Memorandum
Zafgen recently announced positive topline data from a phase 1b trial of second-generation MetAP2 inhibitor ZGN-1061. The company now plans to initiate a phase 2 trial in 2H17, investigating the agent in people with type 2 diabetes and overweight/obesity – this matches timing outlined in Zafgen’s 4Q16 earnings update. The phase 1 trial featured a single ascending dose phase (n=39 healthy volunteers) followed by a multiple ascending dose phase (n=29 patients with overweight/obesity), and both segments compared the MetAP2 inhibitor vs. placebo. ZGN-1061, dosed twice-weekly over 28 days, was safe and well-tolerated. Participants randomized to the active agent lost an average of one pound per week, which is promising early evidence for weight loss efficacy. Importantly, phase 1 showed no evidence of thrombosis. Zafgen’s flagship product, first-generation MetAP2 inhibitor beloranib, was discontinued after two thrombosis-related deaths in phase 3 trials, so it will be absolutely critical for the company to provide compelling, reassuring safety data on this front throughout clinical development of second-gen ZGN-1061. We’re glad to see Zafgen’s continued commitment to obesity as a therapeutic area, despite the disappointing termination of beloranib and despite the challenging commercial landscape for weight loss drugs. Reluctance to consider pharmacotherapy persists among providers who treat obesity, and safety concerns undoubtedly play a role in this. Many safety issues arose with the first generation of obesity drugs, so we imagine that new products in this class will have to show incredibly convincing safety results to be successful on the market. And we’d love nothing more than to see a spike in uptake of these therapies, considering how the vast majority of obesity goes untreated (according to Novo Nordisk’s recent 1Q17 update, only 2% of 600 million people with obesity worldwide are receiving medical treatment). That said, ZGN-1061 still has a long way to go through clinical development. See our updated competitive landscape of all the obesity therapies in the pipeline for the big picture.
-- by Payal Marathe, Abigail Dove, and Kelly Close