Akashi Therapeutics has been cleared by the FDA to resume testing an experimental Duchenne muscular dystrophy drug roughly a year after a patient taking the treatment died in a clinical trial. Now the question is whether the Cambridge, MA, company can get the funding to support a new study.
Akashi plans to start a new study of the drug, HT-100, “as quickly as possible,” according to CEO Marc Blaustein. But the timing will depend on financial support from an investor or partner. Blaustein says discussions are underway, but declined to provide more specifics.
The news comes roughly a year after a bad setback for Akashi, a startup formed by two different patient foundations—Charley’s Fund and the Nash Avery Foundation— to acquire and finance the development of treatments for Duchenne. In January 2016, Akashi suspended a Phase 1b/2a clinical trial of HT-100, a drug meant to improve the muscle strength of Duchenne patients, after a patient who had been on a high dose of the drug for two weeks began experiencing “serious, life threatening issues.” Akashi didn’t say specifically what those issues were at the time, but reported the next month that the patient had died. The company has since been working with the FDA to find out what happened.
At the time, Akashi said it was the first time any serious health issues had cropped up in the testing of HT-100, a pill that contains halofuginone, a potential remedy for the malformed muscle fibers and inflammation associated with Duchenne.
According to Blaustein, Akashi found that taking HT-100 along with repeat doses of the anti-nausea drug ondansetron (Zofran) led to unusually high levels of halofuginone in the patient’s body. The patient’s blood pressure fell dangerously low, leading to “numerous” complications, he says.
There is usually a “multi-day early-warning” before any serious health problems related to HT-100 occur—patients throw up or have other stomach problems—but those issues were masked by ondansetron, Blaustein says. In the new study, a mid-stage trial, no patients will be allowed to use anti-nausea medication.
“Physicians and patients will be made aware of [this],” he says. “Patient safety is of utmost importance to us.”
Akashi has seen patients’ muscle strength improve even at the lowest tested dose of HT-100, 300ug per day. But in the new trial Akashi is going even lower than that, to 150ug, a dose that hasn’t been tested in humans yet. Akashi still believes the drug will be effective. “Lower doses tested appeared to have as significant an effect on muscle strength, if not a more significant effect, as higher doses tested,” Blaustein says.
Duchenne is a progressive and deadly genetic disease affecting roughly 300,000 worldwide. It typically robs patients of their ability to walk by their teens and kills them at a young age from lung or heart problems. After decades without any treatments, two were approved in the U.S. over the past year: eteplirsen (Exondys 51) and deflazacort (Emflaza).
Neither, however, are cures. Eteplirsen, from Sarepta Therapeutics (NASDAQ: SRPT), is meant to slow the progression of the disease, but for just a 13 percent genetic subset of Duchenne patients. The steroid deflazacort—which has been available for years in other countries—was approved in the U.S. in February for all Duchenne patients, but also only helps temporarily delay the disease’s grim march. (Deflazacort hasn’t launched yet; Marathon Pharmaceuticals sold the drug’s rights to PTC Therapeutics (NASDAQ: PTCT) last week).
There are a number of other drugs in development, including gene therapy and gene editing treatments. Drug combinations are also being tested, and that’s where Akashi sees its own experimental treatments—HT-100, DT-200, and AT-300—fitting in going forward. DT-200, meant to build muscle mass, is in Phase 1 trials, while AT-300, which is supposed to prevent muscle loss, is currently in preclinical testing. Akashi needs partners to help fund the studies of those two drugs as well, Blaustein says.