Bremelanotide for Female Sexual Dysfunction
Palatin Technologies is developing bremelanotide as a subcutaneous product intended for female sexual dysfunction (FSD). In a recently completed Phase 2B clinical trial, bremelanotide 1.25 mg and 1.75 mg doses significantly increased sexual arousal, sexual desire and the number of sexually satisfying events, and decreased associated distress in premenopausal women with FSD. Efficacy was seen in both women with hypoactive sexual desire disorder (HSDD) and combined HSDD/female sexual arousal disorder (FSAD).
Bremelanotide, which is a melanocortin agonist (a compound which binds to a cell receptor and triggers a response) drug candidate, is a synthetic peptide analog of the naturally occurring hormone alpha-MSH (melanocyte-stimulating hormone).
In the Phase 2B trial, bremelanotide showed a statistically significant increase in the number of satisfying sexual events (SSEs) versus placebo (mean increase in SSEs of 0.8 (2.9) for 1.75 mg (p = 0.0215) and 0.7 (2.4) for 1.25/1.75 mg pooled (p = 0.0180) versus 0.2 (2.3) for placebo).
Statistically significant or clinically significant trends versus placebo also were seen in the HSDD and HSDD/FSAD groups:
- The mean change in Female Sexual Function Index (FSFI) total score, which measures overall sexual functioning, was 4.4 for 1.75 mg (p = 0.0021) and 3.6 for 1.25 mg and 1.75 mg pooled, versus 1.88 for placebo.
- Mean change in Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) total score, or a measure of distress related to sexual dysfunction, was -13.1 for 1.75 mg (p = 0.0005) and -11.1 for 1.25 mg and 1.75 mg pooled, versus -6.8 for placebo.
Additional analyses on the arousal and desire measurement sub-parts of the FSFI and FSDS-DAO questionnaires and also the sub-populations of patients with HSDD and HSDD/FSAD were consistent with the positive primary analyses.
FSD is a multifactorial condition that has anatomical, physiological, medical, psychological and social components. FSD includes four disorders, hypoactive sexual desire disorder, female sexual arousal disorder, sexual pain disorder and orgasmic disorder. To establish a diagnosis of FSD, these syndromes must be associated with personal distress, as determined by the affected women. Approximately 40 million American women are affected by FSD. The National Health and Social Life Survey, a probability sample study of sexual behavior in a demographically representative cohort of United States adults ages 18 to 59, found that approximately 43% of women suffer from some form of FSD. There are no Food and Drug Administration approved drugs for FSD.
Bremelanotide was well-tolerated during the trial. The most common types of treatment-emergent adverse events reported more frequently in the bremelanotide arms were facial flushing, nausea and emesis, which were mainly mild-to-moderate in severity. The study dosed 394 patients. A total of 26 patients discontinued based on predefined blood pressure criteria; these patients were evenly distributed across the placebo and bremelanotide dosing arms. An additional 12 patients discontinued from the study due to adverse events (placebo 2, bremelanotide 10). Adverse events that most commonly led to discontinuation were nausea and emesis. No serious adverse events were attributed to bremelanotide during the trial.
Based on discussions with the FDA at an upcoming end-of-Phase 2B meeting, including agreement with FDA on the final Phase 3 protocol design, Palatin Technologies anticipates Phase 3 clinical trials could start in the fourth-quarter of 2013.
We extensively studied bremelanotide for sexual dysfunction in nasal formulations, administered as a single spray in one nostril. Increases in blood pressure were observed in some patients receiving nasally administered bremelanotide, and this observed increase was a significant factor leading us to discontinue work on nasally administered bremelanotide as a first-line therapy for sexual dysfunction. We believe that with subcutaneous administration exposure to bremelanotide is tightly controlled, limiting exposures to levels associated with increases in blood pressure and other adverse events.
Palatin Technologies has extensive clinical experience with bremelanotide. Over 2,000 patients have received bremelanotide in 30 clinical studies with either intranasal or subcutaneous formulations, with demonstrated efficacy for both FSD and erectile dysfunction.