Duchenne muscular dystrophy in patients who have genetic mutations subject to skipping exon 53 of the DMD gene
Development and Regulatory status
Dec 18: Sarepta completes submission of its New Drug Application (NDA) to the FDA seeking approval of golodirsen (SRP-4053) in patients with Duchenne muscular dystrophy amenable to skipping exon 53 .
Mar 18: Sarepta said it intends to file for approval of golodirsen to treat in pts who have genetic mutations subject to skipping exon 53 of the DMD gene. They hope to receive accelerated approvalprior to completion of the PIII ESSENCE trial. They anticipates filing for approval of golodirsen by the end of the year.·
Trial or other data
Feb 18: ESSENCE trial on temporary hold following one serious adverse event (SAE) that could possibly be related to the investigational drug product. The study remains blinded and the adverse event observed is consistent with those seen in pts with DMD. The safety data were reviewed by an independent Data Monitoring Committee (DMC). The DMC deemed that dosing could continue for all patients. However, the MHRA required that dosing stop at all UK sites. Sarepta is currently submitting an amendment to the MHRA. Following approval from the MHRA, dosing can be reinitiated at the UK sites.
Sep 17: Positive results from the phase I/II (4053-101; EudraCT2014-002008-25; NCT02310906) trial reported. Mean dystrophin protein increased to 1.019% of normal compared to a mean baseline of 0.095% of normal (p < 0.001) as measured by Western blot, the primary biological endpoint in the study - a 10.7 fold increase from baseline. Further, the study showed a statistically significant increase in dystrophin immunofluorescence as measured by immunohistochemistry (IHC), confirming sarcolemma-associated protein expression and distribution. The two-parts trial randomised 12 patients in part 1 and 13 patients in part 2 to receive a dose titration of golodirsen or placebo.
Aug 16: PIII, randomised, double-blind, parallel-assignment ESSENCE trial (4045-301; NCT02500381) initiated. This will evaluate the efficacy and safety of golodiresen vs. placebo, in pts aged 7-13 yrs with Duchenne muscular dystrophy (DMD) with deletions amenable to skipping exon 45 and exon 53, respectively. Pts will be randomised to receive once weekly IV infusions of 30 mg/kg SRP-4045 or 30 mg/kg golodiresen respectively or placebo for up to 96 weeks, followed by an open label extension period, where all patients will receive open-label SRP-4045 or golodirsen for up to 96 weeks. The primary endpoint was defined as change in 6 minute walk test (6MWT) from baseline to week 96. The trial intends to enrol 99 pts in the US, Belgium, Canada, France, Germany, Italy, Netherlands, Sweden and the UK.
Dec 14: Initiation of a randomised, double-blind, placebo-controlled dose escalation PI/II trial to evaluate the pharmacokinetics, safety and tolerability of golodiresen in ~48 pts aged 6-15 with DMD, responsive to exon 53 skipping (4053-101; EudraCT2014-002008-25; NCT02310906). Enrolment underway in France, the UK and Italy.·