Amondys 45 (casimersen) for Duchenne muscular dystrophy
Fact-checked by Joana Carvalho, PhDWhat is Amondys 45 for muscular dystrophy?
Amondys 45 (casimersen) is an approved antisense oligonucleotide therapy for the treatment of Duchenne muscular dystrophy (DMD) in people with certain DMD gene mutations. The therapy’s approval by the U.S. Food and Drug Administration (FDA) is provisional, meaning that additional evidence of its clinical benefit in confirmatory clinical trials is required for its full continued approval.
DMD is caused by mutations in the DMD gene, which provides instructions for producing the dystrophin protein. Most DMD mutations result in little or no functional dystrophin being produced, leaving muscle cells vulnerable to damage and causing muscles to gradually weaken over time.
Genes are divided into sections called exons that fit together to produce proteins. Certain DMD-causing mutations lead to the loss of specific exons, preventing the remaining ones from fitting together correctly and disrupting dystrophin production.
Amondys 45 is a type of exon-skipping therapy that works by directing muscle cells to skip over exon 45 in the DMD gene, letting the remaining ones fit together better. This enables a shorter, but still functional version of the dystrophin protein, to be produced, which is expected to slow muscle strength decline. The therapy is specifically indicated for people with DMD who have mutations that are amenable to exon 45 skipping.
Developed by Sarepta Therapeutics, Amondys 45 is administered through an intravenous, or into-the-vein, infusion.
Therapy snapshot
| Brand name | Amondys 45 |
| Chemical name | Casimersen |
| Usage | Used to treat DMD in people with a confirmed DMD gene mutation that is amenable to exon 45 skipping |
| Administration | Intravenous infusion |
Who can take Amondys 45?
Amondys 45 is approved in the U.S. for people with DMD who have a mutation in the DMD gene that is amenable to exon 45 skipping. Genetic testing is needed to confirm whether a person’s DMD gene mutation is amenable to treatment with Amondys 45.
Its approval was granted through the FDA’s accelerated approval pathway, which allows swift approval for treatments of serious conditions based on biological markers indicating they are likely to provide clinical benefits. In the case of Amondys 45, accelerated approval was granted based on an increase in dystrophin production seen in the skeletal muscles of treated patients.
According to its prescribing information, the medication is contraindicated, meaning it should not be used, in people with with a history of serious hypersensitivity to Amondys 45’s active or inactive ingredients.
How is Amondys 45 administered?
Amondys 45 is administered once weekly by a trained healthcare provider through an intravenous infusion, which takes about 35 to 60 minutes to complete.
The recommended dosage is 30 milligrams per kilogram of body weight.
Amondys 45 in clinical trials
In the U.S., Amondys 45’s accelerated approval was supported by data from a Phase 3 clinical trial called ESSENCE (NCT02500381), which enrolled more than 200 boys, ages 6-13, with DMD who carried mutations that were amenable to exon 45 or exon 53 skipping.
Participants were randomly assigned to receive active treatment with Amondys 45 or Vyondys 53 (golodirsen) — another treatment for people with DMD with mutations that are amenable to exon 53 skipping — or a placebo for 96 weeks (nearly two years). This was followed by a 48-week open-label extension period where all patients received active treatment.
An interim analysis showed that mean dystrophin levels were significantly elevated in Amondys 45-treated patients, increasing from 0.93% of normal at the start of the study to 1.74% of normal after 48 weeks, or nearly a year, of treatment.
However, recently shared results showed that the trial failed to meet its main goal of demonstrating the ability of active treatment to significantly improve patients’ mobility after 96 weeks based on 4-step ascend velocity — a test that measures the speed at which a person can climb four stairs. Still, other mobility measures assessed as secondary endpoints favored active treatment. No new safety concerns were identified through 144 weeks.
Sarepta has submitted ESSENCE findings to request a traditional approval for Amondys 45 and Vyondys 53. The U.S. Food and Drug Administration accepted the application for review and set a target decision date for next year.
Amondys 45 side effects
The most common side effects associated with Amondys 45 include:
- upper respiratory tract infection
- cough
- fever
- headache
- joint pain
- pain in the mouth or throat
Amondys 45’s prescribing information also includes warnings about potentially serious risks, including:
- Severe allergic reactions, including anaphylaxis — a potentially life-threatening allergic reaction that can cause swelling of the throat or tongue, trouble breathing, or a drop in blood pressure. If these reactions occur, Amondys 45 infusions may need to be slowed, interrupted, or discontinued until the condition resolves.
- Kidney toxicity was observed in preclinical studies of Amondys 45. Although kidney toxicity was not observed in clinical trials, kidney function should be monitored in patients taking Amondys 45 through urine and blood tests.
Muscular Dystrophy News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
