Vyleesi History and Development: How Bremelanotide Went From Sunscreen Peptide to FDA-Approved HSDD Treatment

Did bremelanotide really start as a tanning peptide?

Partly, and the familiar version of the story folds two different molecules into one.

The melanocortin program produced two clinical candidates. Melanotan I, a linear peptide, was patented and tested for tanning of the skin, on the idea that a therapeutic tan might lower the risk of skin cancer. Melanotan II, a cyclic truncated peptide, was patented and tested for the diagnosis and treatment of male erectile dysfunction [1]. Bremelanotide comes from the second branch: a 2006 review by Hadley and Dorr describes PT-141 as a new melanotan II analog from Palatin Technologies that had initial phase I/II trials and was scheduled to enter pivotal phase III testing [1].

So the tanning link is real but indirect. The documented tanning work involved melanotan I; PT-141 was developed from melanotan II, which was studied for male erectile dysfunction [1]. That review describes melanotan II as an erectile-dysfunction candidate, and assigns the tanning work to melanotan I [1].

What the early laboratory work showed

PT-141 is a synthetic peptide analog of alpha-MSH and an agonist at MC3R and MC4R, receptors expressed mainly in the central nervous system [6]. In rats and nonhuman primates it produced penile erections, and in rats it increased c-Fos immunoreactivity in hypothalamic neurons, a marker of neuronal activation [6]. In studies of men with and without erectile dysfunction, PT-141 produced a rapid, dose-dependent increase in erectile activity [6].

The female data came from a separate experiment. In a 2004 study in rats, PT-141 selectively increased solicitational behaviors, the appetitive approach side of sexual behavior, without changing lordosis, pacing or other sexual behaviors and without causing generalized motor activation [7]. The authors wrote that PT-141 may be the first identified pharmacological agent with the capability to treat female sexual desire disorders [7]. A 2009 review of sexual desire pathways describes hypothalamic and mesolimbic dopamine systems as the core of the excitatory system, a system that also includes melanocortins and oxytocin [8].

The current label describes bremelanotide as a nonselective melanocortin receptor agonist with a potency order of MC1R, MC4R, MC3R, MC5R and MC2R, and states that binding at MC1R and MC4R is most relevant at therapeutic doses [2]. The early papers describe it as an MC3R and MC4R agonist [6]. The label also says plainly that how the drug improves HSDD is unknown [2].

An early study in women used a nasal spray

In a 2006 double-blind crossover trial, 18 premenopausal women with female sexual arousal disorder received a single 20 mg intranasal dose of bremelanotide or matching placebo [5]. More women reported moderate or high sexual desire after bremelanotide than after placebo (P=0.0114). The difference in feelings of genital arousal was a trend (P=0.0833), and among women who attempted intercourse within 24 hours, significantly more were satisfied with their level of arousal after bremelanotide (P=0.0256) [5]. Vaginal vasocongestion measured by photoplethysmography did not change significantly [5].

That is one small, single-dose study in women with a different diagnosis (arousal disorder, not HSDD), and it tested one dose rather than a course of treatment [5]. The nasal route also appears in the label's pharmacology section, where a 20 mg intranasal dose is noted to produce a mean Cmax 2.5-fold higher than Vyleesi's [2]. The approved product is not intranasal.

Reformulation as a subcutaneous injection

The approved form is a prefilled autoinjector that delivers 1.75 mg subcutaneously into the abdomen or thigh, as needed, at least 45 minutes before anticipated sexual activity; the label says not to use more than one dose in 24 hours and does not recommend more than eight doses per month [2]. After a 1.75 mg dose, median Tmax is about 1.0 hour, absolute bioavailability is about 100%, and mean terminal half-life is about 2.7 hours [2].

The RECONNECT trials

Two identical phase 3 trials, RECONNECT 301 and 302 (NCT02333071 and NCT02338960), randomized 1,267 premenopausal women with HSDD 1:1 to bremelanotide 1.75 mg or placebo for 24 weeks [4]. The safety population was 1,247 and the modified intent-to-treat population 1,202; mean age was 39 [4].

On the coprimary endpoints, bremelanotide increased FSFI-desire domain scores by 0.30 points in study 301 and 0.42 in study 302 versus placebo (integrated 0.35; all P<0.001), and reduced the FSDS-DAO item 13 distress score by 0.37, 0.29 and 0.33 points (P<0.001, P=0.005 and P<0.001) [4]. The label reports FSFI-desire changes of 0.5 versus 0.2 in study 1 and 0.6 versus 0.2 in study 2 [2]. The trials found no significant difference between groups in the number of satisfying sexual events [4].

Discontinuation was common and uneven: 40% versus 13% in study 1 and 39% versus 25% in study 2 [2]. Nausea was reported by 40.0% of Vyleesi patients versus 1.3% on placebo; 13% used an anti-nausea medicine and 8% stopped the trials because of it [2]. Nausea was highest after the first dose, reported by 21% of patients, and fell to about 3% with later doses [2]. Flushing occurred in 20.3% versus 0.3%, headache in 11.3% versus 1.9%, and injection site reactions in 13.2% versus 8.4% [2].

Each dose transiently raises blood pressure and lowers heart rate [2]. In the trials the maximal increases were 6 mmHg systolic and 3 mmHg diastolic, peaking 2 to 4 hours after dosing, with a heart rate reduction of up to 5 beats per minute; values usually returned to baseline within 12 hours [2]. In the 52-week open-label extension, 684 women enrolled and 272 completed; the most common drug-related events were nausea at 40.4%, flushing at 20.6% and headache at 12.0%, and the analysis was descriptive with no placebo group [9].

One further trial came after approval: a phase 4 single-dose study in 228 healthy women found that taking oral ondansetron 30 minutes before Vyleesi did not reduce nausea, so the label does not recommend it [2].

FDA approval and what the label covers

The FDA approved bremelanotide as Vyleesi on June 21, 2019 under NDA 210557. The application was originally held by AMAG and is now held by Cosette Pharmaceuticals [2][3]. The approved indication is premenopausal women with acquired, generalized HSDD, meaning low sexual desire causing marked distress or interpersonal difficulty that is not due to a coexisting medical or psychiatric condition, relationship problems, or a medication or drug [2]. The label states that Vyleesi is not indicated for HSDD in postmenopausal women or in men, and not to enhance sexual performance [2].

Vyleesi has no boxed warning, and no risk evaluation and mitigation strategy appears in the label or in the 2019 approval letter [2][3]. The label lists uncontrolled hypertension or known cardiovascular disease as contraindications and says Vyleesi is not recommended for patients at high risk of cardiovascular disease [2].

On October 22, 2026 the FDA approved a labeling supplement (S-005) updating Section 8, Use in Specific Populations, and the patient information; that text was not yet in the DailyMed version of the label on October 28, 2026 [2][10].

What the name PT-141 means now

PT-141 was the compound's development name; Vyleesi is the FDA-approved bremelanotide product [1][2]. 'PT-141' products sold as compounded or research-use peptides are not Vyleesi and are not FDA-approved drugs; compounded drugs are not reviewed by the FDA for safety, effectiveness or quality before marketing [11].

Bremelanotide does not appear on the FDA's list of bulk drug substances that may present significant safety risks when compounded [12]. It is also not named on WADA's 2026 Prohibited List [13].