The Cambridge, Mass.-based biotech is disclosing Thursday evening the first human data on ZGN-1061. This is a second-generation compound that Zafgen started to develop after the abandonment of its first obesity drug beloranib due to the deaths of two patients in late 2015.
In this first study, Zafgen administered ZGN-1061 to 50 overweight and obese, but otherwise healthy, people and saw no evidence of blood clots or meaningful increases in biomarkers like D-dimer that can be a warning sign for blood clots. About half the people received ZGN-1061 injections twice a week for four weeks.
On average, the people treated with ZGN-1061 for four weeks lost approximately one pound per week.
Efficacy aside, Zafgen was especially keen to get these new safety data on ZGN-1061 because blood clots in the lungs caused the death of two patients with Prader-Willi Syndrome, a rare obesity-related disease, treated with beloranib in a phase III study.
The deaths, reported in late 2015, led to an FDA-imposed clinical hold on the beloranib trial. Zafgen's stock price fell off a cliff. Patients with Prader-Willi suffer from an insatiable appetite and can eat themselves to death. Beloranib was able to curb patients' never-ending drive to eat but the drug's safety risk proved unacceptable. In July 2016, Zafgen made the decision to shelve beloranib, restructure the company and focus development efforts on ZGN-1061.
Zafgen has spent the past 20 months sleuthing why beloranib caused deadly blood clots and making sure, through extensive animal studies and now the first human study, that ZGN-1061 is a safer compound.
"We holed up for awhile and went into problem-solving mode. The problems never end but at the same time we are feeling very good about the results we've just gotten and it is onward from here," said Zafgen CEO Tom Hughes in an interview Wednesday. Zafgen shared the ZGN-1061 data with me under an embargo.
Onward means advancing ZGN-1061 into a phase II study later this year. The study will enroll approximately 120 patients with obesity associated with Type 2 diabetes. Three doses of ZGN-1061 will be investigated against a placebo to measure the drug's ability to lower hemoglobin A1c (blood glucose levels), weight loss and other diabetes-related endpoints. [Zafgen decided not to pursue development of ZGN-1061 in Prader-Wili.]
Before it was discontinued, a study of beloranib in obese, Type 2 diabetics demonstrated a 2% drop in blood glucose after six months of treatment compared to a reduction of 0.6% in placebo patients.
Diabetes is a crowded and competitive field in which to develop a new drug, particularly given recent pricing pressures. But if ZGN-1061 can match the blood glucose-lowering efficacy of beloranib with a cleaner safety profile, Hughes believes the drug could prove valuable in the diabetes treatment market, particularly in patients who might otherwise need to start daily insulin injections. Those plans will depend, of course, on more ZGN-1061 data, including longer-term safety, than what Zafgen is unveiling Thursday.
At its $4.87 close on Thursday, Zafgen shares are up more than 50% this year, but the company was trading above $45 per share in 2015 before the beloranib problems surfaced.
Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback; click here to send him an email.