PT-141 — Bremelanotide

The strongest evidence comes from two large Phase 3 trials known as RECONNECT. The studies enrolled premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD). Participants self-administered subcutaneous bremelanotide 1.75 mg or placebo as needed during the 24-week double-blind treatment period.

Across both trials, bremelanotide produced statistically significant improvements in sexual desire scores and distress associated with low sexual desire compared with placebo. This is the evidence base supporting FDA approval.

In the two FDA registration trials, average change in the Female Sexual Function Index desire score was approximately +0.5 with bremelanotide versus +0.2 with placebo in Study 1, and approximately +0.6 versus +0.2 in Study 2. Distress related to low sexual desire also improved more with bremelanotide than placebo.

Importantly, FDA's label reports that there was no statistically significant improvement in the number of satisfying sexual events, which was a secondary endpoint. Therefore, an educational website should avoid presenting PT-141 as a guaranteed or dramatic “sexual performance enhancer.” Its approved benefit relates specifically to desire and distress associated with low desire in an appropriately diagnosed population.

Women completing the Phase 3 trials were eligible for a 52-week open-label extension. Among the 684 women who entered the extension, researchers reported continued improvements in sexual-desire and distress measures without identification of a new major safety signal during the extension period.

However, an open-label extension is less rigorous than a placebo-controlled trial because participants and investigators know treatment is being administered.

Bremelanotide was originally investigated for male erectile dysfunction. A placebo-controlled study evaluated intranasal PT-141 in healthy men and men with mild-to-moderate erectile dysfunction. At higher experimental intranasal doses, researchers reported significantly greater erectile responses compared with placebo, with onset occurring at approximately 30 minutes in some participants.

Another randomized study involved 342 men whose erectile dysfunction had not responded adequately to sildenafil. Positive clinical responses were reported in 33.5% receiving intranasal bremelanotide versus 8.5% receiving placebo. These studies establish genuine human research interest in male erectile function.

However, Vyleesi is not FDA-approved for men or for erectile dysfunction. The current label specifically states that it is not indicated for HSDD in men.

An early double-blind crossover study enrolled 18 premenopausal women diagnosed with female sexual arousal disorder. Researchers compared a single intranasal dose of bremelanotide with placebo and evaluated physiological and subjective responses to sexual stimulation.

These early studies helped lead to later development of subcutaneous bremelanotide for HSDD. They should not be interpreted as establishing PT-141 as a treatment for every form of female sexual dysfunction.

This is one of the most important distinctions. Bremelanotide is a melanocortin receptor agonist. FDA states that it activates several melanocortin receptor subtypes, with MC1R and MC4R particularly relevant at therapeutic concentrations. MC4 receptors occur in numerous areas of the central nervous system.

That means PT-141 is fundamentally different from medications such as sildenafil. It is not simply a vasodilator designed to increase genital blood flow. This central nervous system mechanism is one reason researchers have investigated effects involving desire as well as physical sexual response.