General Information

Viltepso (viltolarsen) is an antisense oligonucleotide.

Viltepso is specifically indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.

Viltepso is supplied as an injection for intravenous administration. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting Viltepso. Consider measurement of glomerular filtration rate prior to initiation of Viltepso. Monitoring for kidney toxicity during treatment is recommended. The recommended dosage of Viltepso is 80 mg/kg administered once weekly as a 60-minute intravenous infusion. If a dose of Viltepso is missed, it should be administered as soon as possible after the scheduled dose time.

Mechanism of Action

Viltepso (viltolarsen) is an antisense oligonucleotide. Viltepso is designed to bind to exon 53 of dystrophin pre-mRNA resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Exon 53 skipping is intended to allow for production of an internally truncated dystrophin protein in patients with genetic mutations that are amenable to exon 53 skipping.

Side Effects

Adverse effects associated with the use of Viltepso may include, but are not limited to, the following:

• upper respiratory tract infection
• injection site reaction
• cough
• pyrexia

Clinical Trial Results

Viltepso was approved by the FDA under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with Viltepso. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The effect of Viltepso on dystrophin production was evaluated in one study in DMD patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. Study 1 was a multicenter, 2-period, dose-finding study conducted in the United States and Canada. During the initial period (first 4 weeks) of Study 1, patients were randomized (double blind) to Viltepso or placebo. All patients then received 20 weeks of open-label Viltepso 40 mg/kg once weekly (0.5 times the recommended dosage) (N=8) or 80 mg/kg once weekly (N=8). Study 1 enrolled ambulatory male patients 4 years to less than 10 years of age (median age 7 years) on a stable corticosteroid regimen for at least 3 months. Efficacy was assessed based on change from baseline in dystrophin protein level (measured as % of the dystrophin level in healthy subjects, i.e., % of normal) at Week 25. Muscle biopsies (left or right biceps brachii) were collected from patients at baseline and following 24 weeks of Viltepso treatment, and analyzed for dystrophin protein level by Western blot normalized to myosin heavy chain (primary endpoint) and mass spectrometry (secondary endpoint). In patients who received Viltepso 80 mg/kg once weekly, mean dystrophin levels increased from 0.6% (SD 0.8) of normal at baseline to 5.9% (SD 4.5) of normal by Week 25, with a mean change in dystrophin of 5.3% (SD 4.5) of normal levels (p=0.01) as assessed by validated Western blot (normalized to myosin heavy chain); the median change from baseline was 3.8%. All patients demonstrated an increase in dystrophin levels over their baseline values. As assessed by mass spectrometry (normalized to filamin C), mean dystrophin levels increased from 0.6% (SD 0.2) of normal at baseline to 4.2% (SD 3.7) of normal by Week 25, with a mean change in dystrophin of 3.7% (SD 3.8) of normal levels; the median change from baseline was 1.9%.