Wave Life Sciences has met its goal in a Duchenne muscular dystrophy (DMD) study, positioning it to talk to regulators about accelerated approval while continuing to track patients through to the completion of the trial.
The biotech reported 5.5% mean absolute unadjusted dystrophin in its analysis of nine ambulatory boys with exon 53 DMD after 24 weeks of treatment. Wave was targeting expression levels greater than 5% going into the readout. The 5.5% figure is derived from an analysis that excluded one non-ambulatory patient who had much lower levels of dystrophin after receiving Wave’s oligonucleotide WVE-N531.
Wave’s result is in line with the data that supported accelerated approval of NS Pharma’s exon 53 DMD drug Viltepso. NS Pharma reported (PDF) mean dystrophin levels of 5.9% of normal by Week 25, which represented a 5.3% increase over baseline. However, the mean result in NS Pharma’s eight-patient study was driven by two outliers.
Two patients had dystrophin levels above 10% of normal. One other patient topped 5%. Levels were below 4.1% in the five other patients, with three people expressing less than 3.1%. Wave saw levels of dystrophin exceed 5% of normal in six patients. Levels in three of the other patients ranged from 3.3% to 4.8%. Expression in the other, non-ambulatory Wave patient was 1% of normal.
Wave also shared absolute muscle content adjusted dystrophin. 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 reported mean muscle content-adjusted dystrophin expression of 9%.
Again, the result reflected consistent performance across patients. Expression was 1.2% in the outlier at the bottom end of the range. Levels ranged from 6% to 13.9% in eight of the remaining patients. Only one ambulatory patient had an expression level—4.6%—below the 5% threshold targeted by Wave.
The biotech generated the results in a trial that administered WVE-N531 every two weeks, the same schedule as Viltepso. Wave believes its data support monthly dosing, though. Patients had “a tremendous amount of drug in the muscle with a 61-day half life,” Wave CEO Paul Bolno, M.D., said on a call with analysts to discuss the data. If the oligonucleotide is there, the muscle should produce the protein.
“Not only will we not lose efficacy, but we will continue to preserve that dynamic range of production of dystrophin,” Bolno said. “We know [monthly dosing] is a necessity for families and boys. We recognize the burden of having to go in for a weekly IV infusion.”
Wave is switching patients in the trial to monthly dosing. The biotech expects to report 48-week data in the first quarter of 2025. Feedback from regulators on a pathway to accelerated approval is due around the same time.
Shares in Wave opened up 39% at $7.40 on Tuesday morning.