MECHANISM OF ACTION — Delandistrogene moxeparvovec is a nonreplicating, recombinant AAV vector-based therapy that delivers a transgene encoding microdystrophin protein, a shortened protein that contains selected domains of the dystrophin protein expressed in normal muscle cells.

CLINICAL STUDIES — FDA approval of the expanded indications were based on the results of earlier trials in ambulatory patients 4-7 years old and an openlabel trial in patients ≥3 years old with DMD. Patients who received a single IV infusion of delandistrogene moxeparvovec demonstrated increased expression of microdystrophin protein in skeletal muscle cells, a surrogate endpoint that is considered likely to predict clinical benefit in both ambulatory and nonambulatory patients. In one of the trials, changes were also observed in three secondary efficacy endpoints: time to rise from the floor, 10- meter walk/run, and time to ascend 4 steps. A double-blind, placebo-controlled trial (ENVISION) in nonambulatory patients with no age restrictions and older ambulatory patients (8-17 years old) is underway.2

ADVERSE EFFECTS — Acute serious liver injury has been reported with delandistrogene moxeparvovec. Immunemediated myositis can occur, particularly in patients with deletions in exons 1-17 and/or exons 59-71 in the DMD gene. Nausea, vomiting, fever, thrombocytopenia, and myocarditis have also been reported.

DOSAGE AND COST — Elevidys is administered as a one-time IV infusion over 1-2 hours. It is contraindicated for use in patients with any deletion in exon 8 and/or exon 9 in the DMD gene. The wholesale acquisition cost of one dose of Elevidys is $3.2 million.3

CONCLUSION — The adeno-associated virus (AAV) vector-based gene therapy delandistrogene moxeparvovec (Elevidys) has received approval for treatment of Duchenne muscular dystrophy (DMD) in ambulatory and nonambulatory patients ≥4 years old who have a confirmed mutation in the DMD gene. Continued approval of Elevidys for use in nonambulatory patients is contingent on the results of an ongoing trial. The expanded approval now makes the very expensive gene therapy available to children and young men with DMD.