DYNE-251 for DMD granted FDA breakthrough therapy designation
Patients amenable to exon 51 skipping would be eligible for treatment
The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to Dyne Therapeutics’ DYNE-251 for the treatment of Duchenne muscular dystrophy (DMD) in patients amenable to exon 51 skipping.
This designation is intended to accelerate the development and regulatory review of medications intended to treat serious conditions. Benefits include enhanced FDA support in development and decision-making, regular communication with the FDA on trial design and regulatory strategy, and eligibility for priority review, which might reduce the time it takes to reach a decision from 12 months to 8 months.
“This Breakthrough Therapy Designation for DYNE-251 is a testament to its potential as a next-generation therapy designed to bring meaningful functional improvement to individuals with DMD for whom exon 51 skipping can lead to the production of near full-length dystrophin,” Doug Kerr, MD, PhD, chief medical officer of Dyne, said in a company press release.
Exon skipping is one therapeutic approach for DMD. This technique involves masking specific protein-coding regions called exons, allowing for the production of a shorter, yet functional version of the dystrophin protein. Such therapies bind to specific regions on the pre-mRNA molecule that is copied over from the DNA template.
Approval also being sought outside US
The FDA’s decision is based on data from the ongoing Phase 1/2 DELIVER clinical trial (NCT05524883), which tested different doses of DYNE-251 versus a placebo in boys with DMD whose mutations are anticipated to respond positively to the exon 51 skipping strategy.
A dose of 20 mg/kg of DYNE-251 administered every four weeks has been selected for testing in registrational expansion groups. A total of 32 patients have been enrolled and data are expected later this year. If positive, the data may support a Biologics License Application that the company expects to submit early next year seeking the accelerated approval of DYNE-251 in the U.S.
Boys diagnosed with DMD have virtually no dystrophin, a crucial protein that helps protect muscles from damage, due to mutations in the DMD gene.
DYNE-251 is an experimental therapy that aims to skip exon 51 of the DMD gene. It consists of an oligonucleotide, which is a small segment of genetic material designed to modify gene activity, attached to an antibody that targets muscle cells specifically. The treatment is administered through infusions into the bloodstream.
Results from the DELIVER trial showed the 20 mg/kg dose resulted in a significant increase in dystrophin levels after up to a year of treatment. A mean absolute level of 3.71% of normal was achieved.
More recent data show the selected registrational dose leads to improvements after 18 months across multiple functional measures, including the Stride Velocity 95th Centile (the maximal speed of strides in a real-life setting), North Star Ambulatory Assessment — commonly used to monitor motor abilities in ambulatory DMD patients — the time to rise from the floor, and the 10-meter (nearly 33 feet) walk/run test.
Dyne is also seeking the approval of DYNE-251 outside of the U.S. The therapy has been granted fast track, orphan drug, and rare pediatric disease designations by the FDA, as well as orphan drug designation by the European Medicines Agency to support its clinical development.
DYNE-251 is the second treatment candidate from Dyne to receive breakthrough therapy designation, following DYNE-101, an investigational therapy for people with myotonic dystrophy type 1 (DM1). Results from the Phase 1/2 ACHIEVE trial (NCT05481879) of DYNE-101 have shown functional improvements in muscle strength, balance, and fatigue, among other benefits.
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