With toxicity signal neutralised, Sarepta pushes forward

New data in three subjects treated with SRP-9003, Sarepta’s gene therapy for limb girdle muscular dystrophy, suggest that the highest dose will be taken into pivotal development next year. Expression results released today point to a dose response and, perhaps more importantly, no liver toxicity signal was seen. Two of three patients treated with a lower dose had elevated liver enzymes, but longer use of steroids helped avoid this problem in the next cohort, the company said. More functional data from cohort 1 were also released, and this too made for encouraging reading: all three patients improved on the nine-month cut of the results, disclosed last year. One outstanding question is what any pivotal trial of SRP-9003 might look like, and Sarepta executives are saying little for now. A placebo arm seems a likely requirement, echoing the design of the registrational study of SRP-9001, Sarepta’s lead Duchenne muscular dystrophy gene therapy. Bullish investors probably hope that the FDA will once again agree to a biomarker-based primary endpoint. Executives said more would be revealed on these plans early next year.  

Low and high dose cohorts in SRP-9003 phase I trial: expression results 
Metric Low dose High dose
  n=3, dosed at 5x1013vg/kg  n=3, dosed at 2x1014vg/kg
Mean percentage of beta-sarcoglycan +ve fibres 51% 72%
Mean beta-sarcoglycan expression by Western blot 36% of normal 62% of normal 
Mean creatinine kinase reduction 90% 89%
Serious adverse events  Liver enzyme elevation in 2 of 3 subjects Dehydration resulting from vomiting 3 days after infusion
Source: Sarepta presentations.
Sarepta presentation.

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