Background: Suvodirsen is a stereopure antisense oligonucleotide recently under investigation as a therapy for Duchenne muscular dystrophy patients amenable to exon 51 skipping. The Phase 1 open-label extension (OLE) study was designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory functional effects of weekly suvodirsen for 96 weeks.
Objectives: To report the analysis of safety, tolerability, and dystrophin levels from baseline to 12 or 22 weeks in the Phase 1 OLE study of suvodirsen.
Approach: The interim analysis was from a global multicenter OLE study of suvodirsen in patients who previously enrolled in a Phase 1 study. A total of 36 patients enrolled in the OLE and received doses of either 3.5 mg/kg or 5 mg/kg. A baseline deltoid muscle biopsy was collected prior to OLE dosing. A second biopsy was collected after 12 or 22 weeks of treatment at 3.5 or 5 mg/kg. A quantitative western blot was used to assess changes in dystrophin amount. Safety assessments included adverse events, physical exams, vital signs, electrocardiogram, and clinical laboratory evaluations.
Results: At data cut-off, follow-up deltoid muscle biopsies were available for 27 of 36 patients. Within the 5 mg/kg arm, 10 patients received follow-up muscle biopsies at 12 weeks and nine patients received follow-up biopsies at 22 weeks. Within the 3.5 mg/kg arm, eight patients received follow-up muscle biopsies at 22 weeks. Muscle biopsies showed no change from baseline in dystrophin expression with either the 3.5 mg/kg or 5 mg/kg suvodirsen doses. No safety concerns or emerging safety signals were observed.
Conclusions: Based on Phase 1 OLE results showing no change from baseline in dystrophin expression, development of suvodirsen has been discontinued. Work is ongoing to fully analyze these results with the intention to share with the DMD community and hopefully advance the development of new DMD treatments.