Zafgen ($ZFGN) has rolled out a fresh set of upbeat efficacy data for its obesity drug beloranib, trumpeting evidence of significant weight loss among diabetics while taking a much more low-key approach to pointing to fresh evidence of the safety issues that forced the FDA to halt all use of the drug.
Zafgen's 1.8-mg and 1.2-mg doses of beloranib in the Phase IIb study triggered a 12.7% and 13.5% drop in body weight, compared with a 3.1% drop for the placebo arm. And there was an average reduction in HbA1c of 2% for the two drug arms compared to a reduction of 0.6% for placebo.
That's all to the good for the biotech, which has been bullish about this drug's ability to take off pounds in a way currently marketed therapies can't. But the past three months have been brutal on the company, which initially chose to stay mum about a patient death in their Phase III study for Prader-Willi syndrome which they subsequently determined was caused by a pulmonary embolism. Subsequently another patient taking the drug died, also from a pulmonary embolism, forcing the FDA to order a complete stop to any further dosing.
The company, though, was far enough along with its two most advanced studies to wrap the trials and report out data. Now Zafgen plans to assemble a risk mitigation plan and take that to the FDA in an attempt to open the door to moving ahead.
That's going to be a tall order, though, as this latest study offered fresh evidence of the lethal side effects triggered by a drug that's being advanced for both rare diseases as well as big patient populations like diabetes, where the bar on safety is set very high by regulators.
"In the clinical trial," Zafgen reported today, "there were a total of nine serious adverse events identified in eight patients, one in the 1.8 mg group, six in the 1.2 mg group, and two in the placebo group. As previously disclosed, one of the SAEs was a pulmonary embolism in the 1.2 mg treatment group. During the VTE (venous thromboembolism) screening process that followed the FDA's partial clinical hold of the beloranib IND in October 2015, two additional VTEs were identified in patients in this clinical trial: deep vein thrombosis in a patient who had received 1.8 mg of beloranib, and superficial thrombophlebitis in a patient who had received 1.2 mg of beloranib."
Zafgen execs, though, believe they can blaze a trail forward.
"These results reinforce the strong efficacy profile of beloranib and further inform the potential of our MetAP2 inhibitor platform to impact metabolic disorders," said Zafgen CEO Tom Hughes in a statement. "In addition to the recent positive efficacy data from our bestPWS clinical trial, these data provide additional context regarding beloranib's benefit-risk profile in the treatment of severe forms of obesity. We look forward to discussing these results with the FDA as we work to establish a path forward for beloranib in Prader-Willi syndrome and other orphan obesity indications."
Shares of Zafgen surged 11% this morning, but the stock is still trading at just a fraction of its peak in the fall of last year.
- here's the release