delandistrogene moxeparvovec (Rx)

Brand and Other Names:Elevidys, delandistrogene moxeparvovec-rokl

Dosing & Uses

AdultPediatric

See pediatric dosing

Dosage Forms & Strengths

suspension for IV infusion

  • 1.33 x 1013 vector genomes (vg)/mL

Duchenne Muscular Dystrophy

Indicated for Duchenne muscular dystrophy (DMD) in ambulatory pediatric patients aged 4-5 years with a confirmed mutation in the DMD gene

1.33 x 1014 vector genomes (vg)/kg of body weight (or 10 mL/kg)

Calculate dose

  • Dose (in mL) = patient body weight (in kg) x 10
  • The multiplication factor 10 represents the per kilogram dose (1.33 x 1014 vg/kg) divided by the amount of vector genome copies per mL of the suspension (1.33 x 1013 vg/mL)
  • Number of vials needed = dose (in mL) divided by 10 (round to nearest number of vials)
  • Example: Calculation of volume for 19.6 kg patient
    • 19.6 kg x 10 = 196 mL
    • Number of vials needed = 196 divided by 10, rounded to nearest number of vials = 20 vials

Pre- and post-infusion corticosteroid dosing

  • Not to exceed prednisone (or prednisone equivalent) total daily dose (TDD) of 60 mg/day
  • Deflazacort is not recommended for use as a peri-infusion corticosteroid
  • Baseline corticosteroid use daily or intermittent
    • Start 1 day before infusion
    • 1 mg/kg/day (and continue baseline dose)
  • Baseline high-dose corticosteroids 2 days/wk
    • Start 1 day before infusion
    • 1 mg/kg/day on days without high-dose corticosteroid treatment (and continue baseline dose)
  • Not on corticosteroids
    • Start 1 week before infusion
    • 1.5 mg/kg day

Recommended corticosteroid regimen dose modification for liver function abnormalities following infusion

  • GGT ≥150 U/L and/or other clinically significant liver function abnormalities (eg, total bilirubin >2 x ULN) following infusion; for GGT or bilirubin elevations that do not respond to these oral corticosteroid increases, IV bolus corticosteroids may be considered; deflazacort is not recommended for use as a peri-infusion corticosteroid
  • Not to exceed prednisone (or prednisone equivalent) TDD of 120 mg/day
  • Peri-infusion baseline + 1 mg/kg/day: Increase to 2 mg/kg/day (and continue baseline dose)
  • Peri-infusion baseline + 1 mg/kg/day (on days without high-dose corticosteroid): Increase to 2 mg/kg/day on days without high-dose corticosteroids
  • Peri-infusion 1.5 mg/kg/day: Increase to 2.5 mg/kg/day

Dosage Modifications

Hepatic impairment

  • Safety and efficacy in patients with hepatic impairment or elevated GGT not studied
  • Postpone administration in patients with acute liver disease until resolved or controlled
  • Carefully consider use in patients with preexisting liver impairment or chronic hepatic viral infection; these patients may be at increased risk of acute serious liver injury

Dosing Considerations

Patient selection

  • Select patients for treatment with anti-AAVrh74 total binding antibody titers <1:400
  • An FDA-authorized test for detection of AAVrh74 total binding antibodies is not currently available; current available tests may vary in accuracy and design

Monitoring

  • In view of the increased risk of serious systemic immune response, postpone administration in patients with infections until completely resolved
  • Before administration, perform liver enzyme testing, then monitor liver function (clinical exam, GGT, and total bilirubin) weekly x 3 months following infusion
  • Measure baseline anti-AAVrh74 antibody titers using a total binding antibody enzyme-linked immunosorbent assay (ELISA); not recommended if titer ≥1:400
  • Obtain platelet count
  • Monitor troponin-I before infusion and weekly for first month following infusion
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Interactions

Interaction Checker

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                Monitor Closely (18)

                • diphtheria & tetanus toxoids

                  delandistrogene moxeparvovec, diphtheria & tetanus toxoids. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • diphtheria & tetanus toxoids/ acellular pertussis vaccine

                  delandistrogene moxeparvovec, diphtheria & tetanus toxoids/ acellular pertussis vaccine. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine

                  delandistrogene moxeparvovec, diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • haemophilus influenzae type b vaccine

                  delandistrogene moxeparvovec, haemophilus influenzae type b vaccine. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • hepatitis b vaccine

                  delandistrogene moxeparvovec, hepatitis b vaccine. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • influenza virus vaccine quadrivalent

                  delandistrogene moxeparvovec, influenza virus vaccine quadrivalent. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • influenza virus vaccine quadrivalent, cell-cultured

