The FDA placed a clinical hold on an investigational new drug application for a second-generation MetAP2 inhibitor in development for the treatment of type 2 diabetes, citing cardiovascular safety concerns, Zafgen announced in a press release.
The FDA cited the possibility of CV 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 in the ongoing development of ZGN-1061. The company plans to assess these options and request a type A meeting with the agency to discuss next steps with the program, according to the release.
In the release, the company noted that Zafgen continues to advance its ongoing ex-U.S. phase 2 clinical trial of ZGN-1061, which includes a 1.8-mg dose cohort. Dosing in this clinical trial was recently completed and, while still blinded, no CV safety signals have been observed to date, according to the company.
In June, Zafgen announced positive full results from the its phase 2 clinical trial of ZGN-1061, designed to demonstrate proof-of-concept efficacy and safety in patients with type 2 diabetes and establish a minimally effective dose. The trial met all of its primary endpoints at the 0.9-mg dose, and 12-week data demonstrated a favorable safety and tolerability profile, with no treatment-related serious adverse events and no CV safety signals observed.
“These positive phase 2 data show clinically relevant efficacy, favorable safety profile and dose responsive results in line with our expectations for this proof-of-concept trial in patients with type 2 diabetes,” Thomas E. Hughes, PhD, president and chief scientific officer for Zafgen, said in a press release at the time. “Statistically significant lowering of glucose levels and [HbA1c] was observed, with a curve continuing to show potential for [HbA1c] lowering beyond 12 weeks. Of particular interest, the safety data in this clinical trial were unremarkable and highly differentiated from our first generation MetAP2 inhibitor, with no CV safety signals observed.”
Zafgen said in the statement that it remains on track to report topline data from this cohort in early 2019.
Disclosure: Thomas E. Hughes, PhD, is president and chief scientific officer for Zafgen.