Zafgen said today that a second patient has died in a Phase III trial assessing its lead drug candidate beloranib in people with Prader-Willi syndrome (PWS).
The patient—who received beloranib as part of the study’s open label extension portion—died after being diagnosed with bilateral pulmonary emboli, the company said. The death occurred in Zafgen’s ongoing Beloranib Efficacy Safety and Tolerability in Prader-Willi syndrome (bestPWS), also known as ZAF-311.
Zafgen said it learned of the death yesterday.
“Patient safety remains our top priority and we are investigating the circumstances around this event. We are also engaging in discussions with the FDA while we determine the next steps with the beloranib program,” Zafgen CEO Thomas E. Hughes, Ph.D., said in a statement. “Our thoughts are with the patient and their family at this time.”
The FDA placed beloranib on partial clinical hold in October following the death of the first patient during ZAF-311. That patient’s cause of death, as identified on the death certificate, was determined to be respiratory failure due to pulmonary emboli, Zafgen said on October 22, adding: “It is not known if this event was related to treatment with beloranib.”
At the time the partial clinical hold began, the FDA cited previously reported thromboembolic events in ongoing and prior clinical trials of beloranib, and the fact the nature of the death had not been known at the time.
The partial clinical hold affects ongoing or planned clinical trials, including ZAF-311 and ZAF-312. ZAF-311 is nearly complete.
Zafgen added that it continues expecting to generate top-line results from the randomized portion of ZAF-311 in the first quarter of 2016.
Shares of Zafgen fell 58%, to $6.67 per share as of 9:26 am in premarket trading. Zafgen shares closed at $15.93 yesterday.
Beloranib is a first-in-class methionine aminopeptidase 2 (MetAP2) inhibitor being developed as a twice-weekly injection drug for multiple indications. These include severe obesity in PWS and obesity caused by hypothalamic injury, including craniopharyngioma-associated obesity, and severe obesity in the general population.
Zafgen holds exclusive worldwide rights except in South Korea for the development and commercialization of beloranib. Zafgen has exclusively licensed beloranib from Chong Kun Dang Pharmaceutical Corporation (CKD Pharma) of South Korea.
