about 40.3 years. The patients had BMI’s anywhere from over 30 to over 50, so Zafgen could see how well each dose worked in people of varying body weight. Zafgen enrolled both men and women—though Hughes wouldn’t give the gender breakdown as of yet—and tested the drug’s safety and tolerability over the course of 12 weeks. Similar-sized groups of patients were given twice-weekly injections of beloranib at a 0.6 mg (37 patients), 1.2 mg (37 patients), or 2.4 mg (36 patients) doses, or a placebo injection (38 patients) instead, according to the release.
Hughes said that the company found that there were no new health or tolerability issues that cropped up with people taking the drug for a longer period of time (an earlier study tested the drug over a four-week period).
The most common side effects experienced by patients during the study were nausea, vomiting, diarrhea, and trouble sleeping. Hughes says that the sleeping problems primarily occurred at the highest dose level. He declined to specify how many patients total dropped out of the study. Zafgen will release the full results of the clinical trial towards the end of the summer, according to Hughes.
“Overall the effects we see in terms of diarrhea, nausea and vomiting, these are not particularly pronounced and they do not differentiate from placebo in many ways,” he says. “But it is something that is there.”
Hughes says that during treatment people would both end up eating less and changing their food preferences. He suggests that some of the gastrointestinal problems seen in patients so far, then, could reflect either dietary changes, or the fact that they’re just not taking in as much food. He also added that those side effects are “very, very modest” compared to the diarrhea, nausea and vomiting experienced by patients on mainstay diabetes drugs such as metformin.
“I think our profile overall is actually looking pretty good—and these are not safety issues,” he says.
The results are encouraging, but Zafgen knows it has to reproduce them over a larger scale, and a much longer time span, to really get the attention of regulators. The mid-stage trial was a 12-week study only because that was the longest study it could devise that was supported by the animal safety data it had at the time, according to Hughes.
Zafgen is currently running the last animal safety studies it needs to before it can begin a much longer clinical trial, and plans to start one that would evaluate the drug over the course of six months to a year. The doses in that study will be between 0.6 mg and 2.4 mg. Zafgen may explore a 1.8 mg dose going forward, but will probably keep at least two doses for the next trial, according to Hughes.
“I think we have a nice working range to move forward,” he says. “The good news is that the weight loss is rather pronounced, and it’s ongoing even towards the end of the 12 week treatment. That bodes well for continued efficacy.”
Zafgen plans to position the drug as an alternative to bariatric surgery, a procedure by which surgeons alter or block portions of a patient’s digestive system. That gives it a target population of about 15 to 18 million people in the U.S. alone, according to Hughes.
“We like that approach because it does target the therapy towards people with a clear-cut medical need and where the benefit would be easiest to address, and we think that also provides economic advantages and would help us with adoption of the drug overall,” he says.
It also wants to look at beloranib not just as a weight loss treatment, but to help curb diabetes as an alternative to what is known as metabolic surgery—bariatric surgery used to help slow symptoms of type 2 diabetes.
Hughes says Zafgen has interest from not only potential partners and acquirers, but also investors who see an IPO as a good way to cash in on Zafgen. The company has raised just under $70 million in VC money total from Atlas Ventures, Third Rock Ventures, and Alta Partners. It has enough cash to get it through the end of the year, and is currently looking to raise more. Zafgen feels good about its ability to do so.
“We’re quite aware of how favorable the IPO environment is these days, and this is something that we’re contemplating as well,” he says. “We’re quite content with our optionality right now.”
