Written By: Pragati Ekamalli (B.Pharm)
Reviewed By: Vikas Londhe M.Pharm (Pharmacology)
In a groundbreaking step forward for genetic medicine, Japan has become the first country in the world to approve the use of Elevidys (delandistrogene moxeparvovec), a gene therapy created by Sarepta Therapeutics, for children under 4 years old diagnosed with Duchenne muscular dystrophy (DMD). DMD is a rare and life-threatening genetic disorder that leads to the progressive weakening and loss of muscle function, typically appearing in early childhood and worsening over time. Elevidys works by delivering a modified gene to help produce a version of the dystrophin protein, which is missing or defective in children with DMD. This approval represents a major milestone in the global effort to treat genetic disorders and could bring new hope to families affected by DMD. It also highlights Japan’s leadership in adopting cutting-edge medical treatments that may slow disease progression and improve quality of life for young patients.
Understanding Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a rare, inherited disorder that mainly affects boys due to its X-linked pattern of inheritance, meaning the faulty gene is carried on the X chromosome. The condition results from mutations in the DMD gene, which is responsible for producing dystrophin a protein critical for maintaining the strength and stability of muscle fibers. In the absence of functional dystrophin, muscles are unable to protect themselves from everyday stress, leading to ongoing damage, muscle fibres breakdown, and replacement by fat and scar tissue. Symptoms usually begin in early childhood, often with difficulty walking, running, or climbing stairs. As the disease progresses, most affected children lose their ability to walk by the age of 12 to 14. In later stages, DMD can lead to serious complications involving the heart and lungs, often reducing life expectancy into the twenties or thirties without advanced medical care.
Understanding Dystrophin Protein
Dystrophin is large structural protein (427kDa) present in cytoplasmic face of the sarcolemma. Dystrophin protein plays a crucial role in maintaining the integrity and function of muscle cells including skeletal muscle and cardiac muscle.
Dystrophin is act like an anchor which link internal cytoskeleton of a muscle fibre to the surrounding extracellular matrix by dystrophin-glycoprotein complex. This complex stabilizes muscle fibre during contraction. Dystrophin protein is coded with DMD gene on X-Chromosome and it is one of the largest human genes. Any mutation or deletion of DMD genes affects the dystrophin protein production, either less or completely diminished.
Elevidys: A Novel Gene Therapy Approach
Elevidys is an innovative gene therapy that uses an adeno-associated virus (AAV) as a delivery system to transport genetic material into the body. Specifically designed for Duchenne muscular dystrophy (DMD), Elevidys delivers a shortened but functional version of the dystrophin gene, called micro-dystrophin, directly into muscle cells. Although smaller than the full-length gene, micro-dystrophin includes the critical domains needed for the protein to support muscle fibre structure and function. By enabling cells to produce this essential protein, Elevidys targets the root cause of DMD — the absence of functional dystrophin. Administered as a single intravenous infusion, this therapy offers the promise of a one-time treatment that may slow disease progression and improve muscle strength, potentially transforming the standard of care for children living with DMD.
Japan’s Regulatory Approval
On August 14, 2024, Chugai Pharmaceutical Co., Ltd., a member of the Roche Group, submitted a regulatory application to Japan’s Ministry of Health, Labour and Welfare (MHLW) seeking approval for Elevidys, a gene therapy for Duchenne muscular dystrophy (DMD). The application specifically targeted ambulatory boys aged 3 to 7 years who do not have deletions in exons 8 and/or 9 of the DMD gene and who are not immune to the AAVrh74 viral vector used to deliver the treatment. This submission was supported by data from the global Phase III EMBARK study, which evaluated the safety and effectiveness of Elevidys. The trial did not meet its primary endpoint improving motor function as measured by the North Star Ambulatory Assessment (NSAA), however clinically meaningful benefits were observed in key secondary outcomes, including faster time to rise from the floor and improved 10-meter walk speed. Despite the mixed results, Japan’s MHLW granted priority review to the application and ultimately approved Elevidys for use in children less than 4 years of age. With this decision, Japan became the first country to authorize Elevidys for this younger age group, reflecting its proactive approach to approving innovative therapies for rare and serious diseases like DMD. This landmark approval offers new hope for patients and families affected by this devastating condition.
Global Context
Before Japan’s historic approval, the U.S. Food and Drug Administration (FDA) granted Elevidys accelerated approval in June 2023 for ambulatory children aged 4 through 5 years with Duchenne muscular dystrophy (DMD). The FDA’s decision was based on evidence that the therapy successfully prompted the production of micro-dystrophin, the shortened version of the dystrophin protein essential for muscle health. However, this approval was conditional, with continued authorization depending on the confirmation of meaningful clinical benefits in ongoing follow-up trials. Japan’s more inclusive approval for children under 4 years old not only marks a significant expansion of access to this gene therapy but also sets a global precedent. It signals to other regulatory agencies the potential value of early intervention in DMD. As new clinical data emerges and confirmatory studies continue, more countries may follow suit, potentially reshaping the global treatment landscape for this devastating disease and offering hope for earlier and more effective management of DMD in young patients.
Conclusion
The approval of Elevidys in Japan for children younger than 4 years of age marks a major breakthrough in the treatment of Duchenne muscular dystrophy (DMD). Unlike traditional therapies that mainly manage symptoms, Elevidys directly targets the genetic root of the disease by introducing a functional version of the dystrophin gene. This approach offers the potential not just to slow the progression of muscle degeneration, but to meaningfully alter the course of the disease, particularly when administered early in life. The decision by Japan’s health authorities highlights the critical role of early intervention and paves the way for improving long-term outcomes for children affected by DMD. Moreover, this milestone emphasizes the value of ongoing scientific research, clinical trials, and international collaboration in developing transformative therapies for rare and life-threatening conditions.
References
1. Sarepta Therapeutics Announces Approval in Japan of ELEVIDYS, a Gene Therapy to Treat Duchenne Muscular Dystrophy, 13 May 2025, Sarepta Therapeutics https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-approval-japan-elevidys-gene
2. A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD) (EMBARK), NCT05096221, ClinicalTrials.gov, available from https://clinicaltrials.gov/study/NCT05096221
3. Roche announces new results from EMBARK demonstrating significant sustained benefits of Elevidys in ambulatory individuals with Duchenne muscular dystrophy (DMD), 27 January 2025, https://www.roche.com/media/releases/med-cor-2025-01-27
4. Gao QQ, McNally EM. The Dystrophin Complex: Structure, Function, and Implications for Therapy. Compr Physiol. 2015 Jul 1; 5(3):1223-39. Doi: 10.1002/cphy.c140048. PMID: 26140716; PMCID: PMC4767260.
5. Venugopal V, Pavlakis S. Duchenne Muscular Dystrophy. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482346/
6. Chugai Receives Regulatory Approval for “ELEVIDYS” as a Gene Therapy Product for Duchenne Muscular Dystrophy in Japan, 13 May 2025, Chugai Pharmaceuticals,https://www.chugaipharm.co.jp/english/news/detail/20250513181500_1160.html
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