Profile
General Information
Elevidys (delandistrogene moxeparvovec-rokl) is an adeno-associated virus based gene therapy.
Elevidys is specifically indicated for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene.
Dosing/Administration
Elevidys is supplied as a suspension for intravenous infusion.
Prior to infusion:
- Select patients for treatment with Elevidys with anti-AAVrh74 total binding antibody titers <1:400
- Postpone in patients with concurrent infections until the infection has resolved.
- Assess liver function, platelet counts and troponin-I before Elevidys infusion.
- One day prior to infusion, initiate a corticosteroid regimen for a minimum of 60 days. Recommend modifying corticosteroid dose for patients with liver function abnormalities.
The recommended dose of Elevidys is 1.33 × 1014 vector genomes per kilogram (vg/kg) of body weight (or 10 mL/kg body weight).
Calculate the dose as follows: Elevidys dose (in mL) = patient body weight (in kilogram) x 10
- The multiplication factor 10 represents the per kilogram dose (1.33 × 1014 vg/kg) divided by the amount of vector genome copies per mL of the Elevidys suspension (1.33 × 1013 vg/mL).
Number of Elevidys vials needed = Elevidys dose (in mL) divided by 10 (round to the nearest number of vials).
- Example: Calculation of volume needed for a 19.6 kg patient 19.6 kg × 10 = 196 mL Number of Elevidys vials needed = 196 divided by 10, rounded to the nearest number of vials = 20 vials
Administer as an intravenous infusion over 1-2 hours. Infuse at a
rate of less than 10 mL/kg/hour
Mechanism of Action
Elevidys 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.
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.
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 microdystrophin expression in skeletal muscle.
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.
Side Effects
Adverse effects associated with the use of Elevidys may include, but are not limited to, the following:
- vomiting and nausea
- liver function test increased
- pyrexia
- thrombocytopenia
Patients given Elevidys may also be at risk for severe immune-mediated myositis. Additionally, myocarditis and elevations of troponin-I have been observed following use of Elevidys in clinical trials.
Clinical Trial Results
This indication is approved under accelerated approval based on expression of Elevidys microdystrophin in skeletal muscle observed in patients treated with Elevidy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Accelerated approval was based on data from a two part study. Individuals in part 1—which was randomized, double-blind, and placebo-controlled—were treated with either Elevidys or placebo and followed for 48 weeks. In part 2 of the study, individuals who received placebo during part 1 were treated with Elevidys, and individuals treated with Elevidys during part 1 received a placebo. All individuals were followed for an additional 48 weeks.
Elevidys increased the expression of the Elevidys micro-dystrophin protein observed in Elevidys-treated individuals aged 4 to 5 years with DMD. The FDA concluded that the data submitted by the applicant demonstrated that an increase in this surrogate endpoint (expression of Elevidys micro-dystrophin) is reasonably likely to predict clinical benefit in individuals 4 to 5 years of age with DMD who do not have significant pre-existing antibody titers against the AAV rh74 vector or have other contraindications based on the inclusion criteria of the clinical trials.