NEW YORK – Wave Life Sciences on Wednesday said it intends to file a new drug application (NDA) next year seeking accelerated approval for WVE-N531 as a treatment for some patients with Duchenne muscular dystrophy based on feedback from the US Food and Drug Administration and positive 48-week data from its Phase II FORWARD-53 trial.
The Cambridge, Massachusetts-based biotech said it recently met with the FDA to discuss interim 24-week data and initial plans for a confirmatory trial. During the meeting, the agency confirmed that the accelerated approval pathway, using dystrophin expression as a surrogate endpoint, remains an option for the company.
In its NDA, Wave plans to submit data from the FORWARD-53 study, including evidence to support monthly dosing. The firm said it will continue to work with the FDA as it plans a global confirmatory trial for WVE-N531.
"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," Wave President and CEO Paul Bolno said in a statement. "We expect WVE-N531 to become the first-line treatment of choice for boys amenable to exon 53 skipping."
WVE-N531 is an exon-skipping oligonucleotide that Wave is investigating as a treatment for boys with Duchenne with genetic mutations that are amenable to exon 53 skipping. Duchenne is caused by mutations in the DMD gene that result in patients having abnormal or deficient amounts of the protein encoded by DMD, dystrophin.
In the open-label FORWARD-53 trial, investigators enrolled 11 patients between 5 and 11 years old, 10 of whom were ambulatory. Patients received the drug biweekly for 48 weeks. The 11 participants have advanced to the extension portion of the study, in which they will receive monthly doses of WVE-N531.
The study met all endpoints, including showing that WVE-N531 sustained exon skipping, reversed muscle fibrosis, and restored dystrophin in participants through 48 weeks of treatment. Investigators also observed functional improvements, with patients experiencing a 3.8 second improvement in time-to-rise tests compared to natural history.
Wave said it is accelerating programs for multiple Duchenne candidates targeting other DMD exons, such as exons 52, 51, 45, and 44, and expects to file clinical trial applications for some of these candidates next year. The company said that, collectively, these exon skipping programs and WVE-N531 could treat an estimated 40 percent of Duchenne cases.