The FDA has ordered Zafgen to suspend a mid-stage study testing its experimental diabetes drug, an apparent precautionary move.
A clinical hold halts patient enrollment and also stops already enrolled patients from receiving the study drug due to a potential safety risk. No safety problems have been reported for the drug, ZGN-1061, so far. But Zafgen (NASDAQ: ZFGN) said Monday that the FDA’s letter cited the “possibility of cardiovascular safety risk” based on the company’s earlier obesity drug, which acts in a similar way as ZGN-1061. Two years ago, the deaths of two patients in a late-stage study of the obesity drug led Boston-based Zafgen to abandon further development of the compound. The patients died of pulmonary embolisms—blood clots that break loose from a leg or other part of the body and get lodged in an artery in the lungs.
Shares of Zafgen fell more than 43 percent after the disclosure of the clinical hold Monday morning.
Zafgen develops drugs to treat metabolic disorders. The company’s first drug, beloranib, was developed to treat rare forms of obesity, among them Prader-Willi syndrome. That drug blocked an enzyme called methionine aminopeptidase 2 (MetAP2) that is involved in removing methionine, an amino acid needed in tissue repair.
Like beloranib, ZGN-1061 is also a MetAP2 inhibitor. The company has already reported that the diabetes drug met the main goals of a Phase 2 study testing a range of doses up to 0.9 mg. The drug’s safety profile was comparable to a placebo and no serious side effects or cardiovascular problems were observed, the company said.
In the ongoing Phase 2 tests of ZGN-1061, a group of patients is being treated with a 1.8 mg dose. Zafgen said that dosing in the study was recently completed and no cardiovascular problems have been seen so far. The company added that preliminary data from that study are expected early next year.
In a research note, Leerink Partners analyst Joseph Schwartz wrote that the clinical hold was not completely surprising because preclinical data suggest that the Zafgen diabetes drug has the potential to lead to blood clots. He added that the company has not discussed how the body metabolizes the drug, how the compound enters and exits cells, and how it is cleared from the body.
“Without such basic disclosures from the company, and the preclinical work showing that ZGN-1061 may induce pro-clotting factors if it is trapped in endothelial cells for 72 hours, we have viewed the aforementioned variables as significant risks as they could place patients at risk for developing lethal blood clots,” Schwartz wrote.
In its news release disclosing the clinical hold, Zafgen said that the FDA suggested multiple paths for moving its diabetes drug forward that would address its concerns. The company did not describe details of those suggested options, but said it plans to assess them and ask for a meeting with the regulator to discuss next steps.