Brogidirsen is a dual-targeting phosphorodiamidate morpholino oligomer (PMO) antisense oligonucleotide composed of two sequences targeting exon 44 of the DMD gene in Duchenne muscular dystrophy. A Japanese phase I/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 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.
