Key takeaways:

• Viltolarsen preserved muscle function over 2 years and delayed progression of Duchenne muscular dystrophy over 4 years.
• Viltolarsen was well-tolerated, with most adverse events being mild or moderate.

Viltolarsen delayed disease progression over 4 years in children with Duchenne muscular dystrophy, with most treatment-emergent adverse events being mild or moderate, according to a poster at the 2023 MDA Clinical & Scientific Conference.

“Viltolarsen is an antisense oligonucleotide designed to treat Duchenne muscular dystrophy in patients with a confirmed mutation of the Duchenne muscular dystrophy gene amenable to exon 53 skipping,” Edward C. Smith, MD, professor of pediatrics and associate professor of neurology in the department of pediatrics at Duke University School of Medicine, and colleagues wrote. “In an initial North American phase 2 study, treatment with viltolarsen in participants with Duchenne muscular dystrophy amenable to exon 53 skipping resulted in significant increases in dystrophin production at a weekly dose of 80 mg/kg, as assessed by western blot after 24 weeks of treatment.”

The researchers evaluated outcomes in 16 boys with Duchenne muscular dystrophy, aged 4 to 10 years, who participated in a 24-week trial of viltolarsen and a 192-week extension study. In total, participants were assigned 1:1 to receive a weekly infusion of 40 mg/kg viltolarsen or 80 mg/kg viltolarsen for 4 years.

Efficacy outcomes in the study group were compared with those from the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS), which served as a control group.

Compared with controls, participants taking viltolarsen maintained motor function over the first 2 years of treatment from baseline, while those in the CINRG DNHS performed worse during that period. Starting at week 73 during the extension period, time to stand from supine position and velocity were significantly different between participants taking viltolarsen and controls.

Additionally, time to climb four stairs was similar or better among the viltolarsen group compared with controls across the study period.

Safety analyses revealed that all 16 viltolarsen participants experienced a treatment-emergent adverse event, the most common of which were cough (63%) and nasopharyngitis (56%).

Researchers reported four serious adverse events, none of which were related to viltolarsen. There were no deaths or discontinuation of treatment.

“The study outcome of better motor function vs. historical controls, and a favorable safety profile, have been demonstrated in this trial, the longest exon 53 skipping trial to date,” Smith and colleagues wrote. “Viltolarsen can be considered as an important part of the treatment strategy for patients with Duchenne muscular dystrophy who are amenable to exon 53 skipping.”