FDA approves a new drug for increasing libido in premenopausal women

Courtesy: AMAG Pharmaceuticals

The US Food and Drug Administration (FDA) recently approved bremelanotide (Vyleesi, AMAG Pharmaceuticals), for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women.

Vyleesi, a melanocortin receptor agonist that comes as autoinjector, joins flibanserin(Addyi, Sprout Pharmaceuticals) as the class of drugs approved by the FDA for the treatment of acquired HSDD. Flibanserin is Serotonin 5-HT-Receptor Agonists and is taken orally.

HSDD is the most commonly prevalent female sexual dysfunction and is largely under-recognized and undertreated. It is believed that approximately 9% of all premenopausal women in the United States experience it but less than half of these patients seek help or initiate discussions with physicians.

 “Women with HSDD often avoid situations that could lead to intimacy, the impact of which goes far beyond the bedroom and can often result in anxiety, loss of vitality, self-esteem issues and relationship stress. It is important that women suffering from this condition have a choice of treatment options available to them,” quote Anita H. Clayton, M.D., Chair, Department of Psychiatry & Neurobehavioral Sciences, University of Virginia School of Medicine, VA in an AMAG Pharma news release.

The upside of bremelanotide is women need to use it as required as opposed to flibanserin which must be consumed daily.  The drug is dispensed as prefilled autoinjector pen which has to be self-administered by the woman into her abdomen or thigh at least 45 minutes before anticipated sexual activity and can be taken at any time of day.

Courtesy: AMAG Pharmaceuticals

Patients should not use more than one dose within 24 hours or more than eight doses per month. Patients should discontinue treatment after eight weeks if they do not report an improvement in sexual desire and associated distress.

While the exact mechanism of action is still unknown, the drug is believed to act on the melanocortin receptors in the central nervous system that are thought to be associated with sexual function.

The FDA approval of Vyleesi is based upon data from approximately 1,247 women in two pivotal (NCT02333071 and NCT02338960), replicate, double-blind placebo-controlled Phase 3 trials (RECONNECT). Most patients used the drug 2-3 times a month with no more than once a week.

Vyleesi does not enhance sexual performance, but there was a statistically significant increase in desire and decrease in distress at the time of intimacy. Women in both the trials didn’t experience any problem with the autoinjector.

The most common side effects of Vyleesi are nausea and vomiting, flushing, injection site reactions, and headache. An increase in blood pressure was also noted, which usually resolved in 12 hours. Hence, Vyleesi is contraindicated in patients at high risk of cardiovascular disease and those with high-blood pressure.

Vyleesi is not indicated for the treatment of HSDD in postmenopausal women or in men. AMAG is expected to make Vyleesi commercially available in September 2019 through select specialty pharmacies.

FDA press release

AMAG Pharmanews release

Another novel drug for female hypoactive sexual desire shows promising results in phase III trials.

Women who are distressed because of hypoactive sexual desire could soon find relief because of a new drug, Bremelanotide (BMT).

Female Sexual Dysfunctions (FSD) encompasses multifactorial entities affecting about 10% of the population. Few treatment options exist to treat this condition.

auto-injector for Bremelanotide, Palatine Technologies

Bremelanotide, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. It increases levels of dopamine and norepinephrine in medial preoptic area, thereby,  modulating the  brain pathways involved in sexual response.

The results of two phase III trials were presented as a poster at the American Society of Clinical Psychopharmacology (ASCP) annual meeting, Florida May 29 – June 2, 2017.

The RECONNECT study comprises 2 Phase 3, multicenter trials involving 1,247 premenopausal women with low sexual desire. The women were in stable, monogamous relationship.

In this intent to treat study, the women underwent a month screening period and a month of treatment with a placebo so that the investigators could have an idea about various baseline scores.

Women were randomized to nearly 6 months of treatment with either self-administered BMT (1.75 mg) or placebo subcutaneously using an auto-injector, as-desired, prior to sexual activity. This was followed by an open label 52 weeks extension.

The control and cases were assessed on various indices like the desire domain of the Female Sexual Function Index (FSFI-D) and the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) score for feeling bothered by low sexual desire; FSDS total and bother scores; Women’s Index of Treatment Satisfaction (WITS-9) score; self-assessment of benefit, and satisfying sexual event (SSE) items of the Female Sexual Encounter Profile-Revised (FSEP-R).

Besides significantly improving the scores of all the indices, the women on BMT showed a significant improvement in number of satisfying sexual events, arousal, lubrication and orgasm. The women also reported feeling less distressed and more satisfied with their sexual relations.

Most common side effects encountered were nausea, vomiting, flushing, or headaches resulting in 18% of women to discontinue the drug as compared to 2% in placebo group.

The average age of the study participants was 39 years, more than 80% were white with a mean BMI of 28.7 kg/m2 and most of them were suffering from hypoactive sexual desire disorder (HSDD) with decreased arousal.

In 2015, FDA approved the little pink pill or 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.

The authors concluded, “Treatment with BMT is associated with clinically meaningful and statistically significant improvement in desire and a decrease in distress; both hallmark characteristics of HSDD. BMT is an efficacious treatment for key aspects of sexual function — desire, arousal, lubrication, and orgasm, in premenopausal women.”

All the poster abstracts at the conference can be accessed here.