dm+d

Unassigned

New Medicines

Duchenne muscular dystrophy with 45‐exon skipping activity in patients aged 7 to 16 years

Information

New molecular entity
Sarepta Therapeutics
Sarepta Therapeutics

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Approved (Licensed)
Mar 21Approved in US [7]
Aug 20FDA accepts NDA for casimersin for Priority Review, with a regulatory action date of 25/2/2021, and grants conditional approval of brand name AMONDYS 45 [5].

Category

Weekly administered RNA‐based therapeutic and phosphorodiamidate morpholino oligomers (PMOs) which bind to RNA and efficiently interfere with gene expression in a sequence-specific manner.
DMD affects approximately 1 in every 3,500 boys that are born but only around 1 in 50 million girls [1]. In the UK, about 100 boys are born with DMD each year, and there are about 2,500 boys living with the condition at any one time [2].
Duchenne muscular dystrophy with 45‐exon skipping activity in patients aged 7 to 16 years
Intravenous infusion

Trial or other data

Mar 19Interim analysis of PIII ESSENCE trial shows that, in the casimersen arm, mean dystrophin protein (% normal dystrophin as measured by western blot) increased to 1.736% of normal vs. a mean baseline of 0.925% of normal (p<0.001). A statistically significant difference in the mean change from baseline to week 48 in dystrophin protein was observed between the casimersen-treated arm vs. placebo (p=0.009) [6].
Nov 18 anticipated primary completion now May 2022 [4].
Mar 18 PIII ESSENCE trial is still recruiting & expects to complete collection of primary outcome data in Sep 19 [3].
Aug 16PIII ESSENCE trial to evaluate the efficacy of casimersen and SRP 4053 vs. placebo in DMD patients with deletions amenable to skipping exon 45 and exon 53, respectively starts (4045-301; NCT02500381). Patients aged 7 to 13 years, will be randomised to receive once weekly IV infusions of 30 mg/kg casimersen or 30 mg/kg SRP-4053 respectively or placebo for up to 96 weeks, followed by an open label extension period, where all patients will receive open-label casimersen or SRP-4053 treatment for up to 96 weeks. The primary endpoint is defined as change in 6 minute walk test (6MWT) from baseline to week 96. 99 patients will be enrolled in the US, Belgium, Canada, France, Germany, Italy, Netherlands, Sweden and the UK [3].