Delandistrogene moxeparvovec (recombinant)

Class
Gene therapy
Subclass
Micro-dystrophin transgene
Substance name
Delandistrogene moxeparvovec, delandistrogene moxeparvovec-rokl
Brand names
Elevidys®
Common formulations
Suspension for intravenous infusion
Dosage and administration
Adults patients
Treatment of Duchenne muscular dystrophy
Weight < 70 kg
•
1.33×10¹⁴ vg/kg IV once, at a rate of < 10 mL/kg/hr
Indications for use
Labeled indications
Adults
•
Treatment of Duchenne muscular dystrophy
Safety risks
Contraindications
Anti-AAVrh74 antibodies
•
Obtain baseline testing for the presence of anti-AAVrh74 total binding antibodies before treatment. Do not use delandistrogene moxeparvovec in patients with elevated anti-AAVrh74 total binding antibody titers (≥ 1:400).
Deletion in exon 8 and/or exon 9 in the DMD gene
Moderate-to-severe LVEF impairment
•
Use caution in patients with mild LVEF impairment.
Warnings and precautions
Acute liver injury
•
Maintain a high level of suspicion, as delandistrogene moxeparvovec has been associated with an increased risk of acute serious liver injury, usually observed within 8 weeks of administration. Assess liver function (clinical assessment, GGT, and TBIL) before treatment and weekly for the first 3 months after administration. Continue monitoring if clinically indicated, until results are unremarkable. Increase peri-infusion corticosteroid dose to 2 mg/kg/day in patients receiving 1 mg/kg/day, and to 2.5 mg/kg/day in patients receiving 1.5 mg/kg/day.
Decreased platelet count
•
Maintain a high level of suspicion, as delandistrogene moxeparvovec has been associated with an increased risk of thrombocytopenia, usually observed within 2 weeks of administration. Obtain platelet counts before treatment and weekly for the first 2 weeks. Continue monitoring if clinically indicated.
Immune response
•
Maintain a high level of suspicion, as delandistrogene moxeparvovec has been associated with an increased risk of serious systemic immune response. Administer corticosteroids starting 1 day before infusion and continue for at least 60 days after the infusion, unless earlier tapering is clinically indicated, to reduce the risk of an immune response. Start at 1 mg/kg/day 1 day before infusion and continue the baseline dose in patients on daily or intermittent corticosteroids. Start at 1 mg/kg/day 1 day before infusion (taken on days without high-dose corticosteroid treatment) and continue baseline dose in patients on high-dose corticosteroids for 2 days per week. Start at 1.5 mg/kg/day 1 week before infusion in patients not on corticosteroids. Maximum dose of 60 mg per day (prednisone equivalent).
•
Postpone treatment in patients with concurrent infections until the infection resolves.
Immune-mediated myositis
•
Use caution in patients with DMD gene mutations in exons 1-17 and/or exons 59-71.
Infusion-related reactions
•
Maintain a high level of suspicion, as delandistrogene moxeparvovec has been associated with an increased risk of infusion-related reactions, including hypersensitivity reactions and anaphylaxis. Closely monitor patients during and for at least 3 hours after infusion. Consider slowing or wittholding infusion if an infusion-related reaction occurs, depending on severity. Consider restarting infusion at a lower rate after symptoms resolve. Discontinue infusion in case of anaphylaxis.
Myocarditis
•
Maintain a high level of suspicion, as delandistrogene moxeparvovec has been associated with an increased risk of acute serious myocarditis and troponin I elevations. Assess troponin I before treatment and weekly for the first month after administration. Continue monitoring if clinically indicated.
Specific populations
Renal impairment
eGFR 0-90 mL/min/1.73 m²
•
No guidance available.
Renal replacement therapy
Any modality
•
No guidance available.
Hepatic impairment
Acute or decompensated chronic liver disease
•
Postpone until resolved.
Any severity
•
Use with caution. Monitor for acute liver injury. Increase peri-infusion corticosteroid dose to 2 mg/kg/day in patients receiving 1 mg/kg/day and to 2.5 mg/kg/day in patients receiving 1.5 mg/kg/day if liver function abnormalities develop after delandistrogene moxeparvovec administration.
Pregnancy and breastfeeding
Pregnancy
All trimesters
•
Not intended for use in pregnant females.
Breastfeeding
Little information available on breastfeeding safety.
Unknown amount excreted in breastmilk.
Unknown drug levels in breastfed infants.
Adverse reactions
Very common > 10%
•
↑ serum transaminases, ↑ serum gamma-glutamyltransferase, ↑ liver enzymes, hepatotoxicity, ↑ serum TBIL, fever, nausea, vomiting
Common 1-10%
•
↓ platelet count
Unknown frequency
•
Anaphylaxis, immune-mediated myositis, myocarditis, infusion-related reactions
Interactions
Drug(s)
Check Interactions
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