Elevidys is an adeno-associated virus vector-based gene therapy
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
Elevidys may be considered medically necessary if the conditions indicated below are met.
Elevidys may be considered investigational for all other indications.
Prior-Approval Requirements
Age 4 years of age or older at the time of infusion
Gender assigned at birth Male
Diagnosis
Patient must have the following:
Duchenne muscular dystrophy (DMD)
AND ALL the following:
1. Genetic confirmation of DMD
2. NO deletion in exons 1 to 17 and/or exons 59 to 71 in the DMD gene
3. Anti-AAVrh74 total binding antibody titers are <1:400
4. Prescriber agrees that patient will NOT be using concomitant anti-sense oligonucleotides post-administration
5. Prescribed by or in consultation with a neurologist specializing in DMD
6. Patient has not previously received gene therapy for DMD
Prior - Approval Limits
Quantity One infusion (only one PA approval for one infusion per lifetime)
J1413
Background
Elevidys (delandistrogene moxeparvovec-rokl) is the recombinant gene therapy product that is comprised of a non-replicating, recombinant, adeno-associated virus (AAV) serotype rh74 (AAVrh74) capsid and a ssDNA expression cassette flanked by inverted terminal repeats (ITRs) derived from AAV2. The cassette contains: 1) an MHCK7 gene regulatory component comprising a creatine kinase 7 promoter and an α-myosin heavy chain enhancer, and 2) the DNA transgene encoding the engineered Elevidys micro-dystrophin protein (1).
Vector/Capsid: Clinical and nonclinical studies have demonstrated AAVrh74 serotype transduction in skeletal muscle cells. Additionally, in nonclinical studies, AAVrh74 serotype transduction has been demonstrated in cardiac and diaphragm muscle cells (1).
Promoter: The MHCK7 promoter/enhancer drives transgene expression and has been shown in animal models to drive transgenic Elevidys micro-dystrophin protein expression predominantly in skeletal muscle (including diaphragm) and cardiac muscle. In clinical studies, muscle biopsy analyses have confirmed Elevidys micro-dystrophin expression in skeletal muscle (1).
Transgene: DMD is caused by a mutation in the DMD gene resulting in lack of functional dystrophin protein. Elevidys carries a transgene encoding a micro-dystrophin protein consisting of selected domains of dystrophin expressed in normal muscle cells (1).
Elevidys micro-dystrophin has been demonstrated to localize to the sarcolemma (1).
Regulatory Status
FDA-approved indication: Elevidys is an adeno-associated virus vector-based gene therapy indicated in individuals at least 4 years of age: (1)
• For the treatment of Duchenne muscular dystrophy (DMD) in patients who are ambulatory and have a confirmed mutation in the DMD gene
• For the treatment of DMD in patients who are non-ambulatory and have a confirmed mutation in the DMD gene.
Elevidys is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene (1).
Acute serious liver injury has been observed with Elevidys use. Monitor liver function before Elevidys infusion, and weekly for the first 3 months after infusion. Continue monitoring until results are unremarkable. If acute serious liver injury is suspected, a consultation with a specialist is recommended (1).
Patients with deletions in the DMD gene in exons 1 to 17 and/or exons 59 to 71 may be at risk for severe immune-mediated myositis reaction. Consider additional immunomodulatory treatment if symptoms of myositis occur (1).
Myocarditis and troponin-I elevations have been observed with Elevidys use. Monitor troponin-I before Elevidys infusion, and weekly for the first month after infusion (1).
Pre-existing immunity against AAVrh74 may occur. Perform baseline testing for presence of anti-AAVrh74 total binding antibodies prior to Elevidys administration (1).
The safety and effectiveness of Elevidys in patients less than 4 years of age and greater than 5 years of age have not been established (1).
References
1. Elevidys [package insert]. Cambridge, MA: Sarepta Therapeutics, Inc; August 2024.
Summary
Elevidys (delandistrogene moxeparvovec-rokl) is an adeno-associated virus vector-based gene therapy indicated for the treatment of ambulatory or non-ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. Elevidys is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene. Acute serious liver injury and myocarditis have been observed with Elevidys use. Immune-mediated myositis and pre-existing immunity against AAVrh74 may occur. The safety and effectiveness of Elevidys in patients less than 4 years of age and greater than 5 years of age have not been established (1).
Prior approval is required to ensure the safe, clinically appropriate, and cost-effective use of Elevidys while maintaining optimal therapeutic outcomes.
References
1. Elevidys [package insert]. Cambridge, MA: Sarepta Therapeutics, Inc; August 2024.
