On June 24, 2019, the FDA approved Vyleesi (bremelanotide injection) for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. Bremelanotide is an analogue of the α-melanocyte-stimulating hormone, which activates melanocortin in the nervous system. This hormone was originally explored as a sunless tanning agent in the 1980s. Through an accidental discovery, it was found to cause spontaneous erections after one of the scientists self-administered it. Studies in sexual dysfunction began in the 2000s in both men and women, and though the drug was effective in both genders, it was only pursued for an indication in women (most of the male data is unpublished, so we aren’t sure of its effectiveness there and we are not recommending it in men).

How is it dosed?
Bremelanotide has to be injected because it has low oral bioavailability. It comes as a single-dose, disposable, 0.3 mL auto-injector that contains 1.75 mg of the drug. Patients self-administer 1 dose subcutaneously in the abdomen or thigh, as needed, at least 45 minutes before anticipated sexual activity. Its half-life is 2.7 hours, but effects can last up to 24 hours. Due to concerns about blood pressure elevations and skin pigmentation, patients should not exceed 1 dose in a 24-hour period or more than 8 doses in a month.

How effective is it?
Statistically, this drug makes a difference, but it’s not clear that the difference is meaningful or worth the risk. The overall effect size was small and comparable to that seen with flibanserin (Addyi): 0.3 for bremelanotide vs 0.4 for flibanserin (Pyke RE and Clayton AH, Sex Med Rev 2018;6(3):358–366). Two large, 24-week RCTs earned its FDA approval, but fewer than 60% of patients on the drug completed those trials (n = 1247). There was no difference in the number of sexual events between the treatment and placebo groups, but the average patient improved 0.6 points in sexual desire on the 6-point Female Sexual Function Index (FSFI) questionnaire.

What are the side effects, contraindications, and drug interactions?
The most common side effects are nausea (40%), flushing (20%), injection site reactions (13%), and headaches (11%). Blood pressure rises and heart rate decreases after each dose, so avoid in patients with cardiovascular risks. Focal hyperpigmentation is a rare side effect (1%), with a risk that increases with darker skin and more frequent use. This discoloration is not limited to the injection site and did not resolve after discontinuation in half of the women who experienced it. Unlike flibanserin, there is no interaction with alcohol. Bremelanotide slows gastric emptying, which may reduce absorption of some oral medications, most notably oral naltrexone, antibiotics, and analgesics. Animal studies show fetal harm, so avoid in pregnancy.

What is the cost?
Bremelanotide is sold in 4-dose packs and is only available through online specialty pharmacies that providers can access at www.vyleesipro.com by e-prescription or fax. For patients whose insurance covers bremelanotide, a copay card will lower their cost to $0 for the first 4-pack and $99 for every 4-pack refill. Its manufacturer is planning a benefit program for patients whose insurance does not cover it.

TCPR’s Take: Bremelanotide has some large hurdles to overcome, including cost, self-injection, modest benefits, high rates of nausea, and a rare but potentially permanent side effect of skin discoloration.

Marketing of FHSDD medications has reached new extremes. Take Vyleesi, where the maker hired a telemedicine practice to prescribe it directly through the Vyleesi website. In our Oct­ober 14 podcast, we go undercover to investigate. Search for “Carlat” on your podcast store.