Zafgen Plagued By More Bad News as Second Patient Dies in Obesity Drug Trial
December 2, 2015
By Mark Terry, BioSpace.com Breaking News Staff
Boston-based Zafgen, Inc. announced today that it was informed yesterday that a second patient had died that was taking part in its pivotal Phase III trial of ZAF-311 (beloranib) for Prader-Willi Syndrome (PWS).
On Oct. 14, 2015, the company announced that a patient had died during its Phase III study. The U.S. Food and Drug Administration (FDA) briefly halted the trial pending further investigation. However, on Oct. 22, Zafgen announced that its Phase IIb and Phase III trials would continue.
It was determined that the cause of death in the first patient was “respiratory failure due to pulmonary emboli. However, it is not known if this event was related to treatment with beloranib,” it was reported in October.
Prader-Willi Syndrome is a rare genetic disorder which is the result of a chromosomal deletion on chromosome 15. Its most prominent symptom is insatiable appetite that leads to excessive eating and obesity. It also includes cognitive disabilities, behavioral problems, short stature, low muscle tone and incomplete sexual development.
Patients with PWS are at higher risk of morbidity and mortality, with an approximate death rate of three percent per year compared to one percent per year for the general population. Childhood mortality in patients with PWS is usually related to respiratory infection and high temperature. In adults with PWS, it is typically associated with circulatory or respiratory problems, as well as other health conditions related to severe obesity.
Beloranib is a first-in-class injectable small molecule compound that reduces hunger while simultaneously stimulating fat metabolism. It inhibits MetAP2, which plays a significant role in controlling metabolism.
The second patient to die in the study received beloranib as part of the open label extension (OLE) part of the Phase III trial. He was diagnosed with bilateral emboli, basically blood clots in the lung.
At least six patients in the trial have also experienced blood clots, although at this time the clotting and deaths have not been directly correlated to beloranib. The first patient who died in October reportedly was 22 years old with a body-mass index (BMI) of 55. Individuals with a BMI of 30 or above are considered obese.
Zafgen , not surprisingly, took a hit at the news and has been struggling since October. Shares traded on March 19 for a high of $51.34, and drifted to a mid-year low of $29.25 on May 20. Shares rose to $46.23 on Sept. 18, but plunged to $10.36 on Oct. 16, two days after news of the first death broke. Shares recovered a little bit to $17.69 on Nov. 27, but are currently trading for $15.93.
In addition to beloranib, Zafgen is developed ZGN-830, a liver-targeted MetAP2 inhibitor, for the treatment of abdominal obesity and nonalcoholic steatohepatitis (NASH), as well as other second-generation MetAP2 inhibitors.
Zafgen indicates it is discussing how to proceed with the FDA, and expects it will have final data presented from the trial early in 2016.
“Our thoughts are with the patient and their family at this time,” said Thomas Hughes, Zafgen’s chief executive officer, in a statement. “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.”