Female Hormonal Deficiencies/Abnormalities

February 8, 2016

Zafgen issued results of a pivotal, double-blind, placebo-controlled, phase III trial evaluating the safety and efficacy of beloranib for Prader-Willi syndrome (PWS). The bestPWS ZAF-311 study randomized 107 patients to receive twice-weekly subcutaneous injections of either 2.4mg or 1.8mg of beloranib or placebo. Seventy-four patients completed the full 26 weeks of treatment per the trial protocol, and 27 patients completed at least 75% of the randomized treatment period prior to the suspension of dosing in the trial in October 2015. There were six patients who discontinued early. The co-primary efficacy endpoints for this trial were improvement in hyperphagia-related behaviors and reduction in body weight. Patients in the trial were on average 20 years old, had an average BMI of 40kg/m2 and an average hyperphagia total score of 16.9, consistent with moderate to severe hyperphagia, at the beginning of randomized treatment. Treatment with the 2.4mg and the 1.8mg doses of beloranib resulted in reductions of hyperphagia-related behaviors of 7 units (p=0.0001) and 6.3 units (p=0.0003) relative to placebo, respectively, as measured by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Patients randomized to receive placebo displayed substantial (4.15%) gain in body weight over the course of the six months of randomized treatment. Patients treated with beloranib, in contrast to placebo, lost weight, with the 2.4mg dose arm displaying a 5.3% reduction from baseline, with a placebo-adjusted weight loss of 9.45%. In December 2015, the FDA placed the beloranib IND application on complete clinical hold due to an imbalance in severe venous thromboembolic events, including two patient deaths. Zafgen plans to present to the FDA the efficacy and safety data from the bestPWS ZAF-311 study, data from the phase IIb trial of beloranib in severe obesity complicated by type 2 diabetes and a proposal for a risk mitigation strategy for beloranib in PWS.

October 22, 2007

Palatin issued positive results from a phase II trial of bremelanotide for the treatment of female sexual arousal disorder. This double-blinded, placebo-controlled trial enrolled 163 pre- and postmenopausal women. The subjects were followed for one month to determine their baseline level of sexual dysfunction and were then randomized to receive intranasal doses of either placebo or bremelanotide (10 mg). The subjects were assessed over a two month period for changes in sexual function using the Female Sexual Encounter Profile (FSEP), the Female Sexual Function Index (FSFI) and the Female Sexual Distress Score (FSDS). The postmenopausal women showed statistically significant improvements in the endpoints when compared to baseline and placebo, and overall satisfaction at one and two months. The pre-menopausal women treated with bremelanotide showed statistically significant improvements in the endpoints when compared to baseline and overall satisfaction at one and two months. However, while a positive trend toward improvement was seen in this group when compared to placebo, the differences were not statistically significant. Based on the results, Palatin plans to move forward with the development of bremelanotide.