General Information

Amondys 45 (casimersen) is an antisense oligonucleotide and uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 45 of dystrophin pre-mRNA, resulting in exclusion, or “skipping,” of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 45 skipping. 

Amondys 45 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 45 skipping.

Amondys 45 is supplied as a solution for intravenous injection. 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.

Clinical Trials

This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45. Continued approval may be contingent upon verification of a clinical benefit in confirmatory trials.

The FDA accelerated approval was based on an ongoing, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of Amondys 45 in ambulatory patients. The study is planned to enroll a total of 111 patients, age 7 to 13 years, randomized to Amondys 45 or placebo in a 2 to 1 ratio. Patients were required to have been on a stable dose of oral corticosteroids for at least 24 weeks prior to dosing with Amondys 45 or placebo. Following the 96-week double-blind period, all patients began or are to begin an additional 48 week open-label treatment period. Interim efficacy was assessed based on change from baseline in the dystrophin protein level (measured as % of the dystrophin level in healthy subjects, i.e., % of normal) at Week 48 of Study 1. In the study, patients who received Amondys 45 showed a significantly greater increase in dystrophin protein levels from baseline to week 48 of treatment compared to those who received placebo.

Side Effects

Adverse effects associated with the use of Amondys 45 may include, but are not limited to, the following: 

• upper respiratory tract infection
• cough
• pyrexia
• headache
• arthralgia
• oropharyngeal pain

Mechanism of Action

Amondys 45 (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.

Additional Information

For additional information regarding Amondys 45 or Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping, please visit the Amondys 45 website.