Casimersen (SRP-4045, Amondys45), an antisense oligonucleotide targeting exon 45 skipping of the DMD gene, is one of the exon skipping agents developed in Duchenne muscular dystrophy (DMD) by Sarepta Therapeutics. It obtained conditional marketing authorisation (MA) in the United States in February 2021.
A phase I/II US trial studied this agent in limited ambulatory or non-ambulatory boys with DMD, for a period of more than two and a half years: the results were published in the journal Muscle & Nerve in June 2021.
Good tolerability and satisfactory elimination of SRP-4045 by the body
This trial was conducted in 12 participants aged 7 to 21 years, with DMD, experiencing difficulty walking or no longer able to walk:
- part 1 under double-blind conditions: 8 participants received treatment with increasing doses of casimersen (4, 10, 20 then 30 mg/kg/week) for 12 weeks (two weeks in succession per dose) and another 4 participants received placebo, by intravenous infusion.
- part 2 under open-label conditions: 12 participants received treatment with 30 mg/kg/week casimersen, for 132 weeks.
The adverse events reported over the duration of the trial concerned both the treatment group and the placebo group. These events were described as mild, and mainly involved pain at the injection site, headache, vomiting, nausea, back pain or pain in extremities, joint pain and papilloma.
Casimersen appears to undergo normal elimination from the body since the quantity of product in the blood does not increase over time (this is the same after 7 weeks of treatment as after 60 weeks). The medicinal product was effectively eliminated in the urine and does not appear to have any toxic effect on the kidneys.
These results are encouraging for further evaluation of casimersen in patients with progressive disease (limited or non-ambulatory).