FDA hits Zafgen’s beloranib successor with clinical hold

FDA
Zafgen is currently assessing the multiple potential paths forward before meeting with the FDA. (Andrew Harnik/Associated Press)

The FDA has placed a clinical hold on Zafgen’s ZGN-1061. Zafgen suffered the blow after failing to allay the FDA’s concerns that ZGN-1061 will face similar cardiovascular safety problems to its predecessor, beloranib.

Obesity drug beloranib went off the rails in 2015 and 2016 when patient deaths in phase 3 forced Zafgen to ditch its then-lead candidate. Zafgen responded to the setback by prioritizing the progress of follow-on candidate ZGN-1061. Like beloranib, ZGN-1061 is a MetAP2 inhibitor. Unlike beloranib, Zafgen thinks it has reason to believe ZGN-1061 will have a good thrombotic safety profile.

Zafgen has spent the past year putting that idea to the test in a phase 2 trial of ZGN-1061 in patients with Type 2 diabetes. Speaking in 2017, Zafgen framed its decision to run the trial in Australia as a consequence of having tested beloranib extensively in the country.

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Now, a supplementary explanation has emerged: The FDA has reservations about ZGN-1061. Zafgen sketched out the reservations in a statement that revealed the FDA placed a clinical hold on the IND for the planned U.S. trial of ZGN-1061. The FDA “cited the possibility of cardiovascular safety risk” based on beloranib, according to Zafgen.

The brief statement from Zafgen offers few clues about how long the clinical hold will be in place. Zafgen is currently assessing the “multiple potential paths for moving forward, including nonclinical or clinical options” proposed by the FDA ahead of a meeting with the agency.

Zafgen found the FDA unwilling to sign off on its proposed study despite early-phase trials outside the U.S. supporting the view that ZGN-1061 is safer than its predecessor. The Boston-based biotech is yet to see cardiovascular safety signals in its phase 2 trial, and posted clean phase 1 data in 2017.

The encouraging clinical data on ZGN-061, notably the low-dose phase 2 results posted in June, have helped Zafgen recover somewhat from its post-beloranib blow-up slump. Shares in Zafgen have risen by more than 100% over the past year, although the stock remains well down from the highs it hit back in 2015 when beloranib was still advancing through late-phase development.

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