HOLLYWOOD, FLA. – Subcutaneous bremelanotide self-administered at home by premenopausal women with sexual dysfunction significantly boosted sexual arousal and desire and their number of satisfying sexual events, based on data from a phase IIb clinical trial.
The novel therapy proved effective both in women with hypoactive sexual desire disorder and in those with combined hypoactive sexual desire disorder/female sexual arousal disorder, among the most common forms of female sexual dysfunction, Dr. Anita H. Clayton noted at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.
Female sexual dysfunction is distressing, very common, and multifactorial, and there is at present no approved pharmacotherapy for these disorders, according to Dr. Clayton, professor of psychiatry and neurobehavioral sciences at the University of Virginia, Charlottesville. Thus, this represents an area of significant unmet medical need, she said.
Bremelanotide is a cyclic 7-amino-acid melanocortin peptide. It is a synthetic analog of the hormone alpha-melanocyte–stimulating hormone (alpha-MSH). It functions as a melanocortin-4 receptor agonist. Bremelanotide, like alpha-MSH, is thought to modulate brain pathways involved in sexual response, Dr. Clayton explained.
She reported data from a phase IIb randomized, double-blind, multicenter trial involving 327 women who met diagnostic criteria for hypoactive sexual desire disorder or combined hypoactive sexual desire disorder/female sexual arousal disorder. After receiving instruction in self-administration of subcutaneous injections, all participants underwent 4 weeks of single-blind placebo self-dosing at home on an as-needed basis. Then they were randomized to 12 weeks of double-blind home treatment with placebo or bremelanotide at 0.75 mg, 1.25 mg, or 1.75 mg in prefilled syringes. Participants were instructed to inject themselves approximately 45 minutes prior to sexual activity. They were not to exceed 1 dose per day, or 16 doses in a 4-week period.
The primary endpoint was change between the numbers of satisfying sexual events during the 28-day baseline period on placebo and during the final 28 days of the 12-week double-blind study period, using the Female Sexual Encounter Profile-Revised
The mean increase was 0.2 events in placebo-treated controls. Women randomized to 0.75 of bremelanotide didn’t fare significantly better than that.
However, women using bremelanotide at 1.25 mg had a mean 0.7-event increase from baseline, and those on 1.75 mg averaged a 0.8-event increase, both of which were significantly better than placebo.
Secondary endpoints were also positive, in dose-dependent fashion. The mean change over time in the Female Sexual Function Index total score, a validated measure of overall sexual functioning, was 1.88 for placebo, 3.6 in the pooled analysis of patients on bremelanotide at 1.25 or 1.75 mg, and 4.4 in those on 1.75 mg.
Similarly, the mean improvement on the FSDS-DAO (Female Sexual Distress Scale-Desire/Arousal/Orgasm) total score, an indicator of sexual dysfunction–related distress, was –6.8 for placebo, –11.1 for the pooled group on 1.25 or 1.75 mg of bremelanotide, and –13.1 for women on 1.75 mg.
These are clinically meaningful improvements, according to Dr. Clayton. Of note, the mean total score improvements, compared with baseline on these outcome measures, were still growing during the third and final month of double-blind treatment.
Also encouraging was the large percentage of women on bremelanotide whose scores reached thresholds indicative of normal levels of sexual function, she continued. For example, a Female Sexual Function Index total score greater than 26.5 was achieved in 42.7% of women on bremelanotide at 0.75 mg, 45.5% of those on 1.25 mg, and 49% on 1.75 mg, compared with 36.5% of placebo-treated controls. Moreover, a FSDS-DAO total score less than 18 was attained by 28.5% of women on placebo, 40.5% of those on bremelanotide at 0.75 mg, 45.6% on 1.25 mg, and 47.5% of those on 1.75 mg.
The drug therapy was safe and generally well tolerated. The most common bremelanotide-associated side effects were nausea, facial flushing, and headache, which affected 9%-24% of patients in dose-dependent fashion and were typically mild to moderate in nature.
Bremelanotide-treated patients averaged an increase in blood pressure of approximately 2 mm Hg, largely restricted to the first 4 hours after dosing. The number of patients forced to withdraw from the study based on predefined blood pressure change criteria was evenly distributed among the placebo and treatment groups, which was reassuring, Dr. Clayton said. Approximately 5 years ago, development of an intranasal formulation of bremelanotide for treatment of male erectile dysfunction as well as female sexual dysfunction was discontinued because of concerns about significant drug-induced hypertension. The current study, as well as other data, indicates that hypertension isn’t an issue with subcutaneous administration, she noted.