The U.S. Food and Drug Administration (FDA) approved bremelanotide (Vyleesi, AMAG Pharmaceuticals) to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. HSDD is characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship or the effects of a medication or other drug substance. Bremelanotide, a melanocortin 4 receptor agonist, is administered subcutaneously with an autoinjector and is the first treatment for this patient population that can be self-administered as needed in anticipation of sexual activity.
The FDA approval of bremelanotide is based upon data from 1,247 women in two Phase 3 (RECONNECT) trials, Study 301 and Study 302. The Phase 3 RECONNECT Studies consisted of two double blind placebo-controlled, randomized parallel group studies comparing a subcutaneous dose of 1.75 mg bremelanotide. The two trials consisted of 1 4-week screening period and a Core Phase (4-week at-home placebo, and 24-week randomized, double-blind treatment periods). Participants self-administered 1.75 mg bremelanotide or placebo subcutaneously under the skin of the abdomen or thigh, as least 45 minutes before anticipated sexual activity. The co-primary endpoints were change from baseline to end-of-study in the Female Sexual Function Index desire domain (FSFI-D) score and change from baseline to end-of-study in the score for feeling bothered by low sexual desire, as measured by Item 13 of the Female Sexual Distress Scale ( FSDS-DAO). The FSFI-D 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. 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.
The FSFI-D-D showed a statistically significant increase for bremelanotide compared to placebo in both trials. In Study 301, 314 women were in the bremelanotide group and 316 were in the placebo group. The changes in FSFI-D scores from baseline to study’s end were 0.24 in the placebo group, compared with 0.54 in bremelanotide group (p < 0.0002). In the second study, Study 302, the 290 women given placebo had a 0.21 improvement in FSFI-D scores, compared with a 0.63 improvement in the 282 bremelanotide group (p < 0.0001). The FSDS-DAO item 13 also showed a statistically significant reduction in distress related to low sexual desire for bremelanotide compared to placebo in both trials. In Study 301, reductions in distress levels were –0.35 in the placebo group (n =316) compared with –0.74 in the bremelanotide group (n = 314; P < 0.0001). In Study 302, the placebo group had a –0.42 shift in scores from baseline (n = 290), compared with –0.71 in the bremelanotide group (n = 282; P = 0.0057).
In the both trials, the most common adverse events were nausea, flushing, injection site reactions, and headache. The majority of events were reported to be transient and mild-to-moderate in intensity. In clinical trials, bremelanotide caused small, transient increases in blood pressure, and is contraindicated in women with uncontrolled high blood pressure or known cardiovascular risk. Bremelanotide joins flibanserin (Addyi, Sprout Pharmaceuticals), the only other FDA-approved HSDD treatment for premenopausal women. Unlike flibanserin, bremelanotide does not seem to interact with alcohol.
» FDA Press Release
» AMAG Pharmaceuticals Press Release
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