As it gears up to submit an approval application next year, Wave Life Sciences has presented fresh phase 2 data showing its Duchenne muscular dystrophy (DMD) therapy is up to the task.
The latest 48-week data come from the Forward-53 trial of Wave’s exon skipping oligonucleotide WVE-N531 in 11 boys with exon 53 DMD. Biopsy data from eight of the boys showed a 6.4% mean muscle content-adjusted dystrophin. The average dystrophin between week 24 and 48 was 7.8%, the company said.
Seven of these eight boys achieved greater than 5% average dystrophin between 24 and 48 weeks, with Wave having previously targeted expression levels greater than 5% as a goal earlier in the study.
WVE-N531 contains chemistry that is intended to enable high drug exposure in muscle, the tissue that is at the center of the health challenges faced by people with DMD. Wave claimed today’s data showed “significant and unprecedented improvements in multiple indicators of muscle health.” These included a 28.6% reduction in mean muscle fibrosis between weeks 24 and 48 as well as a drop in median muscle necrosis and inflammation scores from 2 to 1.
A physical assessment of 10 of the boys also showed a “statistically significant and clinically meaningful” 3.8-second improvement in how long it took them to rise from the floor. Leerink Partners analysts pointed out in a note this morning that this 3.8-second improvement is greater than the 2.7-second benefit seen one year after taking Sarepta’s DMD gene therapy Elevidys.
The 48-week data for Wave’s WVE-N531 follow a 28-week readout in September 2024 that showed 5.5% mean absolute unadjusted dystrophin in nine of the boys.
“WVE-N531’s demonstrated ability to reach both myofibers and myogenic stem cells—the regenerative muscle cells—and sustain dystrophin restoration over time is impacting muscle health in ways never before seen in DMD,” Wave CEO Paul Bolno, M.D., said in this morning’s release.
“With these transformational data and feedback from FDA in hand, we are now moving toward our first NDA filing, which puts us on the path toward becoming a commercial company,” Bolno added.
Shares in Wave were up 19% in premarket trading March 26, rising to $11.23 from a Tuesday closing price of $9.44.
Wave is planning to seek permission to test DMD treatments for other exons beyond exon 53. In their note, Leerink analysts pointed out that exon 53 “appears easier to skip, but dystrophin expression seems harder.”
“So this data looks impressive to us and de-risks other exons where Wave may see even greater expression,” the analysts concluded.