FDA suspends clinical development of obesity drug after second US trial death
In October, a patient recruited for a Phase III trial investigating Zafgen’s small molecule candidate beloranib died from what CEO Thomas Hughes said last month was “determined to be driven by a thromboembolic event.”
This led to the US Food and Drug Administration (FDA) placing the candidate on partial clinical hold, but a second patient death on Tuesday from pulmonary embolism has led to a complete suspension of all clinical work.
The ZAF-311 trial involved 108 obese subjects with Prader-Willi Syndrome (PWS) - a rare genetic disorder with a high rate of mortality linked to obesity - being studied across a number of US sites. Both deaths occurred in patients who had taken beloranib, the firm has said.
A spokesperson from the firm was unable to comment on the trial sites involved, "given that this is an ongoing issue," and would not divulge which contract research organisation (CRO) was carrying out the study.
But Hughes said in a statement yesterday: “We are working diligently to assemble and analyse the data from our ZAF-311 clinical trial to be able to provide a clear view of the safety and efficacy of beloranib in the PWS population."
He added: “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’s share price plummeted Wednesday morning to its lowest level since the firm went public in June 2014.
Beloranib is an injectable small molecule which inhibits MetAP2, an enzyme which helps modulate cellular processes that control metabolism, reducing the tone of signals that drive lipid synthesis by the liver and fat storage throughout the body.
Zafgen licensed the technology from Korean firm Chong Kun Dang Pharmaceutical Corporation, and holds the worldwide rights, outside Korea.
Beloranib related?
During a call discussing results in November (transcript here), Hughes said the first death was due to “respiratory failure as a consequence of a pulmonary embolus,” and added the firm had seen a further six events of “varying severity” related to thromboembolic events in patients who had taken beloranib across three trials.
He continued: “It’s hard at this time to say whether these events are related to beloranib exposure or a function of events that would have otherwise occurred in the absence of drug treatment,” and thromboembolic causes of death are not uncommon among such patient populations.
“Patients with PWS are on average morbidly obese and suffer from a range of developmental issues and have a variety of health issues that leads to early death.”
