Sarepta Therapeutics’ SRP 9001 shows sustained functional improvements in multiple studies of patients with Duchenne.

SRP-9001, being developed in partnership with Roche, is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. In new analyses presented at “SRP-9001 Micro-dystrophin Day,” results from participants treated with SRP 9001 in Study SRP 9001 101 (n=4, ages 4 to 7) found that participants in Study 101 improved 8.6 points on the North Star Ambulatory Assessment (NSAA) compared to a matched natural history cohort three years following a single administration of SRP 9001 (p<0.0001).> In Study SRP 9001-102, SRP 9001-treated participants ages 6 to 7 (n=12) had a positive 2.9-point difference on NSAA change from baseline compared to a matched natural history control (p=0.0129).</0.0001).>

In addition, the first functional results were presented from Study SRP-9001-103 (ENDEAVOR) , which uses commercially representative SRP 9001 material. Results from the first 11 participants in Cohort 1, ages 4 to 7, demonstrated a 3.0-point improvement from baseline on NSAA six months after treatment.

The safety and tolerability profile of SRP 9001 is similar to past reports. Across all three studies, treatment-related adverse events (TRAEs) generally occurred within 90 days of treatment and subsequently resolved. No clinically relevant complement activation was observed? in any of the studies. The most common treatment-related adverse event was vomiting, generally within the first week post-infusion. Increases in liver enzymes were transient and responsive to steroids?. In Study 9001 103, safety data were consistent with data from previous studies of SRP 9001 (101 and 102). There was one immune-mediated myositis serious adverse event in Cohort 2? specific to the participant’s mutation; participant received treatment including plasmapheresis and has since returned to pre-event function.

About the SRP-9001 Clinical Development Program; The SRP-9001 clinical development program currently consists of four studies: EMBARK, Study SRP-9001-301: a global, randomized, double-blind, placebo-controlled clinical trial of commercially representative SRP-9001 material in 120 participants with Duchenne muscular dystrophy between the ages of 4 to 7. The primary endpoint will assess the change in NSAA total score from baseline to week 52 compared to placebo. Key features of EMBARK include stratification of participants by age and baseline NSAA, with a minimum of 50 percent of patients ages 4 to 5 enrolled. Inclusion criteria include a stable daily dose of oral corticosteroids for at least 12 weeks before screening and rAAVrh74 antibody titers of less than 1:400. Participants with mutations between or including exons 1-17 or mutations fully contained within exon 45 (inclusive) are not eligible. Secondary endpoints include the number of skills gained or improved at week 52 as measured by NSAA, the quantity of micro-dystrophin protein expression at week 12 (Part 1) as measured by western blot, timed function tests and safety. In Part 1, results from the treatment and placebo groups are compared through 52 weeks following treatment. In Part 2, the study remains blinded to investigators and participants while all participants in the placebo group cross over to active treatment and all participants are followed for another 52 weeks while safety and efficacy continue to be evaluated. ENDEAVOR, Study SRP-9001-103 (Study 103): an open-label clinical trial of SRP 9001 that has enrolled 32 participants with Duchenne muscular dystrophy, with 20 participants ages 4 to 7 and expanded cohorts that include older ambulant and non-ambulant individuals. Study 103 uses commercially representative SRP 9001 material and the primary endpoint is the change from baseline in the quantity of micro-dystrophin protein expression measured by western blot at 12 weeks. Secondary outcome measures include change from baseline in micro-dystrophin expression fiber intensity as measured by immuno-fluorescence and micro-dystrophin expression measured by IF percent dystrophin positive fibers at 12 weeks. Exploratory endpoints include the change in vector genome copies per nucleus, NSAA and certain timed functional tests. Including the initial 12-week period, patients will be followed for a total of five years.Study SRP-9001-102 (Study 102): a double-blind, 1:1 randomized, placebo-controlled clinical trial of SRP 9001 in 41 participants with Duchenne muscular dystrophy between the ages of 4 to 7. Study 102 uses clinical process SRP 9001 material and has two primary endpoints: micro-dystrophin expression at 12 weeks and change in NSAA total score at 48 weeks compared to placebo. Secondary endpoints include certain timed functional tests; micro-dystrophin expression measured by immuno-fluorescence fiber intensity; and micro-dystrophin expression measured by immuno-fluorescence percent dystrophin positive fibers. In Part 1, results from the treatment and placebo groups are compared through 48 weeks following treatment. In Part 2, the study remains blinded while all participants in the placebo group cross over to active treatment and all participants are followed for another 48 weeks while safety and efficacy continue to be evaluated and for five years total after infusion.SRP-9001-101 (Study 101): a single-center, open-label clinical trial of SRP 9001 to evaluate the safety, tolerability and proof of concept of a single dose of clinical process SRP 9001 material. The trial enrolled 4 ambulatory participants with Duchenne muscular dystrophy between the ages of 4 to 7. The primary endpoint was safety, and secondary endpoint included the change in micro-dystrophin expression pre- and post-treatment, decreases in creatine kinase, NSAA total score and timed function test. Participants are being followed for five years after treatment, while safety and efficacy continue to be evaluated. The NSAA is a 17-item rating scale that is used to measure functional motor abilities in ambulant children with Duchenne. It is used to monitor the progression of the disease and treatment effects which makes it suitable as an endpoint in clinical trials for Duchenne.