PT-141 HA - 10MG

PT-141 (bremelanotide) is a synthetic melanocortin receptor agonist approved for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women.[1][2][3] It is administered as a subcutaneous injection (1.75 mg) on an as-needed basis, approximately 45 minutes prior to anticipated sexual activity, with a maximum of one dose per 24 hours and no more than eight doses per month.[1][3] Bremelanotide is not indicated for use in postmenopausal women or men, and should be discontinued after 8 weeks if no clinical benefit is observed.[1][3]

Mechanism of Action:

Bremelanotide is a nonselective melanocortin receptor agonist, with highest affinity for MC4R, which is expressed in the hypothalamus and is implicated in sexual desire and arousal pathways.[2][4] Activation of MC4R increases central dopamine release, modulating excitatory pathways involved in sexual response.[4]

Efficacy:

Phase 3 randomized, double-blind, placebo-controlled trials (RECONNECT studies) demonstrated statistically significant improvements in sexual desire (FSFI-desire domain) and reductions in distress related to low sexual desire (FSDS-DAO item 13) compared to placebo.[5][6][3] The clinical benefit is modest, with mean increases in desire domain scores of 0.30–0.42 and reductions in distress scores of -0.29 to -0.37.[5][6][3] Efficacy is consistent across age, BMI, and hormonal contraceptive use subgroups.[6] Long-term open-label extension studies confirm sustained improvements in HSDD symptoms without new safety signals.[7]

Safety and Adverse Effects:

The most common adverse events are nausea (up to 40%), flushing (20%), headache (11–12%), and injection site reactions (5%).[1][5][8][9][7][3] Nausea is the leading cause of discontinuation (18%).[8][3] Focal hyperpigmentation may occur, especially with frequent dosing beyond label recommendations.[8][3] Transient increases in blood pressure and reductions in heart rate have been observed; bremelanotide should be used with caution in patients at risk for cardiovascular disease and is contraindicated in uncontrolled hypertension or known cardiovascular disease.[8][3] Most adverse events are mild to moderate and resolve spontaneously.[8][9][7][3] Drug-drug interactions are minimal, with no clinically significant interactions with ethanol.[1][10]

Clinical Considerations:

Bremelanotide is self-administered via autoinjector and is intended for on-demand use. It should not be used more than once in 24 hours or more than eight times per month.[1][3] Blood pressure should be well controlled prior to initiation, and patients should be counseled regarding the risk of nausea and possible skin hyperpigmentation.[8][3] Discontinue if no benefit after 8 weeks.[1][3]

Summary:

PT-141 (bremelanotide) is a first-in-class melanocortin receptor agonist for acquired, generalized HSDD in premenopausal women, with modest efficacy and a well-characterized safety profile. The most common adverse events are nausea, flushing, headache, and injection site reactions; cardiovascular monitoring is recommended in at-risk populations.[1][5][8][2][9][6][7][3][11][10][4]

References

1. Bremelanotide: New Drug Approved for Treating Hypoactive Sexual Desire Disorder. Mayer D, Lynch SE. The Annals of Pharmacotherapy. 2020;54(7):684-690. doi:10.1177/1060028019899152.
2. Bremelanotide: First Approval. Dhillon S, Keam SJ. Drugs. 2019;79(14):1599-1606. doi:10.1007/s40265-019-01187-w.
3. Vyleesi. Food and Drug Administration. Updated date: 2025-01-10.
4. The Neurobiology of Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder in Premenopausal Women. Pfaus JG, Sadiq A, Spana C, Clayton AH. CNS Spectrums. 2022;27(3):281-289. doi:10.1017/S109285292100002X.
5. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Kingsberg SA, Clayton AH, Portman D, et al. Obstetrics and Gynecology. 2019;134(5):899-908. doi:10.1097/AOG.0000000000003500.
6. Prespecified and Integrated Subgroup Analyses From the RECONNECT Phase 3 Studies of Bremelanotide. Simon JA, Kingsberg SA, Portman D, et al. Journal of Women's Health (2002). 2022;31(3):391-400. doi:10.1089/jwh.2021.0225.
7. Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder. Simon JA, Kingsberg SA, Portman D, et al. Obstetrics and Gynecology. 2019;134(5):909-917. doi:10.1097/AOG.0000000000003514.
8. Safety Profile of Bremelanotide Across the Clinical Development Program. Clayton AH, Kingsberg SA, Portman D, et al. Journal of Women's Health (2002). 2022;31(2):171-182. doi:10.1089/jwh.2021.0191.
9. An Evaluation of Bremelanotide Injection for the Treatment of Hypoactive Sexual Desire Disorder. Cipriani S, Alfaroli C, Maseroli E, Vignozzi L. Expert Opinion on Pharmacotherapy. 2023;24(1):15-21. doi:10.1080/14656566.2022.2132144.
10. Phase I Randomized Placebo-Controlled, Double-Blind Study of the Safety and Tolerability of Bremelanotide Coadministered With Ethanol in Healthy Male and Female Participants. Clayton AH, Lucas J, DeRogatis LR, Jordan R. Clinical Therapeutics. 2017;39(3):514-526.e14. doi:10.1016/j.clinthera.2017.01.018.
11. Melanocortins in the Treatment of Male and Female Sexual Dysfunction. Shadiack AM, Sharma SD, Earle DC, Spana C, Hallam TJ. Current Topics in Medicinal Chemistry. 2007;7(11):1137-44. doi:10.2174/156802607780906681.