Dyne Therapeutics’ Duchenne muscular dystrophy (DMD) therapy z-rostudirsen significantly improved dystrophin level and function versus placebo in boys aged four to 16 years with the condition who were eligible for exon 51 skipping therapy.
The results showed an increase in dystrophin levels to 5.46% at six months after adjusting for muscle content. This amounted to an approximate seven-fold change from baseline, which was around the same increase seen in earlier trials of z-rostudirsen.
DMD is a rare, progressive neuromuscular disorder caused by a range of different mutations in the DMD gene found on the X chromosome that cause loss of functional dystrophin protein. Around 12,000 individuals in the U.S. are affected by the condition and up to 2,200 of these are eligible for exon 51 skipping medication.
Exon skipping medicines are short antisense oligonucleotides that bind to a chosen coding section in the DMD gene’s pre‑mRNA, in this case exon 51. They cover up that section so the cell leaves it out when it builds the final protein, which changes a broken Duchenne mutation into a readable one that can make a shorter but still partly working dystrophin protein.
Several are already approved by the FDA including eteplirsen, which also skips exon 51, golodirsen and viltolarsen, skipping exon 53, and casimersen, skipping exon 45.
The Phase I/II Deliver trial included 32 boys with DMD and different degrees of walking ability. Of these, 24 received 20 mg/kg z-rostudirsen every four weeks and eight were assigned to a placebo group.
Not accounting for muscle content, boys treated with z-rostudirsen had an increase in dystrophin levels to 2.87% of normal level, which is around 10 times higher than the increase seen in boys with DMD treated with eteplirsen.
In addition to achieving higher levels of dystrophin in patients than eteplirsen, another advantage of z-rostudirsen is that it can be dosed less frequently and has a good safety profile.
“With its high level of dystrophin expression, favorable safety profile, convenient monthly dosing regimen, and functional improvement as assessed by six prespecified clinical measures, z-rostudirsen has the potential to transform the care of those living with DMD amenable to exon 51 skipping,” said John Cox, president and chief executive officer of Dyne, in a press statement.
“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.”
