Zafgen took a big hit last year when two patient deaths forced it to abandon its most advanced drug, belaronib. The company is now looking to a new experimental weight loss drug for diabetics to turn its fortunes around, with the first glimpse at early data released this afternoon.
Many caveats apply. The data are from a short, small Phase 1 trial. The drug, ZGN-1061, has to prove in much larger, longer studies that it can safely lead to significant weight loss to have a chance to be a commercial product someday.
But the drug is critical for Boston-based Zafgen (NASDAQ: [[ticker:ZFGN]]), which has said ZGN-1061 should be just as effective as beloranib and much safer, to boot. When the patient deaths came to light in late 2015, the FDA suspended testing of beloranib and Zafgen cut short the trials that had been underway. In July 2016, Zafgen shelved the drug, shares plummeted to all-time lows, and the company cut 34 percent of its staff and put all its resources behind ZGN-1061. Leerink Partners analyst Joseph Schwartz wrote recently, “The future of the company now rests on ZGN-1061’s success.”
Like beloranib, ZGN-1061 is an injectable small molecule drug that is supposed to stimulate the body to burn more fat. It blocks the activity of an enzyme called methionine aminopeptidase 2. The drug is being developed, initially, for patients with type 2 diabetes who are also obese.
The first human data from ZGN-1061 show that 22 overweight or obese patients received either a low (0.2 mg), medium (0.6 mg), or high (1.8 mg) dose of ZGN-1061 twice a week for four weeks. Seven received a placebo.
Those on ZGN-1061 lost an average of 4.6 pounds (low dose), 2.2 pounds (medium), or 3.8 pounds (high), respectively, after four weeks of treatment, while placebo patients lost 0.51 pounds. But the company would not disclose how much the patients had lost as a percentage of body weight. Without percentages, it’s impossible to know how significant the weight loss is.
Zafgen CEO Tom Hughes, who has led the company since 2008, says those numbers are “a drop shy” from early testing of beloranib in the past. He expects the weight loss effect will be identical once the drug is tested in a large group of exclusively diabetics. “We’re pretty confident we’ll have a very strong effect once we get into the right population,” Hughes says.
The deaths in the beloranib trial were due to pulmonary embolism—a blood clot that gets lodged in an artery in the lungs. Hughes says there has been no evidence of blood clotting effects in ZGN-1061 so far. (Zafgen also tested different doses of ZGN-1061 in 28 healthy volunteers.) The most common side effects seen so far with ZGN-1061 were mild gastrointestinal issues and headaches.
These results are just a start for Zafgen. It will dose at least 100 obese type 2 diabetes patients with ZGN-1061 in a Phase 2 trial expected to start later this year and produce data in 2018, according to chief medical officer Dennis Kim. It’s important to note that beloranib also produced striking weight loss early on, but serious blood clots didn’t occur in patients until larger, longer trials. Hughes, though, says because of Zafgen’s experience with beloranib, it is now proactively measuring patients taking ZGN-1061 for a number of other markers indicative of clotting. “We didn’t know at the time that beloranib would pose such a risk,” he says.
Zafgen was developing beloranib for the rare genetic disease Prader-Willi Syndrome, which causes a dangerous, insatiable hunger. It could have been the first approved Prader-Willi drug in more than 15 years. (Xconomy detailed the saga, and its impact on the Prader-Willi community, here.)
For now, the company will steer ZGN-1061 clear of rare, severe obesity-related conditions.
“We have some work to do first,” Hughes says.
