New data from phase III bestPWS ZAF-311 study of ZGN 433 (beloranib) shows safety and efficacy in Prader-Willi syndrome- Zafgen

Zafgen announced new data from the bestPWS ZAF-311 study, a pivotal, double-blind, placebo-controlled Phase III trial evaluating the safety and efficacy of ZGN 433 (beloranib) in patients with Prader-Willi syndrome (PWS) during the six-month randomized treatment period. Data presented during ENDO 2016 showed that beloranib was associated with improvement in total cholesterol, LDL cholesterol and other cardiometabolic risk factors, and a reduction in fat mass when compared to placebo.

As previously reported, the bestPWS study achieved its co-primary efficacy endpoints, as beloranib demonstrated a statistically significant reduction in both body weight and hyperphagia-related behaviors, making it the first investigational drug to demonstrate a positive impact on these two hallmark challenges of PWS.

In the bestPWS ZAF-311 study, 107 patients were randomized to receive twice-weekly subcutaneous injections of either 2.4 mg or 1.8 mg of beloranib or placebo. Seventy-four patients completed the full 26 weeks of treatment per the study protocol, and 27 patients completed at least 75 percent of the randomized treatment period prior to the suspension of dosing in the trial in October 2015. Patients randomized to receive placebo displayed substantial (4.15%) increase in body weight over the course of the six months of randomized treatment. Body weight gain in this patient population was anticipated, and typically occurs throughout life generally due to a lack of effective treatments for managing obesity. Patients treated with beloranib experienced a reduction in weight, with the 2.4 mg dose arm displaying a 5.3 percent reduction from baseline, with a placebo-adjusted weight loss of 9.45 percent. The co-primary efficacy endpoints for this trial were improvement in hyperphagia-related behaviors and reduction in body weight. Secondary endpoints in this trial included improvement in total body fat mass and improvement in lipids and markers of cardiometabolic risk (TC and LDL). Patients treated with beloranib demonstrated a significant reduction in total body mass and fat mass at both the 1.8 mg and 2.4 mg doses of beloranib. Lean body mass was minimally changed from baseline with a 0.5 kg loss in the 1.8 mg beloranib arm, a 0.7 kg loss in the 2.4 mg beloranib arm and an increase of 0.7 kg in the placebo arm. Approximately 90 percent of loss in total body mass with beloranib was due to loss of body fat, indicating preferential loss of fat with minimal change in lean mass. The most common adverse events in this study were injection site bruising, aggression, and hyperphagia, generally of mild severity and transient in nature.