Patient Dies of Acute Liver Failure After Treatment With Sarepta’s DMD Gene Therapy Elevidys

A patient has died of acute liver failure (ALF) after being treated with Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), a marketed adeno-associated virus (AAV) vector-based gene therapy intended to treat Duchenne muscular dystrophy (DMD).¹

Acute liver injury is known to be a possible adverse event associated with AAV vector-based gene therapies such as Elevidys, and is listed as such in the prescribing information for the gene therapy. It thus does not constitute a new safety signal. Although, the patient in question, identified as a young man, is the first to have died from ALF after treatment with Elevidys, out of over 800 patients who have received the product across clinical trials and the real-world setting. Sarepta stated that it still considers the benefit-risk of Elevidys to be positive.

Furthermore, Sarepta noted that the patient had recently experienced a cytomegalovirus (CMV) infection that the investigators noted may have contributed to the patient’s death. The company pointed out that information gathering and analysis related to the patient’s death is ongoing and that the event has been reported to appropriate health authorities, clinical trial investigators, and prescribing doctors. The prescribing information for Elevidys will be amended to include representation of this event.

New data from part 2 of the completed phase 3 EMBARK clinical trial (NCT05096221; SRP-9001-301) evaluating Elevidys in patients with DMD who are ambulatory were recently announced by the company in January 2025.² With regard to safety, the company stated that no new safety signals had been reported at that time.

“We’re very encouraged to see the results from part 2 of EMBARK as they further elucidate the impact Elevidys has on disease progression in a blinded, controlled study,” Louise Rodino-Klapac, PhD, the executive vice president, head of R&D, and chief scientific officer of Sarapeta, said in a January 2025 statement.² “Skeletal muscle MRI demonstrates the importance of preserving muscle, and the functional outcome results show disease stabilization sustained through 2 years after treatment. Over time, we continue to observe a statistically significant difference favoring Elevidys compared to a well-matched external control on NSAA and timed tests. The consistency and totality of evidence supporting a long-term and clinically meaningful treatment benefit with Elevidys continues to grow. We look forward to sharing more details with the clinical community in upcoming scientific forums.”

Sarepta is not the first company to report a patient death following treatment with a DMD gene therapy. In May 2024, Pfizer announced that a patient treated with fordadistrogene movaparvovec (PF-06939926), an investigational AAV vector-based gene therapy for DMD, had died after treatment in the context of the phase 2 DAYLIGHT study (NCT05429372), which was open to patients aged 2 to less than 4 years.³ In response to the death, Pfizer paused dosing associated with the crossover portion of the phase 3 CIFFREO clinical trial (NCT04281485), another study evaluating the gene therapy against standard of care in boys with DMD aged 4 to less than 8 years. The dosing pause did not apply to other studies evaluating fordadistrogenemovaparvovec as dosing had been completed in those studies.

In July 2024, Pfizer decided to discontinue development of fordadistrogene movaparvovec.⁴ The move came less than 2 months after the company announced that CIFFREO had failed to achieve its primary end point.⁵

“In light of the disappointing results, Pfizer does not have plans to continue development of fordadistrogene movaparvovec,” a Pfizer spokesperson said in a statement issued to CGTLive® at the time. “We will continue to closely monitor all participants that have received treatment in the clinical studies, and we are committed to sharing detailed results from the study at medical and patient advocacy forums to ensure that learnings from the trial can help improve future research and development of treatments for boys living with DMD.”

REFERENCES
1. Sarepta Therapeutics shares safety update on Elevidys. News release. Sarepta Therapeutics, Inc. March 18, 2025. Accessed March 18, 2025. https://investorrelations.sarepta.com/static-files/0d505d91-6722-4528-aae0-1e99fcbc37e5
2. 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 Therapeutics, Inc. January 27, 2025. Accessed March 18, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-results-part-2-embark-study?_ga=2.44245095.2103940291.1738162169-1590731373.1738162169
3. Letter. Pfizer. https://www.parentprojectmd.org/wp-content/uploads/2024/05/Pfizer-DMD-PAG-Letter_Final.pdf
4. Pfizer officially calls it quits on DMD gene therapy, lays off staff at Sanford site. News article. Elizabeth S. Eaton. FirstWordPharma. July 29, 2024. Accessed March 18, 2025. https://firstwordpharma.com/story/5880030
5. Pfizer provides update on phase 3 study of investigational gene therapy for ambulatory boys with Duchenne muscular dystrophy. News release. June 12, 2024. Accessed March 18, 2025. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-provides-update-phase-3-study-investigational-gene