[Updated, 9:17 am ET] Zafgen confirmed this morning that the patient who died in its Phase 3 trial was indeed on its obesity drug, beloranib.
While Zafgen (NASDAQ: ZFGN) still doesn’t know what caused the death of the Prader-Willi Syndrome patient who took beloranib in the trial, the FDA has stepped in nonetheless. The agency has put a partial clinical hold on beloranib, which impacts all ongoing clinical trials of the drug—including two separate Prader-Willi studies in the U.S. and Europe.
“Due to previously reported thromboembolic events in ongoing and prior clinical trials of beloranib and the unknown nature of the death, the FDA gave verbal notice of a partial clinical hold to institute measures to ensure patient safety,” Zafgen said in a statement.
Zafgen shares immediately plummeted 30 percent in pre-market trading on Friday.
In its 10-K earlier this year, Zafgen said that while there were no deaths or serious side effects attributed to beloranib in a mid-stage study of the drug in severely obese patients, there were two “serious thrombotic adverse events” in the study. Zafgen, at the time, said that “may point to the utility of assessment of prior history of thrombotic events in patients enrolled in subsequent trials and added vigilance for [adverse events] related to blood clotting during future clinical trials.”
In the statement today, Zafgen said that all patients in what’s known as ZAF-311—the Phase 3 Prader-Willi study in the U.S.—will be screened for disease related to potential blood clots before getting any more beloranib, and regularly monitored. Since ZAF-311 is already almost completed, the FDA’s move won’t necessarily delay Zafgen here—it still expects to report top-line results from the trial in early 2016. But Zafgen will also take similar precautions in its other trials, including its ongoing Phase 2b study in patients with severe obesity and type 2 diabetes. And it’ll only start its other Phase 3 Prader-Willi trial in Europe after ZAF-311 wraps up and the FDA performs “a full assessment of the safety and efficacy of beloranib.”
[Updated with CEO/CMO comments] In a conference call with analysts Friday morning, CEO Tom Hughes said the death occurred about two weeks ago, and the company then reported the news “very promptly,” within a week, to the FDA.
Chief medical officer Dennis Kim said that the patient was a 23 year old with Prader-Willi who also suffered with a number of other severe health problems and had a body mass index of 55. He was treated with a 1.8 mg dose of beloranib, the lower of the two being tested in the Prader-Willi trial.
Kim said in past beloranib trials, Zafgen has seen six cases of “thrombotic”—blood clot related—findings in 400 patients treated with the drug to date that study investigators have deemed “unrelated or possibly related” to the drug. Those events were pulmonary embolisms and incidences of deep vein thrombosis—one of which, a DVT, occurred in the ongoing Phase 3 Prader-Willi trial.
Though it’s important to reiterate that Zafgen still doesn’t know if the death was related to a blood clot, Hughes noted that the company has started screening patients to see if there’s some “potential interaction” between beloranib and some of the other medications that Prader-Willi patients are already on.
“[Pader-Willi patients] do experience, in many cases, unexpected and very rapid death due to a number of causes,” Hughes said on the call. “We just have yet to understand the underlying cause.”
The news comes at the end of a crazy week for Zafgen, which first reportedly cancelled some investor meetings, and then went silent for two days. Its stock plummeted as investors feared the worst, and then rebounded a bit, ironically, after Zafgen disclosed that a patient had died—but the company didn’t know whether the patient had been taking its drug. For more on the story and Zafgen’s history, check out this piece from earlier in the week.