January 20, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Boston-based Zafgen announced today that despite setbacks, its drug ZAF-311 (beloranib) being studied in Phase III trial in patients with the rare Prader-Willi syndrome (PWS) showed positive results.
On Oct. 14, 2015, Zafgen announced that a patient had died during the study. The U.S. Food and Drug Administration briefly halted the trial pending further investigation. Shortly afterward, the Phase IIb and Phase III trials continued. But in December, the company was informed that a second patient had died. The cause of death of the first patient was “respiratory failure due to pulmonary emboli.” The FDA froze the trial.
The second patient to die 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.
PWS is a rare genetic disorder. It’s 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.
PWS patients are already at higher risk of morbidity and mortality, with an approximate death rate of three percent annually compared to one percent per year for the general population. Childhood mortality in PWS patients is typically related to respiratory infection and high temperature. In adults, it is usually associated with circulatory or respiratory problems, as well as other health conditions related to severe obesity.
Zafgen indicated today that the drug, a MetAP2 inhibitor, met its co-primary efficacy endpoints, showing a statistically significant reduction in body weight and hyperphagia-related behaviors. Hyperphagia is an abnormally increased appetite.
“This clear efficacy outcome is a crucial first step in moving discussions forward with the Food and Drug Administration regarding continued development of beloranib,” said Thomas Hughes, Zafgen’s chief executive officer, in a statement. “While we take the previously reported adverse events very seriously, we now have the robust data to provide greater perspective on the benefit/risk relationship of beloranib in this high-risk patient population.”
Zafgen plans to provide all the efficacy and safety data to the FDA from both trials. “We’re delighted with the results,” Hughes told The Boston Globe. “This is the first demonstration of a clinical benefit against two of the major issues that affect this patient population. Our intention is to provide a plan for moving forward with an emphasis on patient safety.”
Beloranib’s mechanism is to reduce the body’s fat production, as well as burning excess fat as fuel. It’s a different mechanism that other obesity drugs, such as those marketed by Vivus Inc. , Orexigen Therapeutics, Inc. and Arena Pharmaceuticals, Inc. Those drugs typically suppress appetite by affecting nerve signals, which tricks the brain into believing the stomach is full.
The trial results, so far, do not appear to address a link between the drug and the blood clotting. “As of today,” Hughes told The Boston Globe, “we have no evidence to suggest that Beloranib by itself can cause blood clots. This is a patient population that’s at risk for thrombotic [clotting] issues.”
The FDA’s clinical hold kept the company from completing the trial, but Dennis Kim, Zafgen’s chief medical officer, indicates that the trial was mostly completed.
Zafgen was battered by reports of the previous deaths, but showed some positivity after today’s news. Shares traded for $46.23 on Sept. 18, 2015, plunged to $11.49 on Oct. 19, and recovered slightly to $17.69 on Nov. 27. Then the news of the second death broke and shares dropped to $5.63 on Dec. 4. Shares are currently trading for $9.56.
