AUA: ED Drug May Boost Psyche and Functional Performance

ANAHEIM, Calif., May 24 -- An investigational centrally active melanocortin agonist gives men with erectile dysfunction a psychological boost as well as a physical one, researchers reported here.

Men who used bremelanotide in an intranasal formulation reported improvement in sexual relationships, sexual satisfaction, confidence, and self-esteem. The synthetic peptide also led to significant improvement in erectile function during 12 weeks of on-demand therapy.

"These results indicate that bremelanotide improves sexual confidence and has the potential to be an important treatment option for patients with erectile dysfunction," said psychologist Stanley Althof, Ph.D., of Case Western Reserve in Cleveland, at the American Urological Association meeting.

Bremelanotide is the first of a new class of erectile dysfunction drugs known as melanocortin receptor agonists. Unlike PDE-5 inhibitors, which have a vascular mechanism of action, bremelanotide exerts its effects through the central nervous system. According to the manufacturer, Palatin Technologies of Cranbury, N.J., the agent binds primarily to melanocortin receptor 4 in the hypothalamus, triggering descending neural signals to the penis.

In a multicenter, randomized, placebo-controlled trial, 726 nondiabetic men with erectile dysfunction were randomized to placebo or to one of five intranasal bremelanotide doses ranging between 5 mg and 15 mg, said Dr. Althof. Patients self-administered therapy as needed, 45 minutes before sexual activity.

The study participants had a mean age of 55 years and a six-year history of erectile dysfunction. The population comprised similar numbers of men with mild, moderate, and severe erectile dysfunction, and most of the men had experience with PDE5 inhibitors.

Sexual function was assessed by means of the International Index of Erectile Function (IIEF) at baseline and at the end of the study. Patients assigned to placebo averaged a one-point improvement in IIEF score over the course of the trial. In contrast, patients assigned to bremelanotide doses of 7.5 mg to 15 mg had four- to five-point improvements in IIEF score (P?0.05 compared with placebo).

As part of the study protocol, participants completed the Self Esteem and Relationship (SEAR) Questionnaire, a 14-item survey instrument that assesses change in two major domains: sexual relationship and confidence, said Dr. Althof. The confidence domain has two sub-domains of self-esteem and overall relationship.

Patients randomized to all but the lowest (5 mg) bremelanotide doses improved by about 15 to 17 points on the sexual relationship domain of SEAR, compared to about a five-point improvement in the placebo group (p?0.01) In general, the bremelanotide groups had greater improvement in the remaining major and minor domains compared to placebo, but the differences were not statistically significant.

Dr. Althof said that SEAR scores improved across all categories of erectile dysfunction severity, although patients with mild or severe ED tended to derive the greatest overall benefit. In addition, IIEF and SEAR domains exhibited statistically significant correlations.

Another bremelanotide study reported here involved 294 men with diabetes and erectile dysfunction. The patients were randomized to placebo or one of three doses of bremelanotide (10, 12.5, or 15 mg) and self-administered treatment as needed for 12 weeks.

Patients assigned to the two highest bremelanotide doses had significantly greater improvement in the erectile function domain of the IIEF compared to placebo (P<0.05), said urologist Christopher Steidle, M.D., of Indiana University in Indianapolis.

In both studies, bremelanotide-treated patients had higher rates of adverse effects compared to placebo, but the effects tended to be mild or moderate in severity. More common adverse events reported by bremelanotide patients included nausea, emesis, flushing, transient increases in blood pressure, headache, spontaneous erection, skin darkening, and nasal symptoms.

Bremelanotide is not a new drug, commented Ira Sharlip, M.D., of the University of California San Francisco, and a spokesperson for the AUA. The agent originally was developed as a skin-tanning product. Thus far, clinical results with the intranasal formulation developed for management of erectile dysfunction have been promising, he said.

"It has a different mechanism of action, so that creates the potential for combination therapy with a PDE5 inhibitor," said Dr. Sharlip. "Right now the manufacturer is evaluating it as monotherapy, but I wouldn't be surprised to see bremelanotide and a PDE5 inhibitor used in combination."