Dive Brief:

• Wave Life Sciences is preparing to seek Food and Drug Administration approval of its therapy for Duchenne muscular dystrophy after claiming success in a Phase 2 study.
• After discussions with FDA officials, the company now plans to file an application next year seeking accelerated approval of WVE-N531, with potential monthly dosing, Wave said Wednesday. The company’s shares rose by about 5% in early trading.
• Although small, the Phase 2 trial showed that a so-called exon-skipping therapy can result in “substantial improvements” in muscle health, Wave said. WVE-N531 led to increased expression of dystrophin, a critical muscle protein that is either lacking or defective in Duchenne patients.

Dive Insight:

Exons are specific segments of the genetic code that encode proteins. Mutations can disrupt the process and cancel the production of the protein. Duchenne therapies like WVE-N531 aim to bypass a specific mutated exon — in this case exon 53 — in order to get production of dystrophin protein, in slightly different form, back on track.

The new data suggest WVE-N531 could be a “best-in-class” option for the roughly 8% to 10% of Duchenne patients with a genetic mutation that makes them amenable to exon 53 skipping, Jefferies analyst Roger Song wrote in a note to clients. The study’s finding that the treatment was safe and well-tolerated through 48 weeks is also key, he said.

Currently, there are two FDA-approved treatments that target exon 53: Sarepta’s Vyondys 53 and NS Pharma’s Viltepso. Both won approval based on their effects on dystrophin production — clearances contingent on follow-up studies confirming their clinical benefits for patients. NS Pharma’s initial confirmatory research failed last year, though the drug remains on the market. Sarepta’s trial is ongoing.

Wave’s Phase 2 study, known as Forward-53, only included 11 patients and compared functional test results against historical data, so it’s not the typical placebo-controlled large study that the FDA relies on to clear major therapies. But in the case of rare diseases like Duchenne, the agency allows other paths to approval.

In recent discussions, FDA officials confirmed companies can still use dystrophin expression to serve as a surrogate endpoint and win accelerated approval, Wave said Wednesday. The company also touted the functional results it saw — including a statistically significant improvement versus historical controls in “time to rise.” However, the difference between groups in a test of motor skills called the North Star Ambulatory Assessment was not significant.

The company plans to keep sharing data from Forward-53 and additional research that would support monthly dosing. It also plans to engage the FDA in a planned confirmatory trial, Wave said.