January 26, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Cambridge, Mass.-based Akashi Therapeutics announced yesterday that after one of its patients in its clinical trial for HT-100 in Duchenne muscular dystrophy (DMD) developed serious, life-threatening health problems, it has halted the trial.
The patient was receiving the highest dose in the HALO trial, 60µg/kd/d. The company hasn’t determined if the patient’s problems are connected to HT-100 or other factors, such as DMD itself.
DMD is a muscle wasting disease caused by mutations in the dystrophin gene. The disease is progressive and generally causes death in early adulthood. Serious complications include heart or respiratory-related problems. It affects mostly boys, about 1 in every 3,500 to 5,000 male children.
“All of us at CureDuchenne are deeply concerned for the health of this young Duchenne warrior,” said Debra Miller, president and chief executive of CureDuchenne to the Boston Business Journal. “We are confident that the team at Akashi will be able to isolate the problem soon. Anti-fibrotic drugs are needed, and CureDuchenne will continue to fund a research pipeline so that we can treat all aspects of this devastating disease.”
Akashi is the third company to recently have problems with a DMD trial. On Jan. 14, 2016, BioMarin Pharmaceutical Inc. announced that the U.S. Food and Drug Administration (FDA) did not approve its application for Kyndrisa (drisapersen) for DMD. In November 2015, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee met and voted not to recommend the drug.
On the same day, the FDA panel declined to recommend Sarepta Therapeutics Inc. ’s own drug for DMD, eteplirsen. That drug isn’t quite out of the running just yet. The FDA was scheduled for a final review of Sarepta’s New Drug Application (NDA) last week, but postponed it because of the pending blizzard that hammered the East Coast.
The rescheduled meeting will be announced in the Federal Register. The Prescription Drug User Fee Act (PDUFA) data is currently scheduled for Feb. 26.
Akashi indicates that it is working with the FDA on resolving the issue. The company stated that, “None of the other patients in the clinical program have experienced a health issue of this kind or of this severity. To date, patients in the three lower-dose cohorts have been treated for between 11 and 19 months with HT-100, amounting to more than 20 patient-years of favorable data, with no other serious events related to the study drug, while this patient has been receiving HT-100 at higher doses for approximately two weeks.”
The clinical trial has been halted while the FDA and Akashi determine if there is a link and evaluate its safety protocols. Earlier safety and efficacy data released in June 2015 were positive, with the patients on the lower doses showing improvement in muscle strength and no serious adverse effects.
On Jan. 8, Akashi announced it had signed a joint drug development program for HT-100 for DMD with Aachen, Germany-based Grünenthal Group. Grünenthal Group is an independent, family-owned, international research-based pharmaceutical group that is present in 32 countries. It employs about 5,300 people worldwide and markets products in more than 155 countries.
HT-100 has been given orphan drug designation in both the U.S. and European Union, and fast track designation in the U.S. As part of the deal, Grünenthal will handle commercialization in Europe and Latin American, while Akashi will hold the rights for the U.S. and other markets.
“We are very excited about this unique collaboration with Akashi,” said Klaus-Dieter Langner, chief scientific officer of Grünenthal, in a statement. “At Grünenthal, we are highly committed to innovation and have been focusing on bringing innovative therapies to patients with high medical need. We are very motivated to use all our strength for the development of HT-100 together with our partners from Akashi and the patient groups supporting them.”
