Zafgen has announced the death of a second participant in a Phase III clinical trial of its obesity drug beloranib in patients with the rare genetic disorder Prader-Willi syndrome (PWS).
The company learned of the patient’s death yesterday in the open label extension (OLE) portion of the pivotal Phase 3 ZAF-311 PWS clinical trial.
Zafgen shares plummeted by as much as 63% on Wednesday with uncertainty over the future of its lead candidate.
The second fatality follows the randomised part of the trial’s suspension by the FDA in October after the previous death. The US regulator at the time cited reports of blood clotting in trials as the reason for placing the trial- which is still under investigation- on hold.
The Boston-based company- which specialises in treatments for obesity and complex metabolic disorders- says the second patient died as a result of an arterial blockage in the lung, and that it would work with the FDA to determine a path forward.
“Our thoughts are with the patient and their family at this time,” says Thomas Hughes, chief executive of Zafgen. “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.”
Beloranib is a novel, first-in-class injectable small molecule therapy with a unique mechanism of action that reduces hunger while stimulating the use of stored fat as an energy source. The compound is a potent inhibitor of MetAP2, an enzyme that modulates the activity of key cellular processes that control metabolism.
PWS is the most common known genetic cause of life-threatening obesity, and results in constant hunger that drives patients with PWS to engage in problematic hunger-related behaviours and to gain excessive weight: often leading to morbid obesity and significant mortality. There is currently no cure for the disease.
Zafgen said it still expects top-line results of the randomised portion of the ZAF-311 clinical trial in the first quarter of 2016.