New Medicines

Duchenne muscular dystrophy


New molecular entity
Sarepta Therapeutics

Development and Regulatory status

Phase III Clinical Trials
Feb 22Roche now plans to file in EU & US in 2023 [14].
Jan 22Sarepta plans to complete enrolment in the middle of this year on its pivotal trial of SRP-9001 (EMBARK) and is expected to file in US in 2023. Results from the study and other existing trials could form the basis for a "feasible" early accelerated approval. The new data looks supportive albeit not definitive [12].
Nov 21According to latest pipeline, filings in the EU and US will now be until 2024 at the earliest [13].
Nov 21SRP-9001 has fast track, rare paediatric disease and orphan drug status in US. Also orphan drug status in EU [10].
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 using a recombinant adeno-associated virus serotype rh74 (rAAVrh74) capsid carrying micro-dystrophin, a shortened version of the human dystrophin gene, under the control of a human muscle-specific promotor (MHCK7). It replaces the missing protein in DMD-deficient skeletal and cardiac muscle and so restores muscle function. Given as a single dose.
DMD affects about 1 in 3,500 newborn males [1].
Duchenne muscular dystrophy
Intravenous infusion

Further information

Topic prioritised for potential TA guidance production

Trial or other data

Jul 22One-year functional data from ENDEAVOR study which employs commercially representative SRP-9001 at the target commercial dose. The data, from Cohort 1, showed a 3.8-point improvement and 3.2-point improvement (least squared means) on the North Star Ambulatory Assessment (NSAA) 52 weeks after treatment vs. control. Pts demonstrated statistically significant and clinically meaningful benefit vs. propensity-matched external controls, with results positively diverging from the natural history of the disease. Sarepta also presented long-term results from the SRP-9001-101 study after 4 years. Pts had a positive mean 7-point difference in total NSAA scores vs. baseline. Safety and tolerability were similar to past reports, with the most common adverse event being vomiting. Transient increases in liver enzymes and 1 serious event of myocarditis was also reported in the ENDEAVOR study. [17]
May 22A collaborative analysis by Pfizer, Sarepta, Genethon and Solid Biosciences, who are all working on gene therapies for DMD, analysed safety data and presented it at the American Society of Gene and Cell Therapy Meeting. Serious adverse events (SAE) were marked by muscle weakness and variable cardiac involvement, with similar clinical symptoms and time course. SAEs were observed in 5 pts across 3 trials, occurring ~3-7 weeks after infusion of gene therapies. The companies believe that because of similarities across multiple gene therapies using different capsids, promoters and transgene sequences, SAEs are most likely to be a specific transgene/genotype-related class effect. They suggest that the mechanism of the SAEs was a T-cell mediated immune response to the transgene protein expressed by all of the therapies in a cross-reactive immune response, determined by the pts genotypes since the SAEs only occurred in pts with specific genomic deletions; N-terminal epitopes, which are present in the transgene protein.[16]
Jan 22Positive topline results announced from part 2 of the SRP-9001-102 study (Study 102) of delandistrogene moxeparvovec in 41 pts with DMD. Pts from the placebo crossover group (from Part 1) scored 2 points higher on the NSAA (a 17-item score that measures functional motor abilities in ambulant pts with DMD) at week 48. The safety profile remained consistent with Part 1 outcomes, with no deaths, study discontinuations or treatment-linked serious adverse events. Study 102 is ongoing. [11]
Nov 21In the PIII EMBARK trial (NCT05096221), one group of participants will receive single IV infusion of SRP-9001 on Day 1, and a single IV infusion of matching placebo at Year 2. In the other group, the order will be reversed. Collection of primary outcome data is due to complete Oct 23. Recruitment is taking place only in the US [9].
Oct 21EMBARK PIII pivotal trial commenced (n=120, ages 4 to 7). The primary endpoint will assess the change in NSAA total score from baseline to week 52 compared to placebo. [8]
Oct 21Company presents results from Study 101 and 102. Study 101 (n=4, ages 4 to 7) found pts improved 8.6 points on the North Star Ambulatory Assessment (NSAA)* vs matched natural history cohort 3 years following a single administration of SRP-9001 (p<0.0001). In study 102 (n=12, ages 6 to 7), pts had a positive 2.9-point difference on NSAA change from baseline vs a matched natural history control one year after treatment (p=0.0129). Functional results from ENDEAVOR Cohort 1 (n=11, ages 4-7) found pts improved 3.0 points on NSAA 6 months after treatment. The safety and tolerability profile of SRP-9001 is similar to past reports. [8]
May 21Sarepta announce positive 12-week expression and safety results from the first 11 pts enrolled in the ENDEAVOR study. They showed robust transduction, delivering mean vector genome copies of 3.87 per nucleus and achieved mean micro-dystrophin expression levels of 55.4% of normal as measured by western blot. Pts achieved mean percentage of dystrophin positive fibers of 70.5% and intensity of micro-dystrophin expression of 116.9% of normal control, as measured by immunofluorescence (IF). No data on functional ability were reported. The safety profile consistent with prior studies and no new safety signals identified. Two pts experienced serious adverse events (transaminase elevation in one patient and nausea and vomiting in a second patient) that fully resolved. [7]
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].

Evidence based evaluations