FDA places hold on study of Zafgen's experimental diabetes drug ZGN-1061

Zafgen announced Monday that the FDA has placed a hold on the first US clinical trial of ZGN-1061, the company's second-generation, investigational MetAP2 inhibitor under development for type 2 diabetes. According to Zafgen, the FDA cited the "possibility of cardiovascular safety risk based on the company's prior compound and outlined multiple potential paths for moving forward, including nonclinical or clinical options, to address these concerns." The company, whose shares dropped as much as 43 percent on the news, indicated that it will review its options and ask to meet with the FDA to discuss next steps with the programme.

Zafgen said its ongoing ex-US Phase II study of ZGN-1061, which includes a 1.8-mg dose cohort, continues to move ahead. The company noted that although the study remains blinded, no cardiovascular safety signals have been observed to date, with topline results from this cohort anticipated early next year. 

In June, Zafgen unveiled positive 12-week results from the initial cohort of the mid-stage study, which included doses up to 0.9 mg. In addition to significantly reducing A1c levels at the 0.9-mg dose versus placebo, Zafgen said ZGN-1061 also had a favourable safety and tolerability profile, with no treatment-related serious adverse events or cardiovascular safety signals observed.

Commenting on the FDA hold, Leerink Partners analyst Joseph Schwartz said the agency's decision was not surprising because preclinical data suggest that ZGN-1061 has the potential to cause blood clots. Schwartz also pointed out that Zafgen has not discussed how the body metabolises the drug, how it 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," the analyst remarked.

Meanwhile, Zafgen noted that given the hold on the US study of ZGN-1061, it expects its cash runway will extend through 2020, "with sufficient capital through multiple milestones."

The company's first drug, the MetAP2 inhibitor beloranib, was developed to treat obesity. Zafgen ended development of the therapy in 2016 following two patient deaths in the Phase III bestPWS study, which included patients with Prader-Willi syndrome. 

-----------------------------------------------------------------------
Editor's Note:

To apply for becoming a contributor of En-CPhI.cn,

welcome to send your CV and sample works to us,

Email: Julia.Zhang@ubmsinoexpo.com.