Nine years after Sarepta Therapeutics’ Exondys 51 won a controversial FDA approval to treat a subset of patients with Duchenne muscular dystrophy (DMD), challenger from Massachusetts biotech Dyne Therapeutics is moving toward a regulatory filing on the heels of a trial win.
Dyne’s phase 1/2 Deliver study enrolled 86 patients with DMD amenable to 51 skipping, who make up about 13% of the overall DMD patient population, according to a Dec. 8 company presentation.
In the registrational expansion cohort of the study, which comprised 32 patients, patients treated with 20 mg/kg of z-rostudirsen every four weeks experienced a statistically significant change from baseline in muscle-content adjusted dystrophin expression, the biotech said in a press release. In the group, 24 patients received the therapy and eight received placebo.
After six months, patients treated with the drug reached mean absolute dystrophin expression of 5.46% of normal levels, when adjusting for muscle content. The unadjusted number was 2.87%, the company said.
While cross-trial comparisons are imperfect for various reasons, a clinical trial of Sarepta’s Exondys 51 showed that patients who received the weekly drug reached 0.3% of normal dystrophin levels, Dyne pointed out.
As for functional endpoints, Dyne touted “improvement relative to placebo” across six measures such as time to rise, 10-meter walk/run velocity and lung function.
The drug “has the potential to transform the care of those living with DMD amenable to exon 51 skipping,” Dyne CEO John Cox said in a statement, describing the data as “unprecedented.“
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The company plans to submit an application for accelerated FDA approval in the second quarter of next year. A launch in early 2027 could follow, the CEO added. The company is eyeing a market of 1,600 individuals in the U.S. who have “significant unmet need,“ according to Cox.
Dyne further touted a “favorable” safety and tolerability profile, noting that most treatment-emergent adverse events (TEAEs) were mild or moderate. The most common TEAEs were fever and headache. No related serious TEAEs were seen in the registrational cohort, the biotech said.
Dyne isn’t waiting for a potential approval to build out its team, with Cox noting that the biotech has added medical, commercial and CMC experts “to enable a capital efficient and successful launch.”
In a note to clients Monday, Evercore ISI analyst Gavin Clark-Gartner wrote that the results meet the bar for an accelerated approval. The analyst is modeling 75% to 80% chances of approval for the product, plus $700 million in potential peak sales, mostly driven by switches from Sarepta’s rival offering.
After the data drop and an investor presentation Monday, Dyne’s shares were trading up about 15% at $23.34 apiece.
In addition to the planned regulatory interactions, Dyne says it’s looking to start a phase 3 trial next year “to support global approvals.”
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The trial readout comes right on the heels of Capricor Therapeutics’ DMD cell therapy triumph with deramiocel. Among patients enrolled in the Hope-3 trial, those given deramiocel every three months for a year experienced significantly slower deterioration in upper limb function compared to those given placebo, the biotech said last week.
Sarepta, for its part, had planned to introduce its own successor to Exondys 51 but axed a follow-up candidate last year due to a safety signal.
