Pre-, Postinfusion Protocol Recommendations for Delandistrogene Moxeparvovec Use in DMD

Investigators have come up with recommended clinical guidelines for the administration of delandistrogene moxeparvovec-rokl (Elevidys; Sarepta Therapeutics), a recombinant adeno-associated virus (rAAV)–based gene transfer therapy indicated to treat Duchenne muscular dystrophy (DMD) in ambulatory patients aged 4 to 5 years who have a confirmed mutation in the DMD gene. Their findings appear in a recent issue of Pediatric Neurology,¹ and they cover proposed protocols before and after the 1-time infusion.

Medical information and treatment guidelines

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The gene therapy was approved by the FDA on June 22, 2023,² and Sarepta recently filed supplemental data with the FDA seeking to expand the labeled indication by removing the age and ambulatory status restrictions.³ 

“Delandistrogene moxeparvovec is designed to compensate for the absence of functional dystrophin protein in DMD,” the authors wrote, “by delivering a transgene encoding delandistrogene moxeparvovec micro-dystrophin, an engineered dystrophin protein containing key functional domains of the wild-type protein.”

There are 9 recommendations altogether: 5 for the pre-infusion setting and 4 for the postinfusion settings. The investigators fashioned this guidance, meant to support health care professionals initiating the gene therapy, using data on 85 male patients from the Study 101 (NCT03375164; data cutoff, October 17, 2022), Study 102 (NCT03769116; data cutoff, October 3, 2022), and ENDEAVOR (Study 103; NCT04626674; data cutoff, September 19, 2022) trials. These data accounted for 183 patient-years, and their mean follow-up was 2.2 (0.5-4.8) years.

Prior to infusion, the authors recommend performing the following:

• Screen for anti–AAV-associated rhesus isolate serotype 74 (anti-AAVrh74): Because delandistrogene moxeparvovec is contraindicated in patients with elevated anti-AAVrh74 antibody titers, knowing these levels may help head off immune responses to the viral vector used to deliver delandistrogene moxeparvovec
• Assess liver function, platelet count, and troponin-I: This helps to establish baseline liver function
• Ensure vaccines are up-to-date in patients and avoid vaccine co-administration with infusion: This helps to prevent infection that may delay the gene treatment, such as those from live-attenuated vaccines (contraindicated in these settings)
• Initiate additional corticosteroid treatment the day before infusion, for those already on this treatment: This contributes to reducing the risk of an adverse immune response; clinicians should modify these regimens when abnormal liver function is present
• Postpone infusion in patients who have a current liver infection or acute disease: It’s important to resolve these events in patients currently on immunosuppression, such as corticosteroids

After infusion, the authors recommend these actions:

• Monitor liver function weekly for the first 3 months, until results are unremarkable: This includes a clinical exam, gamma-glutamyl transferase, and total bilirubin, to help detect potential acute serious liver injury
• Monitor troponin-I level weekly for the first month, and continue as needed: Elevated levels of this protein, only found in heart muscle cells, in the blood indicate heart muscle damage
• Measure platelets each of the first 2 weeks: This helps to establish any variances from the established baseline function continue as needed; elevated platelets increase clot risk and decreased platelets, infection
• Continue corticosteroids through 60 days at least: Maintenance helps to lower the risk of a potential adverse immune response following delandistrogene moxeparvovec infusion

“The safety profile in the delandistrogene moxeparvovec clinical development program has been consistent, monitorable, and manageable,” the study authors concluded. “These practical considerations of treatment are based on available clinical trial data and are intended to aid physicians treating patients with DMD.

References

1. Mendell JR, Proud C, ZaidmanPractical considerations for delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy. Pediatr Neurol. 2024;153:11-18. doi:10.1016/j.pediatrneurol.2024.01.003
2. Sarepta Therapeutics announces FDA Approval of Elevidys, the first gene therapy to treat Duchenne muscular dystrophy. Press release. Sarepta Therapeutics. June 22, 2023. Accessed February 5, 2024. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-fda-approval-elevidys-first-gene
3. Sarepta Therapeutics submits efficacy supplement to expand the Elevidys label to include Duchenne muscular dystrophy patients without restriction to age or ambulatory status. Press release. Sarepta Therapeutics. December 22, 2023. Accessed February 5, 2024. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-submits-efficacy-supplement-expand-elevidys