October 22, 2015
By Mark Terry, BioSpace.com Breaking News Staff
Boston-based Zafgen Inc. announced today that its Phase IIb and Phase III clinical trials of belaranib for obesity will continue, despite a recent death in one of the trials.
On Oct. 14, 2015, the company announced that a patient had died during the course of its Phase III study of beloranib in Prader-Willi Syndrome (PWS). The U.S. Food and Drug Administration (FDA) had the trial halted pending further investigation and an evaluation of the patient’s death.
The company indicates that the patient who died recently, based on the death certificate, “has been determined to be respiratory failure due to pulmonary emboli. However, it is not known if this event was related to treatment with beloranib.” Results from an autopsy are still pending.
Consulting with the FDA, Zafgen plans to fully assess the safety and efficacy of the drug and plans to continue the six-month open label extension (OLE) of ZAF-311 clinical trial in PWS in order to acquire the data. It says enough patients have completed the randomized treatment portion of both trials in order to determine the efficacy of the drug and to provide information regarding continuing with future trials. It expects top-line results from both trials in the first quarter of 2016.
“The strategic decision to analyze results from the ZAF-311 and ZAF-203 clinical trials early allows us to better preserve data integrity by limiting dose interruption in both clinical trials, and inform the future development of this important product candidate,” said Dennis Kim, Zafgen’s chief medical officer, in a statement. “PWS is a life-threatening and complex rare disorder that severely impacts the quality of life of both patients and their families, and we continue to believe that beloranib may have an important role in addressing hyperphagia and underlying obesity associated with this disorder. We will continue to treat, closely monitor and follow patients in the ZAF-311 extension portion of the clinical trial.”
In related news, Boston-based law firm Block & Leviton LLP has filed a lawsuit in the Federal Court in the District of Massachusetts, alleging Zafgen and Thomas Hughes, the company’s chief executive officer, violated Federal Securities Laws. The suit, filed on behalf of company shareholders, alleges that Zafgen made “misleading misrepresentations about thrombotic adverse events in previous clinical trials of its leading drug candidate beloranib. Until October 16, 2015, Zafgen had only ever disclosed two thrombotic adverse events in one prior clinical trial.”
The company, after Oct. 16, reported that there had been four thrombotic adverse events in earlier clinical trials, compared to two that had been previously reported, as well as two more in ongoing studies, for a total of six out of 400 patients. The suit applies to investors who purchased Zafgen stock between Jan. 12, 2015 and Oct. 16, 2015.
Not surprisingly, Zafgen has taken a big hit. Prior to the news, shares traded for $46.23 on Sept. 18. They currently are trading for $10.73 per share. The year’s high was on Mar. 19, 2015, when shares traded for $51.34 per share.
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. Mortality in children with PWS is typically related to respiratory infection and high temperature. In adults with PWS, it is usually associated with circulatory or respiratory problems, as well as other health conditions related to severe obesity.
