Pulmonary and motor function in ambulatory and non-ambulatory participants with Duchenne muscular dystrophy treated with viltolarsen


Clinical Trials

Poster Number: M148


Amy D. Harper, MD, Children’s Hospital of Richmond at Virginia Commonwealth University, Richmond, VA, USA, Michelle L. Previtera, PhD, NS Pharma, Inc., Paramus, NJ, USA, Robert A. Crozier, PhD, NS Pharma, Inc., Paramus, NJ, USA, Leslie Magnus, MD, NS Pharma, Inc., Paramus, NJ, USA, Paula Clemens, MD, University of Pittsburgh

Background: Decline in pulmonary function is a concern for patients with Duchenne muscular dystrophy (DMD). Viltolarsen is indicated for the treatment of DMD in patients with dystrophin mutations that are amenable to exon 53 skipping. In previous studies, viltolarsen increased dystrophin levels, stabilized motor function over 4 years, and was well-tolerated. Pulmonary function was not evaluated in a viltolarsen study previously. Here we evaluated forced vital capacity (FVC), a well-established measurement of respiratory status.

Methods: This Phase 2, 48-week study evaluated safety and motor and pulmonary function in ambulant and non-ambulant participants with DMD aged ≥8 years treated with viltolarsen 80 mg/kg/week (NCT04956289). Percent predicted FVC (FVC%p), which accounts for age and height, in viltolarsen-treated participants was compared with standard of care-treated participants from the CINRG Duchenne Natural History Study (DNHS cohort), which was matched for age and ambulatory, pulmonary, and steroid status.

Results: The mean age of viltolarsen-treated participants was 12.8 ± 5.47 years (range 8─26); 50% were non-ambulatory. The mean age of the DNHS cohort was 12.7 ± 4.05 years (range, 8─21); 48% were non-ambulatory. In the safety population (n = 20), 19% of viltolarsen-treated participants reported a treatment-emergent adverse event; 4 events were assessed as drug-related. No serious adverse events or deaths were reported. No participants discontinued. Mean change from baseline in FVC%p for viltolarsen-treated participants (n = 20; 5.15 ± 2.3) was significantly improved at Week 49 compared to DNHS cohort (n = 48; −0.93 ± 1.5; p = 0.03). Performance of Upper Limb 2.0 was stable over the treatment period.

Conclusions: Safety of viltolarsen treatment is consistent with previous clinical trials. This is the first study of viltolarsen evaluating pulmonary function and it includes both ambulant and non-ambulant participants. The data suggest that viltolarsen may have beneficial effects on FVC%p. Viltolarsen can be considered an important part of the treatment strategy for patients with DMD amenable to exon 53 skipping therapy.