Casimersen examined in a phase I/II trial in limited ambulatory or non-ambulatory DMD patients is well tolerated and eliminated over time

Casimersen (SRP-4045, Amondys45), an antisense oligonucleotide targeting exonPartie codante de l’ADN au sein d’un gène. 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 IAu cours d’un essai clinique de phase I un médicament dont l’intérêt thérapeutique a été montré sur des modèles animaux et/ou cellulaires (essais précliniques) est administré pour la première fois à un petit groupe de volontaires sains, plus rarement à des malades, afin d’évaluer leur tolérance à la substance en fonction de la dose (Comment le futur traitement est-il absorbé et éliminé ? Comment se fait sa répartition dans les organes ? Est-il toxique et à quelles doses ? Existe-t-il des effets secondaires ?)./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 placeboLe placebo est un produit dont la présentation est identique à celle d’un médicament, mais qui ne contient pas de principe actif. Dans un essai clinique, un placebo est utilisé pour mesurer l’action réelle du médicament testé, en comparant les effets du médicament testé contenant le principe actif et ceux du 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).

Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping : A randomized, double-blind, placebo-controlled, dose-titration trial. Wagner KR, Kuntz NL, Koenig E, East L, Upadhyay S, Han B, Shieh PB. Muscle Nerve. 2021 Jun 8.