Positive phase I/II results for brogidirsen in Duchenne muscular dystrophy

Brogidirsen is a dual-targeting phosphorodiamidate morpholino oligomer (PMO) antisense oligonucleotide composed of two sequences targeting exonPartie codante de l’ADN au sein d’un gène. 44 of the DMD gene in Duchenne muscular dystrophy. A Japanese 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 clinical trial involving six patients aged between 4 and 13 years demonstrated its ability to partially restore dystrophin expression.

• Of the six patients, five had a deletion of exon 45 and one had a 45-54 deletion.
• A significant induction of exon 44 skipping was found, with an increase of 32% between inclusion and the end of follow-up in all six patients.
• The level of dystrophin expression represented 24.47% of the expression level of healthy individuals with a dose of 80 mg/kg per week and 16.63% with a dose of 40 mg/kg per week.
• Motor function was stable in all patients, with a trend towards improvement.
• In vitro« Dans le verre », expériences réalisées en laboratoire en dehors de l’organisme. experiments using urine samples from patients also showed that brogidirsen allowed skipping of exon 44 and restoration of dystrophin levels.
• No serious adverse effects were reported.

These results justified an extension phase of this trial until 2026.

Phase 1/2 trial of brogidirsen: Dual-targeting antisense oligonucleotides for exon 44 skipping in Duchenne muscular dystrophy. Komaki H, Takeshita E, Kunitake K et al. Cell Rep Med. 2025 Jan.