It’s been a turbulent year for Zafgen, to say the least. Two patients died in a Phase 3 clinical trial of its leading drug candidate and, in December, the FDA halted all studies of the drug. Zafgen’s stock tumbled, and shareholders filed lawsuits against the company. The future of the company’s drug, a potential treatment for patients with the rare genetic disorder, Prader-Willi syndrome, fell into deep uncertainty.
But finally some good news: Zafgen (NASDAQ: ZFGN) is revealing today that the drug, beloranib, met both its main goals in the Phase 3 trial. The drug bested a placebo at reducing patients’ weight, and importantly, behaviors related to what’s known as hyperphagia—an insatiable hunger that can lead to severe obesity and even death in Prader-Willi patients. Both results were statistically significant, meaning they weren’t likely to be due to chance.
Shares of Zafgen climbed about 60 percent, to $8.96 apiece, in pre-market trading on Wednesday morning.
The 107 patients who participated in the study were randomly assigned to receive a high (2.4 mg) or low (1.8 mg) dose of beloranib or a placebo twice a week for six months. Patients in the high dose group on average lost 5.3 percent of their initial body weight. Those in the low dose group lost 4.05 percent, while those on placebo gained 4.15 percent.
Zafgen also tallied a score meant to measure patients’ hyperphagia-related behaviors—things like stealing food or being upset when denied food—by having their caregivers fill out a nine-question questionnaire. The higher the score, which ranges from 0 to 36, the worse the patient’s hyperphagia. Patients started with an average score of 16.9 at the start of the trial, and those on the high and low dose of beloranib saw those numbers fall by an average of 7.0 and 6.3, respectively.
How meaningful is a six to seven point drop on that scale? “That’s a remarkable decrease,” says study investigator Merlin Butler, a psychiatry and pediatrics professor at the University of Kansas Medical Center who has been treating Prader-Willi patients for years. “The results look very promising.”
Zafgen CEO Tom Hughes says the data “meet or exceed” the company’s expectations and, at minimum, are the “first crucial step” to getting beloranib approved.
“The data actually give us the opportunity to move forward,” he says.
That’s a subdued response for a company that just hit its goal in a Phase 3 trial. But that’s because Zafgen still has a long way to go. First, it has to figure out what other data are needed before it can file for approval of beloranib. Then it has to convince the FDA to release the clinical hold on the drug, so it can run the studies necessary to accrue that data. And then it has to determine, when beloranib is tested in more Prader-Willi patients, what, if any, correlation exists between the drug and potentially dangerous blood clots like the ones that were responsible for the two trial volunteers’ deaths.
Hughes won’t disclose any specifics about Zafgen’s path forward, other than to say that the FDA had previously asked the company to come back once it had the Phase 3 data to determine the next steps. Zafgen’s “base case” before the FDA stepped in last year, according to Hughes, was to run a second Phase 3 trial of beloranib in Prader-Willi.
“We’ll be back to you with more information about [that] as we learn that from the FDA,” he says.
Those talks will be a welcome occurrence for Zafgen, which has … Next Page »