BOSTON (TheStreet) -- Developing a drug successfully means hitting the right balance between efficacy and safety. Approvable drugs demonstrate a benefit for patients that outweigh the risks of side effects.
Zafgen (ZFGN) - Get Zafgen, Inc. Report is in a tough spot now because the benefit-risk of its lead pipeline drug beloranib is not clear. The patient who died while taking beloranib as part of Zafgen's clinical trial was already extremely ill. Just 22 years old, his rare disease, Prader-Willi Syndrome, causes compulsive overeating and severe obesity. His body-mass index of 55 implied he weighed more than 380 pounds, assuming average adult height.
But as disclosed Friday, the U.S. Food and Drug Administration placed Zafgen's clinical trials on partial hold because of safety concerns tying beloranib to an increased risk of potentially dangerous blood clots.
Zafgen shares fell 30% to $14.76 in recent trading.
It's not yet known if a blood clot, or thrombotic adverse event, contributed to the patient's death in the clinical trial. Zafgen, however, disclosed Friday that six patients in previous and current trials reported thrombotic adverse events, including blood clots in the legs, and more seriously, in the lungs. All six patients were treated with beloranib. By comparison, no patients in placebo arms of Zafgen's trials reported thrombotic adverse events. Zafgen has enrolled about 400 patients in all its studies combined.
Beloranib belongs to a class of drugs which block an enzyme, MetAP2, believed to play a role in metabolism. MetAP2 inhibitors are also anti-microbials and have a blocking effect on angiogenesis, or the growth of new blood vessels, which has led to some of the drugs in the class to be studied in cancer. Roche's (RHHBY) Avastin, a blockbuster anti-angiogenesis cancer drug, has prominent safety warnings in its label describing arterial and thrombotic adverse events. Zafgen doesn't believe beloranib, at the lower doses used in its trials, have exhibited any anti-angiogenic effects, but the company cannot rule it out either.
Zafgen is now making amendments to its beloranib trial to better screen out patients at high risk for blood clots and make sure patients treated with beloranib are monitored more closely. But patients with Prader-Willi syndrome or who suffer from severe obesity are almost, by definition, at higher risk for blood clots. Zafgen's challenge is to find a way to prove beloranib can help these severely ill patients without putting them at increased safety risk.
Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback; click here to send him an email.