Roche Suspends Elevidys Dosing in Non-Ambulatory DMD Patients Amid Safety Concerns
Roche today announced a significant update to its dosing guidelines for Elevidys™ (delandistrogene moxeparvovec), following a careful reassessment of its benefit-risk profile in non-ambulatory patients with Duchenne muscular dystrophy (DMD). This update comes after two cases of fatal acute liver failure (ALF) were reported in non-ambulatory DMD patients who received Elevidys, a phenomenon that underscores the ongoing complexities and safety signals related to adeno-associated virus (AAV)-mediated gene therapy.
Effective immediately, Roche is halting the administration of Elevidys to non-ambulatory DMD patients in both commercial and clinical trial settings. Furthermore, enrollment and dosing for non-ambulatory patients in ongoing Elevidys trials will be paused until additional risk mitigation measures — for instance, employing appropriate immune modulatory treatments — are implemented in the study protocols. This decision forms a crucial step in ensuring patient safety while retaining the potential for Elevidys’ continued delivery to those who may still benefit from its mechanisms of action.
Roche is currently in close communication with health authorities, investigators, and prescribing physicians to enable a smooth and cautious adjustment in patient care following these updated guidelines. The aim is to make sure that all patients, whether currently participating in a trial or receiving commercial treatment, are kept safely and appropriately managed in light of the new information.
This policy change reflects a careful and exhaustive evaluation by Roche alongside regulators and scientific experts in the field of neuromuscular disorders. The two cases of fatal acute liver failure — both occurring in non-ambulatory DMD patients — highlight a previously recognized but rare and severe risk associated with Elevidys and other AAV-mediated treatments. Importantly, the new dosing restrictions do not apply to ambulatory DMD patients of any age; for these individuals, the benefit-risk profile for Elevidys is still considered favorable.
“We are deeply saddened by the two deaths related to acute liver failure in these young men,” said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development at Roche. “Patient safety is always our highest priority. Therefore, we have made the difficult but responsible decision to halt Elevidys treatment in non-ambulatory patients with immediate effect. Our team is currently investigating all related details alongside regulators and the scientific community to enable us to mitigate future risks while retaining the potential benefits for patients who may still be eligible for this treatment.”
Duchenne muscular dystrophy is a rare, X-linked, degenerative muscle disease predominantly affecting boys. It typically involves a dramatic and progressive deterioration of muscle strength, starting from the lower limbs in early childhood and extending upward, eventually affecting upper limb, lung, and heart muscle. The disease profoundly impacts the ability to walk and perform daily routines, with most patients becoming non-ambulatory by their teenage years. The condition typically further progresses to compromise respiratory and heart function, placing a heavy burden on both patients and their families.
DMD occurs in roughly 1 in 5,000 male births, making it a rare disease with limited treatment options. The two cases of fatal acute liver failure reported after Elevidys administration highlight a previously recognized but exceedingly rare and serious side effect. The two cases were both in non-ambulatory patients and represent a small portion — two cases out of a total of approximately 140 non-ambulatory patients who have been treated with Elevidys to date — but their significance cannot be disregarded in assessing the overall safety profile for the treatment in this population.
In response to the first case of fatal ALF, European regulators previously placed a temporary clinical hold on several Elevidys trials, including Study 104 (NCT06241950), Study 302 (ENVOL, NCT06128564), and Study 303 (ENVISION, NCT05310071). These holds remain in effect while regulators and study teams carefully investigate the event. Furthermore, outside of Europe, dosing will be paused immediately in the ENVISION trial, adding additional safeguards to protect trial participants.
Roche’s updated policy will also prohibit future commercial dosing for non-ambulatory DMD patients. This decision underscores a cautious approach to patient safety, reflecting both the serious nature of the adverse events and the ongoing uncertainty surrounding their mechanisms. Importantly, this policy change does not affect the treatment of ambulatory DMD patients, for whom Elevidys’ benefit-risk profile is still considered favorable.
Elevidys has previously been approved by regulators in eight Roche territories — Bahrain, Brazil, Israel, Japan, Kuwait, Oman, Qatar, and the UAE — for the treatment of DMD. The therapy is designed to enable the delivery of a functional micro-dystrophin directly to muscle cells, with the aim of slowing disease progression and improving muscle function. Elevidys utilizes adeno-associated virus vector technology, which is a powerful delivery platform but carries inherent risks related to the delivery process and the patient’s own immune response.
Roche entered into a global collaboration agreement with Sarepta Therapeutics in 2019 to commercialize Elevidys in markets outside the United States. The two companies collaborate closely on the ongoing clinical trials evaluating Elevidys’ safety, tolerability, and efficacy in DMD patients across a range of ages and disease severity. Roche is the sponsor for the ENVOL study, while Sarepta is responsible for all other trials in its portfolio.
While the new policy may delay the delivery of Elevidys to a subset of DMD patients, Roche and its collaborators remain fiercely committed to developing effective treatments for this aggressive disease. Scientists and regulators alike are currently investigating the mechanisms underlying these rare but catastrophic events in the hopes of reducing future risk while retaining the potential for patients to realize the substantial benefits Elevidys may provide.
Patient safety, rigorous scientific oversight, and careful consideration of both the potential benefits and the associated risks will guide all future decisions related to Elevidys’ administration. The ultimate aim is to enable patients with DMD and their families to enjoy a greater degree of independence, functionality, and improved quality of life — safely and responsibly.
