EMA Issues Negative Opinion for Sarepta’s Gene Therapy Elevidys

Levi Garraway, MD, PhD

In a regulatory update, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a negative opinion on the conditional marketing authorization (CMA) for Elevidys (Sarepta/Roche), a gene therapy for Duchenne muscular dystrophy (DMD). The companies are expected to work with the agency to explore a potential path forward.¹

The CHMP’s opinion was specifically for the therapy’s ability to treat ambulatory individuals with DMD aged 3 to 7. Results from Elevidy’s clinical program, along with data from the pivotal phase 3 EMBARK study (NCT05096221), a confirmatory trial, led to the agency’s decision. The news comes nearly a week after the FDA requested Sarepta and Roche to shut down the distribution of Elevidys following a third reported death in its gene therapy programs.

"We are disappointed by the CHMP’s negative opinion, given the urgent need for disease-modifying therapies for children in the EU living with Duchenne,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said in a statement.¹ "With an average life expectancy of only 28 years, achieving disease stabilisation is a major advance for individuals living with Duchenne, their families and caregivers. We are confident in the value Elevidys can bring to ambulatory patients."

EMBARK was a phase 3, randomized, placebo-controlled, 2-part study of 125 participants with DMD. In Part 1, patients were randomized by age (≥4 to <8 years) or North Star Ambulatory Assessment (NSAA) Total Score (>16 to <29) and received either Elevidys at 1.33 x 1014 vg/kg or placebo, with a 52-week follow-up. In Part 2, participants crossed over, switching treatments while remaining blinded for another 52-week follow-up.

Part 1 of the study, announced in late-2023, revealed that Elevidys did not meet its primary end point of change in NSAA total score at 52 weeks. Between Elevidys-treated patients and those on placebo, investigators reported a non-significant difference of 0.65 points (P = .24); however, the treatment did demonstrate robust results on key pre-specified end points over the treatment period. These included Time to Rise (least square mean [LSM] difference, –0.78; P = .0291), and 10-meter walk test (LSM difference, –0.42; P = .0048).²

Data from Part 2, first announced in January of this year, revealed that treatment with Elevidys led to statistically significant improvements in functional outcomes among those who switched from placebo, as well as continued benefits in preserving muscle function and disease stabilization over a 2-year period. At 52 weeks, patients treated with Elevidys showed a 2.34-point improvement in NSAA scores relative to a matched external control (P <.0001).³

Additional data from Part 2 clinically meaningful and statistically significant function benefits in NSAA, TTR (–2.70 seconds; P <.0001), and 10-meter walk/run function test (–1.07 seconds; P = .0001) in the crossover group despite being 1 year older than those treated in Part 1. After 2 years of treatment, those who originally received gene therapy in Part 1 demonstrated clinically meaningful and statistically significant functional benefit in NSAA (+2.88 points; P = .0001), TTR (–2.06 seconds [improvement]; P = .0033), and 10MWR (–1.36 seconds [improvement]; P = .0028) in comparison with the external control.

Elevidys, an adeno-associated vector-based gene therapy, was originally FDA-approved under the accelerated approval pathway in June 2023. Nearly a year later, the therapy received traditional approval for ambulatory DMD patients and an expanded label for those aged 4 and older. At the same time, it gained accelerated approval for nonambulatory patients, pending confirmation of clinical benefit in a follow-up trial.^4,5

The recent news surrounding patient deaths in Sarepta’s clinical trial program recently led to the FDA revoking the company’s platform technology designation, as well as requesting a voluntary half on all Elevidys shipments. Of the reported deaths, all 3 were related to liver failure. About a month before the 3^rd incident occurred, Roche announced dosing restrictions on the gene therapy, limiting its use in non-ambulatory patients with DMD, irrespective of age, in both clinical and commercial settings. At the time, the company announced it would halt gene therapy use in nonambulatory patients commercially and pause their enrollment and dosing in trials pending updated risk mitigation measures.⁶

REFERENCES
1. Roche provides regulatory update on Elevidys™ gene therapy for Duchenne muscular dystrophy in the EU. News release. July 25, 2025. Accessed July 25, 2025. https://www.globenewswire.com/news-release/2025/07/25/3121721/0/en/Roche-provides-regulatory-update-on-Elevidys-gene-therapy-for-Duchenne-muscular-dystrophy-in-the-EU.html
2. Sarepta Therapeutics announces topline results from EMBARK, a global pivotal study of ELEVIDYS gene therapy for Duchenne muscular dystrophy. News release. Sarepta Therapeutics. October 30, 2023. Accessed July 25, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-topline-results-embark-global-0
3. Sarepta Therapeutics Announces Results from Part 2 of the EMBARK Study Demonstrating Sustained Benefits and Disease Stabilization in Ambulatory Individuals with Duchenne Muscular Dystrophy Following Treatment with ELEVIDYS. News release. Sarepta. January 27, 2025. Accessed July 25, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-results-part-2-embark-study
4. Sarepta Therapeutics announces FDA approval of Elevidys, the first gene therapy to treat Duchenne muscular dystrophy. News release. June 22, 2023. Accessed July 25, 2025. https://www.businesswire.com/news/home/20230622454844/en/
5. Sarepta Therapeutics Announces Expanded US FDA Approval of ELEVIDYS to Duchenne Muscular Dystrophy Patients Ages 4 and Above. News Release. Sarepta Therapeutics. Published June 20, 2024. Accessed July 25, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-expanded-us-fda-approval-elevidys?_ga=2.261745871.332981042.1718920455-330115727.1718920455
6. [Ad hoc announcement pursuant to Art. 53 LR] Roche provides safety update on Elevidys™ gene therapy for Duchenne muscular dystrophy in non-ambulatory patients. Roche. June 15, 2025. Accessed July 25, 2025. https://www.globenewswire.com/news-release/2025/06/15/3099406/0/en/Ad-hoc-announcement-pursuant-to-Art-53-LR-Roche-provides-safety-update-on-Elevidys-gene-therapy-for-Duchenne-muscular-dystrophy-in-non-ambulatory-patients.html