Consensus Guidelines Aim to Optimize DMD Gene Therapy Delivery

Multidisciplinary coordination is of the utmost importance to ensure appropriate gene therapy administration, and consensus recommendations presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference aimed to provide practical guidelines to supplement existing frameworks for gene therapy treatment in Duchenne muscular dystrophy (DMD).1

Gene therapies have changed the treatment landscape for inherited neurological conditions in recent years, with FDA approvals in DMD and spinal muscular atrophy providing options with the potential to slow disease progression. Since its initial FDA approval in 2023 for ambulatory patients aged 4 to 5 years, delandistrogene moxeparvovec-rokl (Elevidys; Sarepta Therapeutics) has also been approved for ambulatory and nonambulatory patients aged 4 years and older.2

The consensus guidelines aim to provide practical guidance for institutions administering gene therapy in a commercial or trial setting. | Image credit: CrazyJuke - stock.adobe.com

As gene therapies become increasingly accessible to eligible patients, several factors must be considered by centers planning to administer them to patients.1 The recommendations are intended to add to existing regulatory and clinical frameworks, aiming to ensure patient-centered care, the authors explained. They break the process down into 4 categories: institutional readiness, patient selection, pre-dosing activities, and postinfusion monitoring.

Institutional Readiness and Patient Selection for DMD Gene Therapy

“Delivery of gene therapy involves clinical expertise for managing standard-of-care for the underlying disorder and potential adverse effects of treatment, and institutional readiness in multiple areas, including insurance authorizations, purchasing and contracting, pharmacy, and others," the abstract stated.

The guidelines provide several benchmarks to gauge institutional readiness for DMD gene therapy administration, with the first being a care team that has extensive experience treating patients with DMD in the acute and chronic settings. A multidisciplinary care team with expertise in gene therapy, including a neurologist and/or physiatrist, cardiologist, hepatologist, pulmonologist, specialty nurse or nurse navigator, and immunologist, is also important.

Specialists to manage potential adverse events associated with gene therapy should also be available, including an emergency medicine team, intensivists, a nephrologist, geneticist, gastroenterologist, hematologist, and an ethicist, according to the guidelines. Additionally, a plan for communicating with and educating a patient’s primary care physician should be in place. There should also be staff and resources dedicated to obtaining insurance approvals and appeals for coverage quickly.

Rare complications can arise, and it is crucial to have monitoring plans and mitigation strategies for such complications as infusion reactions, troponinemia, myocarditis, myositis, and hepatotoxicity. Access to intensive care unit or critical care unit beds is also recommended.

Regarding patient selection, a crucial consideration is the cardiac and pulmonary status of the patient receiving gene therapy, as well as eligibility based on the FDA-approved indication or clinical trial protocol, according to the guidelines. Patients should have reasonable cardiac and pulmonary health to minimize the risk of serious adverse events, although the decision should be tailored to each patient. Currently, literature to guide decision-making is limited, the authors noted. However, the consensus is to wait for additional data on the treatment of patients with a left ventricular ejection fraction of less than 40%.

“The decision to treat with gene therapy should be a decision made between the patient, their caregivers, and the care team based on informed consent and assent covering the known risks and benefits, as well as the life-threatening, irreversible nature of DMD,” the authors wrote.

Pre-Infusion Activities and Post-Infusion Monitoring

Prior to dosing patients with gene therapy for DMD, there are several important steps outlined in the guidelines, including the collection of functional outcome measures at regular intervals before and 6 months after treatment, cardiac monitoring to compare pre- and post-dosing cardiac health, and keeping patients on stable doses of all medications except givinostat.

The patient’s family should also be engaged in discussions about therapeutic misconceptions, short- and long-term monitoring plans, an emergency plan with on-call physician information, and when emergency care is needed. Institutional communication around laboratory results and the definition of clinically significant results is also important, as is discussion of the need for access to tissues or autopsy materials.

After infusion, monitoring in the short and long term must be in line with the FDA-approved label or clinical trial protocol if the product is investigational. Key steps in cases where laboratory abnormalities or observed side effects are detected include assessing any patient with nausea, vomiting, chest pain, palpitations, abdominal pain, severe fatigue, or rapid breathing. Any symptoms of myositis might also necessitate additional immunomodulatory treatment in addition to corticosteroids, the guidelines noted. They also outline processes for increased troponin levels, which may warrant further investigation if they meet certain thresholds.

“The administration of gene therapy requires specialized clinical infrastructure, including multidisciplinary coordination across prescribing teams, nursing, laboratory medicine, finance, and infusion centers. Given these complexities, consensus-based best practice recommendations are crucial as gene therapy becomes integrated in DMD clinical care," the authors wrote. "This work, led by expert clinicians through the Muscular Dystrophy Association (MDA) and Parent Project Muscular Dystrophy (PPMD), aims to provide practical guidance for institutions administering gene therapy in a commercial or trial setting.”

References

1. Wolff J, Capocci N, Hesterlee S, et al. Consensus recommendations and considerations for the delivery and long-term monitoring of gene transfer therapy in Duchenne muscular dystrophy. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-18, 2025; Dallas, TX. Poster P66.
2. Shaw M. FDA grants 2 approvals to delandistrogene moxeparvovec for DMD. The American Journal of Managed Care®. June 20, 2024. Accessed April 18, 2025. https://www.ajmc.com/view/fda-grants-2-approvals-to-delandistrogene-moxeparvovec-for-dmd