Background:
Golodirsen is a synthetic oligomer designed to restore the mRNA reading frame in patients (pts) with DMD gene mutations amenable to exon 53 skipping. We report the safety and efficacy of long-term golodirsen treatment in this first-in-human, phase 1/2, 2-part, multicenter trial.
Methods:
12 pts from part 1 (randomized, 12-week dose-titration phase; golodirsen [n = 8], placebo [n = 4]) plus 13 additional pts with genotypically confirmed DMD amenable to exon 53 skipping therapy were included in part 2 (open label). All 25 pts received continuous open-label treatment with once-weekly golodirsen 30 mg/kg. Safety and measures of pulmonary and functional efficacy were assessed.
Results:
Golodirsen-treated pts had a median age of 8 years. Safety data were collected up to 189 weeks, and median golodirsen exposure was 168 wks. All golodirsen-treated pts experienced ≥1 treatment-emergent AE (TEAE), including rhinitis, nasopharyngitis, headache, and proteinuria. Overall, 12 pts (48%) had mild TEAEs, 8 (32%) experienced moderately severe TEAEs and 5 (20%) had severe TEAEs. All severe TEAEs were nonserious and considered unrelated to golodirsen. There were no deaths or discontinuations due to golodirsen.
Ambulatory assessments were reported, including 6MWT and NSAA scores relative to baseline. Further, respiratory function was evaluated by percent FVC change from baseline.
Conclusions:
Long-term treatment with golodirsen was well tolerated. No patient discontinued because of an AE. These data, and the previously reported encouraging data on dystrophin protein expression at 48 weeks, support further clinical development of golodirsen for the treatment of DMD. Comparisons to well-matched natural history cohorts are underway.