Data from the Phase 2 Galactic53 clinical trial suggests that viltolarsen (Viltepso; NS Pharma), an FDA-approved exon-skipping therapy, improves respiratory and motor function in both ambulatory and nonambulatory patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping. The findings, presented at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, highlight the potential of viltolarsen in addressing key clinical challenges in DMD.
The Galactic53 trial (NCT04956289) included 20 patients aged at least 8 years old, treated with viltolarsen at 80 mg/kg/week. The study compared outcomes of these patients to a control group (n = 48) from the CINRG Duchenne Natural History Study (DNHS). The primary focus was on evaluating pulmonary and upper limb function in both ambulatory and nonambulatory DMD patients.
Pulmonary and Motor Function Improvements
According to the research led by Amy Harper, MD, percent predicted forced vital capacity (FVC%p) was significantly higher at week 49 in viltolarsen-treated patients compared to controls. Specifically, ambulatory patients (n = 10) showed an 8.3% (±3.3) increase versus 1.2% (±2.1) in controls, while nonambulatory patients (n = 10) showed a 1.6% (±3.0) increase versus -3.2% (±2.0) in controls. Additionally, peak cough flow (PCF) was higher in the viltolarsen group compared to the DNHS controls for both ambulatory and nonambulatory participants. Performance of the upper limb (PUL) 2.0 scores remained stable with viltolarsen treatment.
Safety and Tolerability
Nineteen out of the 20 viltolarsen-treated patients experienced treatment-emergent adverse events (TEAEs), with four being treatment-related. However, no serious adverse events were reported, and no participants discontinued the trial due to adverse effects.
Additional Findings from Scientific Reports
Prior to the AANEM 2024 meeting, results from the GALACTIC53 trial were published in Scientific Reports. These data indicated that 90% (9 of 10) of nonambulatory participants receiving viltolarsen had an increase or stabilization in FVC%p from baseline, and 60% (6 of 10) maintained FVC%p values greater than 50% at week 49. The least square (LS) mean change from baseline in the total North Star Ambulatory Assessment (NSAA) score for ambulatory participants in the viltolarsen group was +2.2 (SE, 0.8) points, compared with -2.5 (SE, 1.4) for the CINRG DNHS cohort.
Study Limitations and Context
The study had limitations, including a small sample size and the absence of a placebo control group. The CINRG DNHS control cohort, while useful, is less rigorous than a placebo-controlled trial. Control group matching was based on age, ambulatory status, and steroid use, but ambulatory status selection was not prespecified. Furthermore, the CINRG DNHS control data was collected between 2006 and 2016, predating the Galactic53 study by several years, though DMD care guidelines remained consistent during this period.
Viltolarsen received accelerated approval in 2020 based on Phase 2 study data. However, the Phase 3 RACER53 study (NCT04060199), designed to confirm the clinical benefit of viltolarsen, yielded mixed results. The trial, involving 77 DMD patients, showed no significant difference between viltolarsen and placebo on the primary endpoint of velocity after 48 weeks. NS Pharma is conducting further analyses to understand these results and will work with regulatory authorities to determine the best course of action.
