According to Wave Life Sciences, the positive safety data supports moving the therapy into a Phase 2/3 trial, planned to start in 2019, to confirm the safety profile and establish efficacy. The company also expects interim efficacy data from an ongoing extension study in the second half of 2019.
“These results mark an important milestone for the Duchenne community and toward our goal of inducing meaningful, natural dystrophin expression in boys with DMD who are amenable to exon 51 skipping,” Paul Bolno, MD, president and CEO of Wave Life Sciences, said in the release.
Currently recruiting, the double-blind, placebo-controlled Phase 1 clinical trial (NCT03508947) is evaluating WVE-210201’s safety, tolerability, and plasma concentrations of ascending doses of the compound in boys with DMD, ages 5 to 18, who carry a dystrophin gene mutation amenable to exon 51 skipping. The trial is being conducted in several countries including the U.S., Canada, U.K., Belgium, France, Italy and the Netherlands.
Researchers expect to enroll up to 40 patients, including ambulatory and non-ambulatory patients, randomly assigned to either one of five doses of WVE-210201 or a placebo, all given intravenously (by injection into the vein). After completing the study, participants may opt to enroll in an open-label extension study where they will all receive WVE-210201.
Data from both the Phase 1 and extension studies will be important for the company’s request for accelerated approval to the U.S. Food and Drug Administration.
Based on the four (undisclosed) doses already tested, one has been selected to be used in the upcoming Phase 2/3 trial. The study is designed to measure clinical efficacy and dystrophin expression, and the company intends to use this data to seek regulatory approvals worldwide.
Genes, which often provide instructions to make proteins, are made up of many smaller components called exons. When even one exon is irregular (for example, due to mutation), it can lead to either a deficiency in the protein for which it provides instructions or a nonfunctional protein. DMD patients have a mutation in the DMD gene, which provides instructions for making a protein called dystrophin.
WVE-210201 is based on a type of technology called exon skipping and was developed for the 13 percent of DMD patients who have a specific type of mutation in the DMD gene that makes them amenable to exon 51 skipping treatment. The exon-skipping method allows the cellular machinery to “skip over” a particular exon — such as exon 51 — which restores the genetic sequence to some extent.
In preclinical studies with DMD patient-derived muscle cell progenitors (myoblasts), the therapy was able to restore the amount of dystrophin to about half the normal levels.
Recently, the FDA granted WVE-210201 orphan drug designation and rare pediatric disease designation for the treatment of DMD. The candidate also received orphan drug status from the European Commission.
“PPMD continues to be optimistic about the progress the team at Wave Life Sciences is making with their stereopure exon 51 skipping program for Duchenne. We are pleased to see WVE-210201 advance on the clinical development path and look forward to more updates from the Wave team,” said Pat Furlong, founding president and CEO of Parent Project Muscular Dystrophy (PPMD).