Viltolarsen

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.

• VILTEPSO is 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. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VILTEPSO [see Clinical Studies ( 14 )].

• None.contraindicated

Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting VILTEPSO. ( 2.1 ) Recommended dosage is 80 milligrams per kilogram of body weight once weekly. ( 2.2 ) Administer as an intravenous infusion over 60 minutes. ( 2.2 , 2.4 ) If the volume of VILTEPSO required is less than 100 mL, dilution in 0.9% Sodium Chloride Injection, USP, is required. ( 2.3 ) 2.1 Monitoring to Assess Safety 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. Obtain the urine samples prior to infusion of VILTEPSO or at least 48 hours after the most recent infusion [see Warnings and Precautions ( 5.1 )]. 2.2 Dosing Information 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. 2.3 Preparation Instructions Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Prepare the VILTEPSO dose using aseptic technique. Calculate the total dose of VILTEPSO to be administered based on the patient's weight and the recommended dosage of 80 mg/kg. Determine the volume of VILTEPSO needed and the correct number of vials to supply the full calculated dose.

Kidney Toxicity: Based on animal data, may cause kidney toxicity. Kidney function should be monitored; creatinine may not be a reliable measure of renal function in DMD patients. ( 5.1 , 13.2) 5.1 Kidney Toxicity Kidney toxicity was observed in animals who received viltolarsen [see Use in Specific Populations ( 8.4 )]. Although kidney toxicity was not observed in the clinical studies with VILTEPSO, the clinical experience with VILTEPSO is limited, and kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Kidney function should be monitored in patients taking VILTEPSO. Because of the effect of reduced skeletal muscle mass on creatinine measurements, serum creatinine may not be a reliable measure of kidney function in DMD patients. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting VILTEPSO. Consider also measuring glomerular filtration rate using an exogenous filtration marker before starting VILTEPSO. During treatment, monitor urine dipstick every month, and serum cystatin C and urine protein-to-creatinine ratio every three months. Only urine expected to be free of excreted VILTEPSO should be used for monitoring of urine protein. Urine obtained on the day of VILTEPSO infusion prior to the infusion, or urine obtained at least 48 hours after the most recent infusion, may be used.

The most common adverse reactions (incidence ≥15% in patients treated with VILTEPSO) were upper respiratory tract infection, injection site reaction, cough, and pyrexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact NS Pharma at 1-866 NSPHARM (1-866-677-4276) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials with VILTEPSO, 32 patients have been exposed to VILTEPSO once weekly, ranging between 40 mg/kg (0.5 times the recommended dosage) and 80 mg/kg (the recommended dosage), including 16 patients treated for greater than 12 months and 8 patients treated for greater than 24 months as part of an ongoing open-label extension study. All patients were male and had genetically confirmed DMD. Study 1 was a multicenter, 2-period, dose-finding study conducted in the United States and Canada in males 4 years to less than 10 years of age on a stable corticosteroid regimen for at least 3 months. 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 VILTEPSO 40 mg/kg once weekly (0.5 times the recommended dose) (N=8), or 80 mg/kg once weekly (N=8) [see Clinical Studies ( 14 )].

8.1 Pregnancy Risk Summary There are no human or animal data available to assess the use of VILTEPSO during pregnancy. In the U.S. general population, major birth defects occur in 2 to 4%, and miscarriage occurs in 15 to 20% of clinically recognized pregnancies. 8.2 Lactation Risk Summary There are no human or animal data to assess the effect of VILTEPSO on milk production, the presence of viltolarsen in milk, or the effects of VILTEPSO on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for VILTEPSO and any potential adverse effects on the breastfed infant from VILTEPSO or from the underlying maternal condition. 8.4 Pediatric Use VILTEPSO is indicated for the treatment of DMD in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping, including pediatric patients [see Clinical Studies ( 14 )]. Juvenile Animal Toxicity Data Viltolarsen (0, 15, 60, 240, or 1200 mg/kg) was administered to juvenile male mice by subcutaneous injection on postnatal day (PND) 7 and by intravenous injection weekly from PND 14 to PND 70. The highest dose resulted in deaths because of renal toxicity.

Metabolism

The pharmacokinetics of viltolarsen was evaluated in DMD patients following administration of intravenous (IV) doses ranging from 1.25 mg/kg/week (0.016 times the recommended dosage) to 80 mg/kg/week (the recommended dosage). Viltolarsen exposure increased proportionally with dose, with minimal accumulation with once-weekly dosing.

• Aug 12, 2020NDANDA212154Nippon Shinyaku

1. 1Pyrexia1912%
2. 2Illness106.5%
3. 3Vomiting106.5%
4. 4Pneumonia85.2%
5. 5Malaise74.5%
6. 6Weight Increased74.5%
7. 7Covid-1963.9%
8. 8Cough53.2%
9. 9Fall53.2%
10. 10Product Dose Omission Issue53.2%
11. 11Sars-cov-2 Test Positive53.2%
12. 12Diarrhoea42.6%
13. 13Nausea42.6%
14. 14Off Label Use42.6%
15. 15Upper Respiratory Tract Infection42.6%

The 5 most recently updated of 5 ClinicalTrials.gov registrations naming Viltolarsen as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study to Assess the Efficacy and Safety of Viltolarsen in Ambulant Boys With DMD (RACER53)
  Completed · Phase 3 · Interventional · 77 enrolled · NS Pharma, Inc.
  NCT04060199updated 2024-12-11
• Study to Assess the Safety, Tolerability, and Efficacy of Viltolarsen in Ambulant and Non-Ambulant Boys With DMD (Galactic53)
  Completed · Phase 2 · Interventional · 20 enrolled · NS Pharma, Inc.
  NCT04956289updated 2024-08-20
• Study to Assess the Safety and Efficacy of Viltolarsen in Ambulant Boys With DMD (RACER53-X)
  Unknown · Phase 3 · Interventional · 74 enrolled · NS Pharma, Inc.
  NCT04768062updated 2024-02-14
• Long-term Use of Viltolarsen in Boys With Duchenne Muscular Dystrophy in Clinical Practice (VILT-502)
  Active not recruiting · Phase 4 · Interventional · 9 enrolled · NS Pharma, Inc.
  NCT04687020updated 2022-10-19
• The Expanded Access Use of Viltolarsen in Duchenne Muscular Dystrophy With Confirmed Exon 53 Amenable Mutation
  Approved for marketing · Expanded access · NS Pharma, Inc.
  NCT04337112updated 2020-08-18

Frequently asked questions

How does Viltolarsen work?

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.

What is Viltolarsen used for?

According to FDA labeling, Viltolarsen carries indications including: VILTEPSO is 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. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VILTEPSO [see Clinical Studies ( 14 )].. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Viltolarsen?

Viltolarsen is classified as Other drugs for disorders of the musculo-skeletal system, Gene Alterations, Gene Transcription Modulation, Unknown Physiological Effect.

What are the brand names for Viltolarsen?

Viltolarsen is marketed under brand names including Viltepso.

What are the contraindications for Viltolarsen?

Viltolarsen labeling lists contraindications including: None.. Always consult the full prescribing information and a clinician.