Wave Eyes Accelerated Approval with New Phase 2 DMD Data

Wave Life Sciences has announced promising new Phase 2 biomarker data for its exon-skipping therapy aimed at treating certain patients with Duchenne muscular dystrophy (DMD). The company revealed the results at the 24-week midpoint of a study that involves administering WVE-N531 every two weeks to 11 boys with DMD who are eligible for exon 53 skipping. Among these participants, ten boys can walk independently, while one is non-ambulatory.

The company reported biomarker data from nine of the ten ambulatory boys. Anne-Marie Li-Kwai-Cheung, Wave's Chief Development Officer, mentioned that they did not obtain biomarker results from one boy due to the poor quality of his muscle biopsy. The findings indicated that muscle content-adjusted dystrophin levels were 9% of normal, and the average unadjusted dystrophin expression was 5.5% of normal. Remarkably, eight out of the nine ambulatory boys achieved muscle content-adjusted dystrophin levels of at least 5% of normal, suggesting that the boys were producing more of the essential muscle protein.

CEO Paul Bolno highlighted the significance of these findings, noting that consistently achieving 9% dystrophin levels is a groundbreaking result in a field where low and inconsistent levels are common. Following this announcement, Wave’s shares surged by approximately 45%.

Furthermore, the company pointed out that WVE-N531 could penetrate muscle stem cells, a feat not previously reported with existing gene therapy or exon-skipping treatments, according to Li-Kwai-Cheung. On the market today, two exon 53 skipping therapies exist: Sarepta Therapeutics' Vyondys 53 and NS Pharma's Viltepso. In June, Sarepta also received a broad and controversial approval for its DMD gene therapy.

Patients currently using these exon-skipping therapies are dosed weekly, whereas Wave's experimental treatment in this study is administered biweekly. The company plans to transition the enrolled boys to a once-monthly dosing regimen, leveraging the drug’s 61-day half-life.

In terms of safety, four mild adverse events were reported in three boys, but no serious side effects or study discontinuations occurred. Li-Kwai-Cheung remarked that the treatment exhibited an exceptionally clean safety profile for an exon-skipping therapy.

Although Wave did not share data on functional improvements, it expects to have final 48-week results by the first quarter of 2025. At that point, the company plans to engage with US regulators to discuss the accelerated approval pathway.

Additionally, Bolno informed investors that the company is evaluating another endpoint known as stride velocity 95th centile (SV95C), a digital measurement of a patient's fastest strides over a 180-hour period. European regulators have given more importance to this measure compared to their US counterparts, using it as a secondary endpoint for DMD studies.

Bolno emphasized the importance of generating these data, stating that it would be crucial for considering treatment options not only in the US but also internationally.