Safety Issues Spur Foundation-Backed Akashi to Suspend Duchenne Trial

Xconomy Boston — 

It’s been a roller coaster few months for the community of caregivers and patients with Duchenne muscular dystrophy, a progressive and ultimately fatal genetic disease. One potential treatment from BioMarin Pharmaceutical was rejected by the FDA. Another from Sarepta Therapeutics sits in regulatory limbo after Winter Storm Jonas delayed an advisory panel. And now a third, from Akashi Therapeutics, has a safety issue that’ll have to be resolved before clinical testing can continue.

Akashi, the Cambridge, MA-based startup formerly known as Dart Therapeutics, said this morning that it’s suspended a Phase 1b/2a clinical trial of HT-100, an experimental treatment for Duchenne. Akashi said that a patient on the highest dose of HT-100 in the trial is “experiencing serious, life threatening health issues.” Akashi didn’t say specifically what those issues are, and doesn’t know yet to what extent they are related to its drug, or other factors, but it’s working with the FDA to find out what happened.

It’s unclear how long the trial will be stopped for: “As we are at the very beginning of the investigation, we cannot provide a projected timeline,” Akashi said. “As always, our first priority is patient safety.”

Akashi said that this is the first time any serious health issues have cropped up in testing of HT-100, a pill that contains halofuginone, a potential remedy for the malformed muscle fibers and inflammation associated with Duchenne. Akashi says it’s accrued more than 20 patient years of data on patients in lower-dose groups in the trial, each of whom has been treated for between 11 and 19 months without any significant health problems and with some early results supporting “improvement in muscle strength.” The patient with the health problem was on a higher dose of HT-100 for about two weeks.

It’s bad timing for Akashi, which just inked a $100 million partnership with German firm Grunenthal Group on HT-100 two weeks ago. But it also represents another recent delay of a potential treatment for Duchenne. The disease, which affects roughly 300,000 people (primarily boys), causes a progressive decline in muscle function, and typically an early death from complications including respiratory failure. There are no approved effective treatments for it in the U.S. (PTC Therapeutics won conditional approval of a Duchenne drug called Ataluren in Europe in 2014).

BioMarin (NASDAQ: BMRN) was on the doorstep of a potential FDA nod, but the agency rejected its drug candidate, drisapersen, a few weeks ago, saying that the “standard of substantial evidence of effectiveness has not been met.” And the prospects for Sarepta’s (NASDAQ: SRPT) experimental drug eteplirsen were thrown into question following the release of FDA documents that slammed Sarepta’s data.

The FDA has yet to reschedule an advisory panel on eteplirsen after postponing the event last week; the agency is supposed to decide whether to approve the drug by Feb. 26. (I wrote in November about the landscape for prospective Duchenne treatments, and the advisory panels for BioMarin and Sarepta’s drugs.)

Akashi has two other drugs, DT-200 and AT-300, in early stage and preclinical testing. Those studies aren’t affected by today’s trial suspension. The company is unusual, as far as biotechs go. It was formed by non-profit disease foundations—Charley’s Fund and the Nash Avery Foundation—as a vehicle to acquire and finance the development of treatments for Duchenne. The company, for instance, bought DT-200 from Belgium’s Galapagos NV and AT-300 from Tonus Therapeutics, of Buffalo, NY.