General Information

Vyleesi (bremelanotide injection) is a melanocortin receptor agonist. The mechanism by which it improves sexual desire and related distress is unknown.

Vyleesi is specifically indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as 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 with the relationship, or

The effects of a medication or drug substance.

Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation or partner.

Vyleesi is supplied as a solution for subcutaneous injection. The recommended dosage of Vyleesi is 1.75 mg administered subcutaneously in the abdomen or thigh, as needed, at least 45 minutes before anticipated sexual activity. The duration of efficacy after each dose is unknown and the optimal window for Vyleesi administration has not been fully characterized. Patients may decide the optimal time for Vyleesi administration based on how they experience the duration of effect on desire and any adverse reactions such as nausea. Patients should not administer more than one dose within 24 hours. The efficacy of consecutive doses within 24 hours has not been established and administering doses close together may increase the risk of additive effects on blood pressure. Administering more than 8 doses per month is not recommended. Few patients in the phase 3 program received more than 8 doses per month. Also, more frequent dosing increases the risk for focal hyperpigmentation and the length of time per month when blood pressure is increased.

Mechanism of Action

Vyleesi (bremelanotide) is a melanocortin receptor (MCR) agonist that non-selectively activates several receptor subtypes with the following order of potency: MC1R, MC4R, MC3R, MC5R, MC2R. At therapeutic dose levels, binding to MC1R and MC4R is most relevant. Neurons expressing MC4R are present in many areas of the central nervous system (CNS). The mechanism by which VYLEESI improves HSDD in women is unknown. The MC1R is expressed on melanocytes; binding at this receptor leads to melanin expression and increased pigmentation.

Clinical Trial Results

The FDA approval of Vyleesi was based on two 24-week, randomized, double-blind, placebo-controlled trials in 1,247 premenopausal women with acquired, generalized HSDD. Most patients used Vyleesi two or three times per month and no more than once a week. In these trials, about 25% of patients treated with Vyleesi had an increase of 1.2 or more in their sexual desire score (scored on a range of 1.2 to 6.0, with higher scores indicating greater sexual desire) compared to about 17% of those who took placebo. Additionally, about 35% of the patients treated with Vyleesi had a decrease of one or more in their distress score (scored on a range of zero to four, with higher scores indicating greater distress from low sexual desire) compared to about 31% of those who took placebo. There was no difference between treatment groups in the change from the start of the study to end of the study in the number of satisfying sexual events. Vyleesi does not enhance sexual performance.