Nippon Shinyaku’s DMD Drug Fails Confirmatory Trial

The future of Nippon Shinyaku’s Duchenne muscular dystrophy (DMD) therapy, Viltepso, has been thrown into doubt after it failed a clinical trial designed to upgrade its 2020 accelerated approval. The Japanese group’s NS Pharma subsidiary revealed that Viltepso (viltolarsen) missed its primary objective in the confirmatory RACER53 trial, and was unable to distinguish itself from placebo in the time taken for DMD patients to stand up from a supine position.

Viltepso was approved by the FDA for DMD patients with mutations in the dystrophin gene amenable to exon 53 skipping, a group that accounts for around 8% of the total DMD population. It was the second exon 53-skipping drug to reach the US market after Sarepta’s rival Vyondys 53 (golodirsen), which was controversially cleared by the FDA in 2019 after a previous rejection and an appeal from the company.

NS Pharma stated that continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The RACER53 Study compared Viltepso as an 80 mg/kg once weekly dose to placebo in 77 ambulatory boys with DMD over 48 weeks. There was a trend towards an increase in time to stand from supine (TSS) with NS Pharma’s drug, but the placebo group showed a similar trend, making it impossible to show a significant difference, according to the company.

NS Pharma’s president, Tsugio Tanaka, said additional analyses are being undertaken to see if other factors confounded the result, such as age, treatment period, and use of concomitant drugs like corticosteroids. Considering the results of prior clinical studies, we have confidence that viltolarsen can be a beneficial treatment for amenable patients with Duchenne, he asserted.

Sales of Viltepso were around $90 million last year, while Sarepta’s Vyondys 53 and other exon-skipping DMD therapies Exondys 51 (eteplirsen) and Amondys 45 (casimersen) collectively brought in around $950 million. Vyondys 53 contributed $130 million of that total.

Exon-skipping therapies could, however, become superseded by a new generation of gene therapies for DMD, led by Sarepta’s Elevidys (delandistrogene moxeparvovec), which was cleared by the FDA for ambulatory patients aged four to five in the middle of 2023 and had generated $200 million in sales by year-end, of which $131 million came in the fourth quarter. Sarepta recently filed for approval to extend the label for Elevidys to include all ambulatory DMD patients, despite missing its primary objective in a phase 3 trial.