Abstract Details

Decline in pulmonary function is a concern for DMD patients. Viltolarsen is indicated for the treatment of DMD patients with dystrophin mutations 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 previously.

To evaluate safety, motor function, and respiratory function, including forced vital capacity (FVC) and peak expiratory flow (PEF), in participants with Duchenne muscular dystrophy (DMD) and treated with viltolarsen.

This Phase 2, 48-week study evaluated safety and motor and pulmonary function in ambulatory and nonambulatory participants with DMD aged ≥8 years treated with viltolarsen 80 mg/kg/week (NCT04956289). Percent predicted FVC (FVC%p) and percent predicted PEF (PEF%p) in viltolarsen-treated participants was compared with participants from the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (DNHS cohort), which was matched for age and ambulatory, pulmonary, and steroid status.

The mean age of viltolarsen-treated participants (N=20) was 12.8±5.47 years; 50% were nonambulatory. The mean age of the DNHS cohort (N=48) was 12.7±4.05 years; 48% were nonambulatory. In the safety population, 19 viltolarsen-treated participants reported a treatment-emergent AE; 4 events were assessed as drug-related. No serious AEs or deaths were reported. No participants discontinued. Mean change from baseline in FVC%p and PEF%p for viltolarsen-treated participants (5.15±2.3 and 5.0±3.7, respectively) was significantly improved at Week 49 compared to DNHS cohort (-0.93±1.5; P=0.03 and -6.0±2.4; P=0.02, respectively). Performance of Upper Limb 2.0 was stable over the treatment period.

Safety of viltolarsen treatment is consistent with previous trials. In this first study examining viltolarsen effects on pulmonary function, the data indicate a positive effect on FVC and PEF, and combined with previous motor function data, suggests an additional treatment benefit of viltolarsen for DMD patients amenable to exon 53 skipping therapy.