Casimersen

Casimersen is designed to bind to exon 45 of dystrophin pre-mRNA resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 45 skipping. Exon 45 skipping is intended to allow for production of an internally truncated dystrophin protein in patients with genetic mutations that are amenable to exon 45 skipping [see Clinical Studies ( 14 )] .

• AMONDYS 45 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 45 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45 [see Clinical Studies ( 14 )] .

• AMONDYS 45 is contraindicated in patients with known serious hypersensitivity to casimersen or to any of the inactive ingredients in AMONDYS 45. Instances of hypersensitivity, including angioedema and anaphylaxis, have occurred in patients receiving AMONDYS 45 [see Warnings and Precautions ( 5.1 )] .contraindicated

Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting AMONDYS 45 ( 2.1 ) 30 milligrams per kilogram of body weight once weekly ( 2.2 ) Administer as an intravenous (IV) infusion over 35 to 60 minutes via an in-line 0.2 micron filter ( 2.2 , 2.4 ) Dilution required prior to administration ( 2.3 ) 2.1 Monitoring to Assess Safety Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio (UPCR) should be measured before starting AMONDYS 45. Consider measurement of glomerular filtration rate prior to initiation of AMONDYS 45. Monitoring for kidney toxicity during treatment is recommended. Obtain the urine sample prior to infusion of AMONDYS 45 or at least 48 hours after infusion [see Warnings and Precautions ( 5.2 )] . 2.2 Dosing Information The recommended dosage of AMONDYS 45 is 30 milligrams per kilogram administered once weekly as a 35 to 60-minute intravenous infusion via an in-line 0.2 micron filter. If a dose of AMONDYS 45 is missed, it may be administered as soon as possible after the scheduled dose. 2.3 Preparation Instructions AMONDYS 45 is supplied in single-dose vials as a preservative-free concentrated solution that requires dilution prior to administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use aseptic technique. Calculate the total dose of AMONDYS 45 to be administered based on the patient's weight and the recommended dose of 30 milligrams per kilogram.

Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients who were treated with AMONDYS 45. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion, interrupting or discontinuing the AMONDYS 45 infusion ( 2.4 , 5.1 ) 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. ( 5.2 , 13.2 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients who were treated with AMONDYS 45. If a hypersensitivity reaction occurs, institute appropriate medical treatment, and consider slowing the infusion [see Dosage and Administration ( 2.4 )] , interrupting, or discontinuing the AMONDYS 45 infusion and monitor until the condition resolves. AMONDYS 45 is contraindicated in patients with known serious hypersensitivity to casimersen or to any of the inactive ingredients in AMONDYS 45 [see Contraindications ( 4 )] . 5.2 Kidney Toxicity Kidney toxicity was observed in animals who received casimersen [see Use in Specific Populations ( 8.4 ) and Nonclinical Toxicology ( 13.2 )] . Although kidney toxicity was not observed in the clinical studies with AMONDYS 45, kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Kidney function should be monitored in patients taking AMONDYS 45.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity reactions [see Warnings and Precautions ( 5.1 )] The most common adverse reactions (incidence >20% and at least 5% higher than placebo) were upper respiratory tract infection, cough, pyrexia, headache, arthralgia, and oropharyngeal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sarepta Therapeutics, Inc. at 1-888-SAREPTA (1-888-727-3782) 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 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 the AMONDYS 45 clinical development program, 76 patients received at least one intravenous dose of AMONDYS 45 (30 mg/kg). All patients were male and had genetically confirmed Duchenne muscular dystrophy. Age at study entry was 7 to 20 years (mean 9.9 years). Most (88%) patients were White, and 9% were Asian. AMONDYS 45 was studied in a double-blind, placebo-controlled study (Study 1). Patients in ongoing Study 1 received AMONDYS 45 (n=57) 30 mg/kg or placebo (n=31) intravenously once weekly for up to 96 weeks, after which all patients received or will receive AMONDYS 45 30 mg/kg for up to 48 weeks. Adverse reactions observed in ≥20% of patients treated with AMONDYS 45 and 5% more frequently than in the placebo group in Study 1 are shown in Table 1 . Table 1.

