New Medicines

Duchenne muscular dystrophy in ambulatory patients ages 4-7 years


New molecular entity
Sarepta Therapeutics

Development and Regulatory status

Phase II Clinical Trials
Feb 21SRP-9001 is considered by analysts to be the seventh anticipated drug launch of 2021 in the US, despite PII results. Sarepta pointed to an imbalance in the fitness of patients at baseline to explain the failure. In the small, 42-subject study, Sarepta grouped patients into two cohorts by age. Among 6- to 7-year-olds baseline NSAA scores were not that different, but in children aged 4 and 5, SRP-9001 was linked to a mean NSAA change of 4.3, significantly larger than the placebo arm with 1.9. Sarepta hopes learnings from the PII study will guide it to a better PIII design [6].
Jan 21SRP-9001 path to market may be delayed following failure to meet primary endpoint in PII trial. Sarepta is focused on generating full data from the ongoing study and a separate clinical trial [5].
Dec 19Sarepta announces a licensing agreement granting Roche the exclusive right to launch and commercialise SRP-9001 outside the United States. Sarepta is responsible for global development and manufacturing for SRP-9001 and plans to commercialize SRP-9001 in the US [3].


An in vivo gene therapy intended to deliver the micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. Given as a single infusion.
DMD affects about 1 in 3,500 newborn males [1].
Duchenne muscular dystrophy in ambulatory patients ages 4-7 years
Intravenous infusion

Trial or other data

Jan 21SRP-9001 has failed to meet endpoint of functional motor ability score improvement in PII trial. Sarepta believe results have been due to an imbalance between the two arms of the clinical trial [5].
Nov 20Study 101 is no longer recruiting and due to complete collection of primary outcome data in Apr 23; collection of primary outcome data in placebo-controlled Study 102 should complete next month [4].
Sep 20PII study (NCT03375164) is also known as Study 101 [2].
Sep 20PII study (NCT03769116) is also known as Study 102 [2].
Jun 20Sarepta announces safety and tolerability data at one year from four DMD clinical trial participants who received SRP-9001 micro-dystrophin (AAVrh74.MHCK7.micro-dystrophin) have been published in JAMA Neurology. In the open-label trial, known as Study 101, four ambulatory participants between the ages of 4 and 7 were treated with an infusion of SRP-9001 at a dose of 2x1014 vg/kg. The therapy was safe and tolerable in all participants over the one-year time period. All adverse events were considered mild or moderate, and there were no serious adverse events or evidence of complement activation. At 12 weeks, muscle dystrophin levels demonstrated a mean of 81.2% muscle fibers expressing micro-dystrophin with a mean intensity at the sarcolemma by immunohistochemistry of 96% compared to normal biopsies. Adjusted for fat and fibrotic tissue, western blot showed a mean expression of 95.8%. All participants had confirmed vector transduction and showed functional improvement on the North Star Ambulatory Assessment scale (NSAA) and reduced creatine kinase (CK) levels that were maintained through one year [3].
Mar 20PII study (NCT03769116) is no longer recruiting [2].
Dec 18PII study to evaluate the safety and efficacy of exogenous gene transfer in DMD patients by measuring biological and clinical endpoints in two parts: a 48-week randomized, double-blinded, placebo-controlled period (Part 1), and a 96-week, double-blinded extension period (Part 2) starts (NCT03769116). 41 boys aged 4 to 7 years will be recruited in the US. Primary outcomes are 1. Incidence of Serious Adverse Events (SAEs) up to Week 144; 2. Incidence of Treatment Emergent Adverse Events (TEAEs); 3. Change From Baseline in Quantity of Microdystrophin Protein Expression Measured by Western Blot from baseline up to Week 12. Collection of these data is due to complete Oct 22 [2].