Sarepta's DMD Gene Therapy Elevidys Linked to Patient Death, Raising Safety Concerns

In a significant development for the gene therapy landscape, Sarepta Therapeutics has reported a patient death following treatment with its Duchenne muscular dystrophy (DMD) gene therapy, Elevidys. The incident has sparked renewed discussions about the safety profile of adeno-associated virus (AAV) vector-based gene therapies and their risk-benefit balance in treating rare genetic disorders.

Patient Death and Immediate Fallout

Sarepta announced that a 16-year-old male patient with DMD died due to acute liver failure after receiving Elevidys treatment. The company stated that while a recent cytomegalovirus (CMV) infection was identified as a possible contributing factor, they "cannot rule out the possibility that Elevidys was a contributing factor" to the death.

This marks the first reported fatality among over 800 patients who have received Elevidys in clinical trials or commercial settings. The news sent Sarepta's stock plummeting, with shares falling approximately 22% following the announcement.

Safety Concerns and Regulatory Implications

Acute liver injury is a known risk associated with AAV-based gene therapies, including Elevidys. The therapy's label already includes warnings about potential liver enzyme elevations, and patients are given steroids before and after treatment to mitigate this risk.

In response to the incident, Sarepta plans to update Elevidys' prescribing information to reflect this serious adverse event. The company has reported the case to health authorities and study investigators, emphasizing that patient safety remains their top priority.

This event draws parallels to previous safety concerns with other gene therapies. In 2022, Novartis reported two deaths from acute liver failure in patients treated with Zolgensma, its gene therapy for spinal muscular atrophy.

Efficacy and Approval Controversies

The patient death reignites debates surrounding Elevidys' efficacy and its controversial FDA approvals. Critics have questioned the therapy's effectiveness, as it missed primary endpoints in two clinical trials. Despite these concerns, the FDA granted Elevidys accelerated approval and later expanded its label to cover most DMD patients in the U.S., decisions that were made by overruling internal objections from agency reviewers.

Sarepta maintains that Elevidys' benefit-risk profile remains positive, citing data from the Embark trial showing improvements in motor function compared to external controls. However, the therapy's high price tag of $3.2 million per treatment has drawn criticism from some patient families, who argue for stronger efficacy evidence to justify the cost.

As the pharmaceutical industry grapples with this latest setback, the incident underscores the ongoing challenges in developing safe and effective gene therapies for rare genetic disorders. The coming months will likely see increased scrutiny of AAV-based therapies and potentially stricter safety monitoring protocols in clinical trials and commercial use.