SRP-9001 Safe, Tolerable in Duchenne Muscular Dystrophy


Preliminary results showed that SRP-9001 is associated with clinically meaningful improvement that is greater than that observed with standard-of-care treatment, including corticosteroids.

Jerry Mendell, MD

Jerry Mendell, MD

Results from Study 101, a phase 1/2a nonrandomized controlled trial (NCT03375164) revealed that treatment with SRP-9001 (rAAVrh.MHCK7.micro-dystrophin; Sarepta Therapeutics) was well-tolerated and had minimal adverse events (AEs) in ambulatory men with Duchenne muscular dystrophy (DMD) without preexisting AAVrh74 antibodies and a stable corticosteroid dose.1,2

Lead author Jerry Mendell, MD, neurologist, Nationwide Children’s Hospital, and colleagues found that among the 4 patients included in the study, all 53 AEs recorded were either considered mild (n = 33; 62%) or moderate (n = 20; 38%), while also reporting no serious AEs as well. Conducted at the Nationwide Children’s Hospital in Columbus, Ohio, researchers found 18 AEs were considered treatment-related, the most common of which was vomiting (9 of 18 events; 50%). Additionally, 3 patients had transiently elevated y-glutamyltransferase, which resolved with corticosteroids.

With safety as the primary outcome, secondary outcomes included micro-dystrophin expression by Western blot and immunohistochemistry. After 12 weeks, immunohistochemistry of gastrocnemius muscle biopsy specimens revealed robust transgene expression in all patients, with a mean of 81.2% of muscle fiber micro-dystrophin with a mean intensity of 96% at the sarcolemma.

Western blot showed a mean expression of 74.3% without fat or fibrosis adjustment and 95.8% with adjustment. Notably, all patients had confirmed vector transduction and showed functional improvement of North Star Ambulatory Assessment (NSAA) at posttreatment compared with baseline that was maintained for 1 year.

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In addition to the gene showing a safe profile and improvements on NSAA, patients maintained a reduction in creatine kinase levels for 1 year. Mendell and colleagues concluded that treatment with SRP-9001 can provide functional improvement that is greater than that observed under standard of care.

“We are very pleased to report successful delivery of the transgene to the nuclei corresponding to robust expression and proper localization of micro-dystrophin. This coincides with improvements in functional measurements in study participants who received SRP-9001,” Wendell said in a statement.

Study 101 was an open-label trial that infused SRP-9001 at a dose of 2x1014 vg/kg via peripheral arm vein in all 4 of the ambulatory patients with DMD between the ages of 4 and 7 without preexisting AAVrh74 antibodies and a stable corticosteroid dose of ≥12 weeks. In addition to receiving SRP-9001, patients were given daily prednisolone, 1 mg/kg, at day 1 prior to gene delivery. With that, they also underwent a 30-day taper after infusion.

SRP-9001 is an investigational gene therapy intended to deliver the micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. Researchers noted that micro-dystrophin gene transfer has shown promise for treating patients with DMD by using adeno-associated virus serotype rh74 (rAAVrh74) and codon-optimized human micro-dystrophin driven by a skeletal and cardiac muscle-specific promotor enhanced cardiac expression (MHCK7).

As previously mentioned, safety, based on number of participants with adverse events, was the primary outcome measure of the study. Other secondary outcome measures included Gross Motor Subtest Scaled (Bayley-III) score, NSAA, and The 100 Meter Timed Test.

“Following the 9-month update we shared last year, the peer-reviewed publication of these results in JAMA Neurology further supports the potential for SRP-9001 to provide clinically meaningful functional improvements in terms of speed and magnitude of improvement for patients with DMD,” Louise Rodino-Klapac, PhD, senior vice president, Sarepta Therapeutics, said in a statement. “Study 102, our randomized, double-blind, placebo-controlled study of SRP-9001, is ongoing and we look forward to sharing the results in early 2021 as we work toward our ultimate goal of profoundly improving the lives of as many patients living with DMD as possible.”


1. Sarepta Therapeutics announces positive safety and efficacy data from the SRP-9001 micro-dystrophin gene therapy trial published in JAMA neurology. News release. Sarepta Therapeutics. June 15, 2020. Accessed June 19, 2020.

2. Mendell JR, Sahenk Z, Lehman K. Assessment of systemic delivery of rAAVrh74.MHCK7.micro-dystrophin in children with Duchenne muscular dystrophy: a nonrandomized controlled trial. JAMA Neurol. Published online June 15, 2020. doi: 10.1001/jamaneurol.2020.1484.

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