Research Evidence
RECONNECT Phase III Trials
The approval of Vyleesi was based on two identical Phase III, randomized, double-blind, placebo-controlled, multicenter trials (RECONNECT) evaluating bremelanotide 1.75 mg versus placebo in 1,267 randomized premenopausal women with acquired, generalized HSDD. Patients were randomized 1:1 to 24 weeks of on-demand treatment.
The coprimary efficacy endpoints were change from baseline to end-of-study in the Female Sexual Function Index desire domain score (FSFI-D) and the Female Sexual Distress Scale Desire/Arousal/Orgasm item 13 (FSDS-DAO-13).
Both studies met both coprimary endpoints. In the integrated analysis, bremelanotide produced statistically significant increases in sexual desire (P < 0.001) and statistically significant reductions in distress related to low sexual desire (P < 0.001) compared to placebo. Approximately 25% of patients treated with bremelanotide achieved an increase of 1.2 or more in their desire score, compared to approximately 17% of placebo-treated patients. Benefits were consistent across age, weight, and body mass index subgroups.
Long-Term Extension Data
An open-label extension study assessed long-term safety and efficacy beyond the initial 24-week trial period. Results demonstrated that improvements in desire and reductions in distress were maintained with continued on-demand use, and no new safety signals emerged with prolonged exposure.
Male Erectile Dysfunction Studies
A randomized, double-blind, placebo-controlled trial evaluated bremelanotide in men with erectile dysfunction, demonstrating positive clinical responses in 33.5% of bremelanotide-treated patients versus 8.5% on placebo. A separate salvage study in sildenafil non-responders showed that bremelanotide co-administered with sildenafil produced significantly enhanced erectile responses compared to sildenafil alone.
Palatin Technologies initiated a Phase II study of bremelanotide co-administered with a PDE5 inhibitor for erectile dysfunction in men who do not respond to PDE5 inhibitor monotherapy. Results from this ongoing program will inform whether bremelanotide receives a future male indication.
Early Phase Research
Phase I and II studies by Molinoff et al. and Diamond et al. established the proof of concept for melanocortin agonists in sexual dysfunction, demonstrating dose-dependent effects on subjective arousal and physiological measures in both men and women. These early studies confirmed the central mechanism of action and informed the dose selection for the pivotal Phase III program.