Sarepta Takes Action to Strengthen ELEVIDYS Safety Measures in Non-Ambulatory Duchenne Patients
Sarepta Therapeutic a leading innovator in precision genetic medicine for rare disorders, today provided a significant safety update for ELEVIDYS (delandistrogene moxeparvovec-rokl). ELEVIDYS is currently the only U.S. Food and Drug Administration (FDA)-approved gene therapy for the treatment of Duchenne muscular dystrophy (DMD). The company’s updated guidance focuses on strengthening its safety profile in non-ambulatory patients following a second report of acute liver failure (ALF) that resulted in a patient’s death. Importantly, both cases of ALF have been reported exclusively in non-ambulatory individuals with Duchenne muscular dystrophy — a population that typically bears a heavy disease burden — underscoring the need for careful and tailored approaches to their care.
Sarepta expresses its profound condolences to the affected families and care teams, honoring their immense struggles and emphasizing its ongoing, relentless commitment to improving the lives of all individuals battling this rare, degenerative muscle disease.
Key Safety Initiatives Currently Underway
Sarepta is currently employing a range of measures designed to reduce the risk of acute liver failure in non-ambulatory Duchenne muscular dystrophy patients who may be candidates for ELEVIDYS. These initiatives reflect a careful and comprehensive approach to patient safety — and a strong understanding of the delicate balance between delivering a potentially life-changing therapy and mitigating its associated risks.
Evaluating and Enhancing the Immunosuppressive Regimen
As a crucial first step, Sarepta is proactively reviewing its current safety data alongside a team of leading experts in both Duchenne muscular dystrophy and liver health. This independent expert panel will aid in evaluating a new, enhanced immunosuppressive regimen meant to help ease the body’s adaptive immune response — a process suspected to contribute to the elevated liver enzyme abnormalities and related events that have been observed in a small number of patients following treatment with AAV-based gene therapy.
Sarepta’s team is exploring adding sirolimus — a well-established immunosuppressive medication — to the regimen in a way that might enable a greater degree of control over the patient’s immune response. This approach is supported by extensive preclinical data demonstrating its ability to reduce or ease potential complications stemming from excess liver enzyme elevations. Importantly, the independent expert panel’s recommendations will be reviewed by the FDA before implementation. The ultimate aim is to enable the administration of ELEVIDYS safely while honoring its potential to provide a dramatic and durable therapeutic benefit for children battling this profoundly challenging disease.
Temporary Suspensions of Shipments for Non-Ambulatory Patients
While the team assesses the enhanced regimen alongside regulators and expert advisors, Sarepta is temporarily suspending all new shipments of ELEVIDYS for non-ambulatory patients. This cautious and responsible step will enable the company to gather additional data, make appropriate and fully-informed decisions, and collaborate closely with regulators to enable eventual resumption under a more robust safety framework.
For ambulatory patients — those retaining some ability to walk — there are no new treatment interruptions or regimen modifications at this time. Standard prophylactic measures, including administration of corticosteroids before and after infusion and careful post-infusion follow-up, remain in place for these individuals.
ENVISION Study Dosing Currently Paused
Sarepta is also voluntarily pausing dosing in its ongoing ENVISION clinical study (Study SRP-9001-303), a trial that includes both non-ambulatory and ambulatory individuals with Duchenne muscular dystrophy. The FDA agrees with this cautious approach. This pause will enable Sarepta to incorporate the enhanced immunosuppressive regimen and additional safeguards for the non-ambulatory patient population while further analyzing the growing safety data alongside regulators.
ENVISION is a global, randomized, double-blind, placebo-controlled trial designed to enable regulators to confirm the safety and efficacy of ELEVIDYS in both older ambulatory and non-ambulatory individuals with DMD. The study forms a key piece of the accelerated approval process for non-ambulatory patients in the United States. The trial’s eventual resumption will be predicated upon regulators’ alignment with Sarepta’s updated study protocol and its improved safety framework.
Sarepta’s Commitment to Patients and Disease Community
“Our highest priority is the safety and well-being of the patients we serve. We are taking immediate, decisive, and responsible action to enable us to better understand and hopefully reduce the risk of acute liver failure in non-ambulatory Duchenne muscular dystrophy patients,” said Louise Rodino-Klapac, Ph.D., Sarepta’s Chief Scientific Officer and Head of Research and Development. “We are profoundly saddened by the death of a second patient and wish to extend our heartfelt condolences to their family and care team during this incredibly difficult time.”
Duchenne muscular dystrophy is a relentless and devastating disease — a condition that profoundly impacts not only the lives of those affected but their families’ futures. With more than 900 individuals treated with ELEVIDYS to date, there’s a strong understanding within the community that many view this therapy as a beacon of hope. Sarepta is honoring that hope by employing rigorous scientific discipline, a deep understanding of the disease, and a strong collaboration with regulators and expert stakeholders to maximize its safety profile while retaining its potential for delivering life-changing benefits.
Continuing Commitment to Long-Term Safety and Disease Modification
Sarepta maintains its firm and ongoing commitment to understanding the long-term safety profile of ELEVIDYS and to employing the highest standards of scientific rigor in its approach. The two cases of acute liver failure will aid regulators, clinicians, and the company in developing a more comprehensive understanding of the mechanisms underlying AAV-related liver complications.
While elevations in liver enzyme values are recognized as a class-related side effect with adeno-associated virus (AAV)-based gene therapy, the exact mechanisms that contribute to these abnormalities remain unclear. Currently, there is a growing body of data suggesting these events are driven by a complex adaptive immune response — a phenomenon that might be influenced by numerous factors, including the patient’s health, disease progression, and their own unique biology.
Sarepta plans to collaborate closely with regulators and expert advisors to incorporate these learnings into its prescribing information and label, reflecting both the potential risks and the strategies to manage them safely. The ultimate aim is to enable patients to realize the maximum possible benefits from this new and innovative therapy while minimizing or avoiding harm.
Sarepta will provide additional updates to regulators, health care providers, and the Duchenne community as its understanding evolves and its safety measures are implemented.
