Dyne, citing positive trial data, to ask FDA to approve DMD therapy
Exon-skipping DYN-251 boosts dystrophin, improves motor function
Dyne Therapeutics said it plans to ask the U.S. Food and Drug Administration (FDA) to approve DYNE-251, its exon-skipping therapy for people with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping, after a Phase 1/2 trial showed encouraging results.
Data from the registrational expansion cohort of the DELIVER trial indicated that DYNE-251 is capable of boosting levels of the dystrophin protein, with clinical data suggesting hints of improved motor function in patients receiving the therapy.
“With these unprecedented clinical data in hand, we are on track to submit for U.S. Accelerated Approval in Q2 2026, positioning us for a potential Q1 2027 launch, assuming Priority Review, into an established market of approximately 1,600 people with significant unmet need,” John Cox, Dyne’s president and chief executive officer, said in a company press release.
Dyne plans to use these data, particularly the increase in dystrophin protein levels, as a basis to request accelerated approval from the FDA for DYNE-251. This type of approval is conditional, granted based on early clinical evidence that a therapy is likely to benefit patients. Developers of drugs granted accelerated approval are required to conduct additional testing to confirm clinical benefit, with continued approval contingent on the results of these tests.
Several exon-skipping therapies for DMD have been granted accelerated approval based on clinical data showing increased dystrophin expression.
Skipping exons
DMD is caused by mutations that result in low levels of dystrophin, a protein essential for muscle health. Muscle cells that lack dystrophin accumulate excessive damage over time, ultimately leading to DMD symptoms including muscle weakness and wasting.
The gene that encodes dystrophin includes sections called exons. The exons in a cell’s DNA are interspersed with sequences that don’t code for protein, instead helping regulate gene activity. When the gene is read to produce protein, the entire sequence is copied into a temporary molecule called messenger RNA, and then the exons are strung together to form a mature sequence that can be used to make the dystrophin protein.
Some DMD-causing mutations cause exons to fall out of alignment, resulting in a garbled mature sequence and the inability to produce dystrophin protein. Exon-skipping therapies aim to remove certain exons in order to get the rest back into alignment, enabling production of a shortened but functional dystrophin protein. DYNE-251, also known as zeleciment rostudirsen (z-rostudirsen), is designed to treat DMD patients with mutations amenable to exon 51 skipping.
The Phase 1/2 DELIVER clinical trial (NCT05524883) tested DYNE-251 against a placebo in boys with DMD ages 4 to 16. The first part of the study tested various doses of DYNE-251 in 54 patients, with the goal of identifying an optimal dose for further testing. Ultimately, a dose of 20 mg/kg, given by infusion every four weeks, was chosen for further testing in the registrational expansion cohort, which tested this dose against a placebo in an additional 32 patients.
The main goals of the trial were to assess DYNE-251’s safety and its effects on dystrophin protein levels. Results from the registrational expansion cohort showed that, after six months, dystrophin levels in muscles of DYNE-251-treated patients increased to a mean of 5.46% of normal levels after adjusting for muscle content. Without adjusting for muscle content, dystrophin levels were 2.87% of normal, which, according to Dyne, is about 10 times higher than levels achieved with exon 51-skipping therapy available in the U.S.
Although DELIVER wasn’t designed to detect statistically meaningful effects on clinical outcomes, available data were positive, indicating trends toward improvement relative to the placebo in measures of walking ability, upper limb strength, and lung function. Long-term data from patients who participated in the first part of DELIVER and are continuing treatment in an open-label extension have also shown “sustained functional improvement” after up to two years on the therapy, according to Dyne.
“The data from all 86 participants of the DELIVER trial will form the basis for our planned U.S. Accelerated Approval submission,” said Doug Kerr, MD, PhD, chief medical officer of Dyne. “I believe that the clinical results from DELIVER, taken together, are unprecedented in terms of the breadth, magnitude and duration of effect, and this was only possible with the participation of and partnership with the Duchenne community.”
DYNE-251 was generally tolerated well in the study. The most common side effects were fever and headache, and no serious side effects related to the treatment were documented in the registrational expansion cohort. Two participants in the open-label extension experienced malaise and/or fever that were deemed serious adverse events related to treatment. Both patients fully recovered and continued their therapy.
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