Surfing on new Duchenne data, Wave charges $175m offering

Phase 2 results with Wave Life Sciences' Duchenne muscular dystrophy candidate WVE-N531 pushed the company's share price to its highest level in a year and could lead to discussions with regulators about a route to market.

The results of the FORWARD-53 showed that WVE-N531 – an exon 53 skipping agent in the same general class as NPS Pharma's Viltepso (viltolarsen) and Sarepta's Vyondys 53 – was able to achieve an average dystrophin expression of 9% of normal when adjusted for muscle content, or 5.5% of normal dystrophin if unadjusted, after 24 weeks of treatment.

The improvement in dystrophin was approximately in line with the 5.9% unadjusted improvement seen with Viltepso in a phase 2 study that supported its 2020 approval by the FDA.

Shares in Wave rose 53% after the trial data was announced, taking its market cap above the $1 billion threshold. The company has moved swiftly ahead with a public offering, seeking to raise an estimated $175 million as it moves towards possible commercialisation of WVE-N531.

The 9% adjusted figure reflects the ability of the drug to penetrate into muscle tissue at high concentrations, said Wave in a letter to the DMD patient community, which reads: "Dystrophin was produced consistently across the boys, with the majority above 5% when adjusted for muscle content."

The DMD gene is made up of 79 exons, and mutations in that code can result in a dystrophin deficiency, which is responsible for the muscle wasting in DMD. Exon-skipping drugs are used to patch the mutations and allow the gene to produce partially functional dystrophin. Exon 53 mutations account for around 8% of the total DMD population.

FORWARD-53 also revealed signs of improved muscle health in DMD patients, including increases in muscle fibre size and diameter.

"We are encouraged by [this] data and plan to complete the study through 12 months (48 weeks) to allow us to learn more, including the effect of WVE-N531 on functional outcomes," said the company.

"We also plan to meet with regulators to discuss the next steps for WVE-N531 and look forward to sharing a programme update in the first quarter of 2025." It is hoping for a green light to file for accelerated approval based on the phase 2 data, which in principle would require a confirmatory trial to allow the drug to stay on the market long-term.

The future of Viltepso in the US market was thrown into doubt earlier this year after the drug missed its primary objective in the confirmatory RACER53 trial, unable to distinguish itself from placebo on functional measures – specifically, the time taken for DMD patients to stand up from a supine position.

At the time, NS Pharma – the US arm of Japanese drugmaker Nippon Shinyaku – said that additional analyses were being undertaken to see if other factors like steroid use had confounded the result and suggested the totality of evidence for Viltepso's benefit should allow it to stay on the market.

Sales of Viltepso were around $90 million last year, while Vyondys 53 brought in around $130 million. Wave has so far tested its exon-skipping therapy as a two-weekly infusion – the same as Viltepso – but has suggested it could be effective when dosed once a month, which will be tested as the trial continues. Vyondys 53 is given weekly.

It's worth noting that, in time, exon-skipping therapies could become superseded by a new generation of gene therapies for DMD, led by Sarepta's Elevidys (delandistrogene moxeparvovec), which has been cleared by the FDA for use in ambulatory and non-ambulatory DMD patients aged four and above.