8.1 Pregnancy Risk Summary There are no human or animal data available to assess the use of AMONDYS 45 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 AMONDYS 45 on milk production, the presence of casimersen in milk, or the effects of AMONDYS 45 on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for AMONDYS 45 and any potential adverse effects on the breastfed infant from AMONDYS 45 or from the underlying maternal condition. 8.4 Pediatric Use AMONDYS 45 is indicated for the treatment of DMD in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping, including pediatric patients [see Clinical Studies ( 14 )]. Juvenile Animal Toxicity Data Intravenous administration of casimersen (0, 100, 300, and 900 mg/kg) to juvenile male rats once weekly for 10 weeks (postnatal days 14 to 77) resulted in renal tubular degeneration/necrosis at the highest dose tested. No effects were observed on the male reproductive system, neurobehavioral development, or immune function.

Metabolism

The pharmacokinetics of casimersen was evaluated in DMD patients following administration of intravenous (IV) doses ranging from 4 mg/kg/week to 30 mg/kg/week (i.e., recommended dosage). Following a single IV dose of casimersen, C max was reached at the end of infusion.

• Feb 25, 2021NDANDA213026Sarepta Theraps Inc

1. 1Product Dose Omission Issue25731%
2. 2No Adverse Event16620%
3. 3Poor Venous Access10212%
4. 4Device Issue769.1%
5. 5Intentional Dose Omission748.9%
6. 6Malaise384.6%
7. 7Pyrexia334.0%
8. 8Covid-19313.7%
9. 9Influenza192.3%
10. 10Pneumonia172.0%
11. 11Product Distribution Issue172.0%
12. 12Dehydration161.9%
13. 13Cough151.8%
14. 14Fall151.8%
15. 15Illness141.7%

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

• Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD)
  Completed · Phase 3 · Interventional · 228 enrolled · Sarepta Therapeutics, Inc.
  NCT02500381updated 2025-11-18
• A Long-term Observational Study Evaluating Eteplirsen, Golodirsen, or Casimersen in Routine Clinical Practice
  Enrolling by invitation · Observational · 300 enrolled · Sarepta Therapeutics, Inc.
  NCT06606340updated 2025-09-10
• An Extension Study to Evaluate Casimersen or Golodirsen in Patients With Duchenne Muscular Dystrophy
  Terminated · Phase 3 · Interventional · 171 enrolled · Sarepta Therapeutics, Inc.
  NCT03532542updated 2024-09-19
• A 48-Week, Open Label, Study to Evaluate the Efficacy and Safety of AMONDYS 45, EXONDYS 51, VYONDYS 53 in Subjects With DuchenneMuscular Dystrophy Carrying Eligible DMD Duplications.
  Completed · Phase 2 · Interventional · 3 enrolled · Kevin Flanigan
  NCT04179409updated 2023-10-26
• Dose-Titration and Open-label Extension Study of SRP-4045 in Advanced Stage Duchenne Muscular Dystrophy (DMD) Patients
  Completed · Phase 1 · Interventional · 12 enrolled · Sarepta Therapeutics, Inc.
  NCT02530905updated 2021-05-17

Frequently asked questions

How does Casimersen work?

Casimersen is designed to bind to exon 45 of dystrophin pre-mRNA resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 45 skipping. Exon 45 skipping is intended to allow for production of an internally truncated dystrophin protein in patients with genetic mutations that are amenable to exon 45 skipping [see Clinical Studies ( 14 )] .

What is Casimersen used for?

According to FDA labeling, Casimersen carries indications including: AMONDYS 45 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 45 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45 [see Clinical Studies ( 14 )] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Casimersen?

Casimersen is classified as Other drugs for disorders of the musculo-skeletal system, Antisense Oligonucleotide, Gene Alterations, Increased Protein Synthesis.

What are the brand names for Casimersen?

Casimersen is marketed under brand names including Amondys 45.

What are the contraindications for Casimersen?

Casimersen labeling lists contraindications including: AMONDYS 45 is contraindicated in patients with known serious hypersensitivity to casimersen or to any of the inactive ingredients in AMONDYS 45. Instances of hypersensitivity, including angioedema and anaphylaxis, have occurred in patients receiving AMONDYS 45 [see Warnings and Precautions ( 5.1 )] .. Always consult the full prescribing information and a clinician.