In a report released May 14 in Neurology, the AAN Guidelines Subcommittee cautions both proponents and detractors of the FDA-approved treatment for Duchenne muscular dystrophy (DMD), Elevidys gene therapy, that additional clinical trials and empirical data are required to elucidate the cure’s long-term advantages and disadvantages.
The new “Evidence in Focus” report from the AAN Subcommittee reviews the available data, poses issues that the committee believes should be addressed, and offers suggestions to guide future studies.
After the death of a 16-year-old patient with DMD, the efficacy of delandistrogene moxeparvovec (Elevidys), which was given full approval by the US Food and Drug Administration in 2024 for ambulatory individuals, was once again questioned. The patient passed away from severe liver failure following the therapy, according to a study released earlier this year by the drug’s developer, Sarepta Therapeutics. – Read More: 16 Years Old Boy Death After Elevidys –
In June 2023, the FDA gave the gene therapy expedited approval for ambulatory patients aged 4 to 5. The review committee members at the time argued over the application’s clinical benefit and could not agree on whether it reached the regulatory bar for approval.
According to the AAN article, an FDA administrator overruled the review committee’s conclusion since a subgroup of patients had some improvement at one year following therapy as compared to a placebo. Based on additional information provided by the firm, the FDA approved the medicine in full for ambulatory patients aged 4 and over in June 2024 and expedited approval for non-ambulatory patients aged 4 and over.
Some detractors have claimed that clinical trials of the very costly gene therapy have shown very few, if any, advantages since the medication was approved in 2023 under the FDA’s expedited clearance process. Amid worries that the main functional motor outcome measure, the change in the North Star Ambulatory Assessment score (NSAA), had not been met in clinical testing, the FDA even appeared to change its mind about approving the first-in-class treatment.
Safety Concerns Over Elevidys Gene Therapy
According to the report, “providers should be aware of the limitations of the treatment and the need to monitor for immune-related side effects including myocarditis, liver injury, and thrombocytopenia, which may require expanded clinical infrastructure, as the drug may now be actively prescribed in the US and other countries after FDA approval.” It stated that additional information anticipated from clinical trials and non-trial patient use of the medication “will be essential to establish short- and long-term effectiveness” and to resolve any unresolved safety concerns.
The best time to administer therapy, which employs an adenovirus-associated vector, is a crucial question. Patients with ambulatory and non-ambulatory DMD who are 4 years of age or older and have a verified mutation in the dystrophin gene—with the exception of those who have deletions that include exons 8–9—are eligible for single-dose gene therapy. It would be advantageous to treat patients as early in life as feasible, when disease has less of an effect on the muscle. However, other doubters contend that receiving the gene therapy treatment too soon could prevent the patient from receiving a future, more successful gene therapy.
DMD experts and a patient advocate were part of the author panel that was chosen by the AAN Guidelines Subcommittee to assess the gene therapy evidence. Generally speaking, AAN’s Evidence in Focus reports assess the quality of the evidence and promote dialogue regarding the proper application of the therapy using a condensed form of the AAN guidelines methodology. There are no particular clinical care recommendations in the papers.
Elevidys $2.9 million price tag is also a major worry
According to main author Maryam Oskoui, MD, FAAN, a clinical research scientist at McGill University in Montreal and a professor of pediatrics, neurology, and neurosurgery, “there is no recommendation that you should do this or you should not do this.” Although patients and their families inquire about it, she stated that gene therapy for DMD is not yet available in Canada.
The gene therapy for DMD does not appear to have generated as much excitement as the gene therapy for spinal muscular atrophy, according to senior author James Dowling, MD, professor in the departments of neurology and genetics and director of the Penn Neurogenetics Therapy Center at the University of Pennsylvania.
Dr. Dowling stated, “I recognize the general weariness the [DMD] community is experiencing due to a medication that didn’t have the desired effect.”
More than 800 DMD patients have received the treatment in clinical trials or as a prescription, according to Sarepta Therapeutics. According to Lisa Borland, senior vice president for global medical affairs at the firm, 90 patients aged 12 or older and patients older up to 26 have received doses in the non-trial context.
In the upcoming months, longer-term data in ambulatory patients, confirmatory phase 3 data in non-ambulatory patients (ENVISION), and real-world evidence will be added to the substantial and expanding body of evidence supporting efficacy, according to Borland. The business expects that the ENVISION results, which are anticipated in 2027, will result in the complete approval of gene therapy for patients who are not ambulatory, she added.
Updated on 15th June 2025: Sarepta informa del segundo caso de muerte por insuficiencia hepática tras su tratamiento de terapia génica
Assessing the Evidence
A database assessment of published research on the delandistrogene moxeparvovec served as the foundation for the AAN’s new “Evidence in Focus.” Four of the six clinical trials that were found had peer-reviewed data available. 134 boys, 128 of whom were ambulatory and between the ages of 4 and 8, had drug data available from the four investigations (two Class 1 and 2, Class3). The NSAA, a 17-item assessment of ambulatory functions, served as the main outcome in the four trials. Each task was scored on a scale of 0 (unable to do), 1 (able to execute but struggled or required assistance), or 2 (able to perform). Walking, running, and getting up off the ground are among the activities.
Leer más: Revisión de ensayos clínicos de la terapia génica Elevidys: ¿Vale la pena el costo de la Elevidys?
According to the review, neither of the two Class I studies achieved the primary functional motor endpoint as determined by the change in the NSAA score.
Conclusión
Although the North Star Assessment score (NSAA) in children treated with Elevidys gene therapy was lower than expected, the treatment’s marketing price of 2.9 million USD continues to worry patients and their families.
However, the Sarepta share price, which was 101.35 USD on March 17, 2025, before the first death, fell to 20.77 USD on June 19, 2025, after the announcement of the second death.
Más información: Preguntas frecuentes sobre Elevidys
