Zafgen's second try at Prader-Willi syndrome triggers another safety alarm in preclinical tox study
Zafgen’s $ZFGN latest shot at creating the first therapy to treat patients with rare cases of obesity brought on by Prader-Willi syndrome has hit a safety alarm before the drug even managed to make it into the clinic.
The successor to beloranib — which blew up with spectacular effect several years ago following a clinical hold by the FDA — ZGN-1258 was supposed to be the biotech’s comeback drug in the field. Instead, the biotech reported after the market closed on Monday that it is suspending plans for an IND after researchers tracked muscle deterioration in a rodent model of the disease.
Zafgen’s stock shriveled at the mention of a new safety alert. The shares plummeted 35% after the bell.
From their statement today:
Nonclinical data showed degeneration and other anomalies in rat muscle tissue to different degrees in both vehicle and dose arms of the studies. The effects were absent from other animal species in long term models, and importantly, this finding has not been observed in any of the Company’s other MetAP2 inhibitors or clinical trials and appears to be specific to ZGN-1258. Zafgen will provide an update on plans for ZGN-1258 at a later time, if warranted, following further evaluation.
The move to shelve the IND came after Zafgen reported in an SEC filing late last year that everything had been lined up to initiate clinical trials except for 1 last preclinical trial, which had to be redone by a new CRO after the first CRO had conducted it “improperly.”
Any fresh hint of a safety warning is toxic to Zafgen, which had to reorganize and ultimately replace the senior execs who went on to other endeavors after the first big crash. The biotech recently reported what it called encouraging early data about their lead drug, ZGN-1061 for obesity related to diabetes. Researchers reported positive improvements in weight loss and blood sugar levels for diabetics.
The lead drug, though, has also been under a cloud since the FDA dropped a clinical hold on the program last November, citing CV safety concerns. Leerink’s Joseph Schwartz has remained focused on a key biomarker for CV risk, even as the company pursued a risky ex-US trial.
Diabetes is a field with a huge patient population, and even a hint of a safety issue could prove lethal for any drug in development for this group.
And obesity drugs in general are always under a microscope at the FDA, even after the latest generation hit the market, though they proved dramatically unsuccessful as a commercial product.