Objective:

This systematic review and meta-analysis assesses its efficacy in dystrophin restoration and overall safety to guide treatment strategies.

Background:

Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle degeneration due to dystrophin deficiency. While glucocorticoids provide symptomatic relief, they do not restore dystrophin. Viltolarsen, an exon 53 skipping therapy, is under clinical evaluation. 

Design/Methods:

We systematically reviewed RCTs and observational studies from PubMed, Scopus, Web of Science, Embase, and Cochrane (up to April 2025) to evaluate viltolarsen in Duchenne muscular dystrophy. A random-effects meta-analysis was conducted, assessing adverse events through odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs).

Results:

The meta-analysis comparing viltolarsen 80 mg versus 40 mg showed no statistically significant difference in dystrophin protein levels measured by Western blot (MD: 0.65, 95% CI: -4.23 to 5.53, p = 0.79).Regarding safety, the incidence of nasopharyngitis (OR: 1.60, 95% CI: 0.69 to 3.69, p = 0.27) and rash (OR: 1.67, 95% CI: 0.50 to 5.61, p = 0.41) did not significantly differ between the two doses.

These findings suggest that while both doses are well tolerated, no clear dose-dependent advantage was observed in dystrophin restoration.

Conclusions:

Viltolarsen, at both 40 mg and 80 mg doses, demonstrated a favorable safety profile in Duchenne muscular dystrophy (DMD) without a significant increase in adverse events. However, its impact on dystrophin restoration remains inconclusive, with no clear dose-dependent advantage. Larger studies with extended follow-up are essential to determine its long-term efficacy and optimal dosing strategy.