RARE Daily

NS Pharma’s Viltepso Fails Confirmatory Trial in Duchenne Muscular Dystrophy

May 28, 2024

Rare Daily Staff

NS Pharma, a subsidiary of Nippon Shinyaku, said preliminary analysis showed its Duchenne muscular dystrophy drug Viltepso failed the primary endpoint in a global late-stage trial in patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping.

Duchenne muscular dystrophy is a progressive form of muscular dystrophy that occurs primarily in males. It causes progressive weakness and loss of skeletal, cardiac, and respiratory muscles. Early signs of Duchenne may include delayed ability to sit, stand or walk. There is a progressive loss of mobility, and by adolescence, patients with Duchenne may require the use of a wheelchair. Cardiac and respiratory muscle problems begin in the teenage years and lead to serious, life-threatening complications.

Viltepso, an antisense oligonucleotide, was approved by the U.S. Food and Drug Administration in 2020 under the FDA accelerated approval pathway based on an increase in dystrophin production in skeletal muscle observed in treated patients. In the United States, continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The global phase 3 RACER53 Study is a randomized, double-blind, placebo-controlled, comparative study of 77 ambulatory boys with Duchenne. The study evaluated the efficacy and safety of an 80 mg/kg once weekly dosing of the treatment—versus placebo—for 48 weeks and was intended to serve as a confirmatory study.

The primary endpoint of the study was time to stand from supine evaluated as velocity (rise/sec). The viltolarsen group showed a trend of increased velocity from baseline after treatment for 48 weeks. However, the placebo group also showed a trend of increased velocity, and there was no statistically significant difference between the viltolarsen group and the placebo group.

Preliminary safety results indicated that all adverse events that occurred under viltolarsen treatment were mild or moderate. There were no treatment emergent adverse events that led to discontinuation of the drug during the study.

“We are currently conducting further detailed data analyses and identifying factors that may have influenced the results, such as age, treatment period, and effect of concomitant drugs including glucocorticoid therapy,” said NS Pharma President Tsugio Tanaka. “Considering the results of prior clinical studies, we have confidence that viltolarsen can be a beneficial treatment for amenable patients with Duchenne.”

Specifically, in addition to the increase in dystrophin production in skeletal muscle that formed the basis of the FDA approval, a previously reported phase 2, open-label, long-term extension study evaluated viltolarsen in 16 subjects between the ages of four and 10 with Duchenne amenable to exon 53 skipping. The study found that subjects receiving viltolarsen showed statistically significant improvements in the study’s primary endpoint of mean change from baseline for Time to Stand at week 205 as compared to a historical control group that was matched for key factors. In this study, treatment emergent adverse events were primarily mild or moderate. No study participants discontinued the study drug due to adverse events.

NS Pharma is currently conducting further detailed data analyses, including post-hoc data analyses, and plans to work closely with regulatory authorities to determine how to proceed based on the results of this analysis and in the best interests of patients. The company will report on additional analyses and discussions with the regulatory authorities at a later date.

Prior to its approval in the U.S. in August 2020, Viltepso was granted Priority Review as well as Rare Pediatric Disease, Orphan Drug and Fast Track designations. Viltepso is also approved in Japan under the Sakigake designation, orphan drug designation, and designation of Conditional Early Approval System.


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