Less than a year ago, Zafgen was poleaxed by the failure of its lead weight-loss drug beloranib, shedding staff as its share price tumbled. Now, the Boston biotech is back with the first data on a follow-up it hopes will put it back on track.
Zafgen's phase 1 data is for ZGN-1061, a fumagillin-class MetAP2 inhibitor like the ill-fated beloranib, which was placed under an FDA clinical hold before being shelved by the company last July. Patients receiving the drug in trials showed a greater tendency to develop blood clots and there were two deaths.
ZGN-1061 has been billed as a second-generation MetAP2 inhibitor that avoids the thrombotic side effects of its predecessor, and Zafgen now has the first safety data to back up that claim. The phase 1 trial revealed "no evidence of prothrombotic effects", it says, adding that patients also shed weight at a rate of around one pound per week and seemed to have improved blood sugar control.
There were no cases of blood clots or clinically meaningful increases in coagulation biomarkers over the course of the study, which involved 39 patients who received a single ascending dose of ZGN-1061 and 29 subjects on multiple ascending doses over a four-week period, according to the biotech. The efficacy signals were in line with the early results seen with beloranib.
Armed with the data, Zafgen is planning to start a phase 2 trial of the new drug candidate in around 120 overweight or obese people with type 2 diabetes in Australia and New Zealand later this year, according to CEO Tom Hughes, who said the company ended the first quarter with around $117 million in cash and should end the year with more than $65 million in hand. Those reserves should take it through to the end of 2018, when it should have the phase 2 results in hand.
An SEC filing from Zafgen at the end of last month said that the experience with beloranib had allowed the company to develop a "clear and credible explanation for the differences we see for compounds like beloranib compared with compounds like ZGN-1061."
"These studies, informed by discussions with many of the top experts in the thrombosis field, have increased our confidence in the potential of our ZGN-1061 program in specific, and our MetAP2 inhibitor platform in general," it continued.
Specifically, the company has shown that beloranib slowed the proliferation of the endothelial cells lining blood vessels and changes the expression of pro- and anti-clotting factors on their surfaces. ZGN-1061 avoids those effects, in part because it is cleared so rapidly from the blood.
The phase 1 results "mark an important first step in the clinical development of ZGN-1061, which has been optimized to improve glycemic control and body weight, with a favorable safety profile," said Hughes on a conference call.
Before the demise of beloranib, Zafgen was riding high on optimism that MetAP2 inhibitors could unlock the potential in the weight control market, which has been marked by a string of product failures both in development and after commercialisation.
Unlike most weight-loss drugs, which seek to curb appetite or bind dietary fat and clear it from the body before it is absorbed, MetAP2 inhibitors are thought to dial down the amount of fat produced and stored by the body.