Zafgen ends development of Prader-Willi drug

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Biotech Zafgen has ended development of its beloranib for the rare genetic condition Prader-Willi syndrome (PWS), sending its shares plummeting.

CEO Thomas Hughes said in a letter to patients that the US firm had taken the difficult decision after the US Food and Drug Administration (FDA) put a hold on the phase 3 bestPWS clinical trial in December, following two deaths from pulmonary emboli.

Hughes said the company had been analysing data for the last seven months, taking advice from PWS experts, thrombosis experts and the FDA, and concluded that the drug is inherently unsafe.

There is no clear path for approval in PWS, which has symptoms including learning disabilities and obsessive eating, even in combination with anticoagulants.

Hughes said the company “cannot move forward under these circumstances.”

BestPWS was a phase 3 trial comparing beloranib with placebo, which evaluated safety and its effect on total body fat mass, body weight and food-related behaviours in obese volunteers with PWS.

Zafgen will instead focus resources on another obesity drug – a second generation MetAP2 inhibitor ZGN-1061.

The Boston, Massachusetts-based firm will develop the drug in severe and complicated obesity.

Like beloranib, ZGN-1061 is a fumagillin-class MetAP2 inhibitor. It was discovered by Zafgen’s researchers as part of a multi-year campaign to identify novel compounds avoiding preclinical safety concerns associated with beloranib.

These included teratogenicity and effects on testicular function.

It also has similar efficacy, potency and range of activity in animal models of obesity as beloranib, but a reduced potential to impact thrombosis. Zafgen is screening patients for a phase 1 clinical trial.

Following the news, shares on the NASDAQ stock exchange fell more than 50% to $3.51.

There is no cure for PWS and the best hope for patients are drugs to manage the symptoms, such as a human growth hormone, and a dedicated care plan.