Dyne another day: DMD therapy back on track after FDA lifts clinical hold

Duchenne muscular dystrophy-focused Dyne Therapeutics is back on track to move its first asset into the clinic in the coming weeks after the FDA lifted a clinical hold on the drug.

The agency hit the pause button on the trial application for the therapy, DYNE-251, in January and requested additional clinical and nonclinical information.

“The clearance of our first IND is an important achievement for Dyne, and we appreciate the partnership with the FDA throughout this process,” Dyne CEO Joshua Brumm said in a statement announcing the lift Tuesday.

The FDA's decision means Dyne can still stick to its original timeline of entering the drug into phase 1/2 trials for both DMD and myotonic dystrophy type 1 in “mid-2022.” The DMD trial will cover between 30 and 50 ambulant and non-ambulant males with the disease aged between 4 and 16 years old who have mutations amenable to exon 51 skipping therapy.

Exon skipping is a form of RNA splicing to allow cells to “skip” over faulty or misaligned sections of genetic code. In patients with DMD, one or more of the 79 exons in the dystrophin gene are deleted, which interferes with the rest of the gene being pieced together.

DYNE-251 is designed to skip over exon 51. Dyne also has a number of preclinical assets coming down the road, which target DMD mutations amenable to skipping other exons, including 53, 45 and 44.

There is currently no cure for the muscle wasting disease, which affects up to 15,000 people in the U.S. and 25,000 in Europe. Loss of strength and function typically first appears in preschool-age boys and worsens as they age.

The FDA’s move didn’t appear to impress investors, with Dyne’s share price dropping almost 4% to $6.92 in the market’s opening hour Tuesday. 

DMD therapies have sometimes proven a risky bet. Astellas’ gene therapy strategy was further scuppered in April when the Japanese pharma scrapped its DMD candidates after assessing the preclinical data, while Sarepta’s RNA therapy for the disease was flagged for some serious adverse events last year.