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DENVER -- Viltolarsen (Viltepso) was well tolerated by boys and men with Duchenne muscular dystrophy (DMD), with no new safety signals, according to results from the open-label, phase II trial.

The results also suggested a clinical benefit in pulmonary function with the exon-skipping therapy, as measured by percent predicted forced vital capacity (FVC%p) and peak cough flow (PCF), Michelle Previtera, PhD, associate director for medical affairs at NS Pharma, and colleagues reported during a late-breaking poster session at the American Academy of Neurology annual meeting.

Among ambulatory participants on viltolarsen, 90% showed an increase or stabilization in FVC%p from baseline, with a significant overall change at week 49 (least squares mean change 8.3%, P=0.02). Among nonambulatory patients, FVC%p increased for participants receiving viltolarsen, and decreased for the control group (least squares mean change 1.6% vs -3.2%, respectively).

"This is the first data on pulmonary function, so this was really encouraging to see in both the ambulatory and the nonambulatory population, because we haven't studied [it] in the nonambulatory population," Previtera told 名媛直播.

"Combined with previous motor function data, these results suggest an additional treatment benefit of viltolarsen for patients with DMD amenable to exon 53-skipping therapy," Previtera and colleagues reported in the poster.

Duchenne muscular dystrophy is incurable, occurring mostly in boys and caused by mutations in the dystrophin gene, leading to a loss of functional dystrophin and muscle damage. As patients lose muscle strength, pulmonary function is impacted, eventually resulting in assisted ventilation.

Exon-skipping therapies like viltolarsen can cause parts of the mutated gene to be skipped, yielding shortened usable dystrophin, according to Previtera and colleagues. The FDA granted viltolarsen accelerated approval status in 2020, and a confirmatory is ongoing to assess clinical benefit for the drug in DMD patients with a confirmed dystrophin gene mutation amenable to exon 53 skipping.

The FDA granted accelerated approval to another exon 53-skipping therapy, golodirsen (Vyondys 53), . The first exon-skipping treatment granted accelerated approval in DMD was eteplirsen (Exondys 51) . Both of those products are made by Sarepta Therapeutics, which also received accelerated approval for another exon-skipping therapy, casimersen (Amondys 45), .

In the latest study, the researchers compared 20 ambulatory and nonambulatory males taking 80 mg/kg of viltolarsen intravenously once weekly to a control group of 48 males from the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS), matched for age and ambulatory and steroid status, among other baseline characteristics. Ambulatory males were about 10 years old, and non-ambulatory males were nearly 16.

Nearly all participants on viltolarsen (19 out of 20) experienced mild-to-moderate treatment-emergent adverse events (TEAEs), and four events were considered treatment-related. There were no serious adverse events, discontinuations due to TEAEs, or deaths.

Previtera and colleagues also measured an exploratory endpoint, PCF, in liters per minute (L/min). For ambulatory patients, the mean PCF change from baseline was larger in those on viltolarsen than CINRG DNHS controls. For nonambulatory patients, those on viltolarsen showed a significant mean change from baseline compared to the control group at week 49 (56.7 L/min higher, P=0.01).

In both ambulatory and nonambulatory patients receiving viltolarsen, total and midlevel elbow scores on the measurement remained stable over 49 weeks.

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