined drug study groups to either discontinue or interrupt treatment, mostly because of nausea, vomiting, flushing, or headaches. This was in comparison to discontinuation or interruption in 2% of the women in the combined placebo arms.

Because all study participants, whose average age was 39 years, were screened for depression and relationship problems, Dr. Clayton said the causes of HSDD in the study cohort were “biologically based” but that hypoactive sexual desire disorder is a biopsychosocial condition.

“These were women who were in a relationship for at least 6 months and had previously had at least 2 years of what they considered adequate or satisfactory sexual desire and function,” Dr. Clayton said. “My experience with these patients is that they are in love with their partners, they agree on their values, they communicate. But, what’s happened is they biologically and physiologically don’t desire sex anymore.”

In 2015, the FDA approved flibanserin (Addyi) a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, as the first treatment for hypoactive sexual desire disorder in premenopausal women. Flibanserin, a central acting medication that is taken as 100 mg daily, is marketed by Valeant.*

The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin, Valeant, and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

* Clarification, 6/21/2017: An earlier version of this story misstated the name of the company marketing Addyi and one of Dr. Clayton’s disclosures. The name of that company is Valeant.