Results from several clinical trials of SRP-9001 show the investigative gene therapy induces sustained functional improvements in people with Duchenne muscular dystrophy (DMD). While presenting these data, Sarepta (the manufacturer) also offered more details about the recently launched and pivotal Phase 3 EMBARK trial.
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).
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.
Doug Ingram, President and CEO of Sarepta, said in a company press release, “With 77 patients treated to date, the multi-study development program for SRP-9001 represents the most comprehensive and long-term dataset for a Duchenne muscular dystrophy gene therapy in existence,”
“We commence our EMBARK pivotal trial — currently the only truly global Phase 3 trial with a Duchenne gene therapy — with great conviction in the transformative potential of SRP-9001,” Ingram added.
SRP-9001 uses a ionnocuous virus to deliver the gene encoding micro-dystrophin directly to muscle cells for targeted production of a micro-dystrophin protein. In Duchenne, mutations in the DMD gene results in little or no dystrophin protein production, affecting muscles, but the gene’s large size necessitated a “micro” version.
The proof-of-concept Phase 1/2 study, called Study 101 (NCT03375164), is following four DMD boys, ages 4–7 at enrollment, for five years to assess the therapy’s safety and efficacy over time. All were treated with a single infusion dose of SRP-9001, and the trial is due to conclude in April 2023. These children are also being evaluated for changes with treatment in micro-dystrophin levels, in the North Star Ambulatory Assessment (NSAA) total scores (a 17-item test of motor abilities in Duchenne patients), as well as in the 100-meter timed test.
The new data shows that patients’ NSAA scores had improved by 8.6 points over the three years since being given SRP-9001, when compared with a matched natural history patient group. The natural history study follows a disease’s course in the absence of investigative treatment.
“When compared to a matched natural history cohort, individuals with Duchenne who received SRP-9001 are performing better on the NSAA or showing stabilization of NSAA scores where we would expect to see a decline,” said Louise Rodino-Klapac, PhD, an executive vice president and chief scientific officer at Sarepta.
In the double-blind and two-part Phase 2 trial, called Study 102 (NCT03769116), 41 boys with DMD, ages 4 to 7, were randomized to a single infusion of SRP-9001 or a placebo. Part one’s main goals were micro-dystrophin gene expression at 12 weeks, and changes from baseline (study start) in NSAA total scores at 48 weeks (about one year).
The open-label Phase 1 ENDEAVOR (NCT04626674), being conducted with Roche, enrolled 32 DMD patients: 20 boys, ages 4–7, and 12 older patients, both ambulatory (able to walk) and non-ambulatory. All are being given a single infusion of a commercially manufactured version of SRP-9001, and evaluated for five years for changes from baseline in micro-dystrophin protein levels, and treatment safety. Changes in motor skills are exploratory endpoints (goals).
The first 11 boys treated showed a significant 3.0-point improvement in NSAA scores at six months, compared with their baseline scores, new data showed.
“The functional results from Study 103 [ENDEAVOR] provide additional confidence in our ability to confirm a treatment effect with SRP-9001 as we advance our pivotal Phase 3 trial,” Rodino-Klapac said. SRP-9001’s safety and tolerability profile across these studies continues to be similar to past reports, Sarepta reported. Treatment-related adverse events observed generally occurred within 90 days of treatment and resolved; the most common was vomiting, usually within the first week post-infusion.
