Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials

This article presents the results of the two pivotal RECONNECT clinical trials (Studies 301 and 302), randomized, double-blind, placebo-controlled, that evaluated the efficacy and safety of bremelanotide for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. The studies included a total of more than 1,200 women randomized to self-administered bremelanotide 1.75 mg subcutaneous or placebo, as needed, before anticipated sexual activity, for 24 weeks.

The co-primary endpoints were the change in the Female Sexual Function Index — desire domain (FSFI-D) score and the Female Sexual Distress Scale — Desire/Arousal/Orgasm (FSDS-DAO). Both studies achieved statistical significance on both endpoints.

Key results:

• Significant increase in sexual desire as measured by FSFI-D compared to placebo
• Significant reduction in distress associated with low libido
• Improvement observed from the first weeks of treatment
• Nausea was the most common adverse effect (~40% of patients), but decreased with continued use
• No significant cardiovascular adverse effects at the approved dose

Bremelanotide acts as an agonist of melanocortin receptors MC4R and MC3R in the central nervous system, modulating neural circuits involved in sexual desire. This central mechanism differentiates it from treatments acting peripherally. The results of these trials were fundamental for the FDA approval of bremelanotide (Vyleesi) in June 2019, making it the second approved therapy for female HSDD and the first with on-demand subcutaneous administration.