                  delandistrogene moxeparvovec, influenza virus vaccine quadrivalent, cell-cultured. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • measles mumps and rubella vaccine, live

                  delandistrogene moxeparvovec, measles mumps and rubella vaccine, live. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • meningococcal A C Y and W polysaccharide tetanus toxoid conjugate vaccine

                  delandistrogene moxeparvovec, meningococcal A C Y and W polysaccharide tetanus toxoid conjugate vaccine. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • meningococcal C and Y/haemophilus influenza type B vaccine

                  delandistrogene moxeparvovec, meningococcal C and Y/haemophilus influenza type B vaccine. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • pneumococcal vaccine 13-valent

                  delandistrogene moxeparvovec, pneumococcal vaccine 13-valent. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • pneumococcal vaccine 15-valent

                  delandistrogene moxeparvovec, pneumococcal vaccine 15-valent. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • pneumococcal vaccine 20-valent

                  delandistrogene moxeparvovec, pneumococcal vaccine 20-valent. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • poliovirus vaccine inactivated

                  delandistrogene moxeparvovec, poliovirus vaccine inactivated. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • rotavirus oral vaccine, live

                  delandistrogene moxeparvovec, rotavirus oral vaccine, live. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • tetanus & reduced diphtheria toxoids/ acellular pertussis vaccine

                  delandistrogene moxeparvovec, tetanus & reduced diphtheria toxoids/ acellular pertussis vaccine. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • varicella virus vaccine live

                  delandistrogene moxeparvovec, varicella virus vaccine live. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                • varicella zoster immune globulin, human

                  delandistrogene moxeparvovec, varicella zoster immune globulin, human. Other (see comment). Use Caution/Monitor. Comment: Consider patient vaccination status before initiating corticosteroid regimen required before delandistrogene moxeparvovec administration. If possible, ensure patients are current with all immunizations according to immunization guidelines. Complete vaccinations at least 4 weeks before starting corticosteroid regimen. High-dose or long-term corticosteroids may decrease immungenicity of vaccines.

                Minor (0)

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                  Adverse Effects

                  >10%

                  Vomiting (61-65%)

                  Nausea (35-40%)

                  Liver function test vaules increased (25-37%)

                  Pyrexia (20-24%)

                  Thrombocytopenia (12%)

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                  Warnings

                  Contraindications

                  Patients with any deletion in exon 8 and/or exon 9 in DMD gene

                  Cautions

                  Acute serious liver injury

                  • Acute serious liver injury observed; administration may result in elevated liver enzymes (eg, GGT, ALT) and total bilirubin, typically seen within 8 weeks; if suspected, consultation with a specialist is recommended
                  • Patients with preexisting liver impairment, chronic hepatic condition, or acute liver disease (eg, acute hepatic viral infection) may be at higher risk of acute serious liver injury
                  • Postpone administration in patients with acute liver disease until resolved or controlled
                  • Patients with hepatic impairment, acute liver disease, chronic hepatic condition, or elevated GGT have not been studied in clinical trials
                  • In clinical studies, liver function test increases (including increases in GGT, GLDH, ALT, AST, or total bilirubin) were commonly reported, typically within 8 weeks following infusion; majority of cases were asymptomatic
                  • Cases observed resolved spontaneously or with systemic corticosteroids and resolved without clinical sequelae within 2 months; no cases of liver failure were reported
                  • Before administration, perform liver enzyme testing, then monitor liver function (clinical exam, GGT, and total bilirubin) weekly x 3 months following infusion
                  • Continue monitoring if clinically indicated, until results are unremarkable
                  • Systemic corticosteroid treatment recommended for patients before and after infusion; adjust corticosteroid regimen when indicated

                  Immune-mediated myositis

                  • Immune-mediated myositis observed ~1 month following infusion in patients with deletion mutations involving exon 8 and/or exon 9 in the DMD gene
                  • Symptoms of severe muscle weakness, including dysphagia, dyspnea, and hypophonia, were observed
                  • In a life-threatening case of immune-mediated myositis, symptoms resolved during hospitalization following additional immunomodulatory treatment; muscle strength gradually improved, but did not return to baseline level
                  • Immune reactions may be due to a T-cell based response from lack of self-tolerance to a specific region encoded by the transgene corresponding to exons 1-17 of the DMD gene
                  • Limited data are available regarding delandistrogene moxeparvovec treatment in patients with mutations in the DMD gene in exons 1-17 and/or exons 59-71; patients with deletions in these regions may be at risk for a severe immune-mediated myositis reaction
                  • Contraindicated in patients with any deletion in exon 8 and/or exon 9 in DMD gene due to increased risk for a severe immune-mediated myositis
                  • Advise caregivers to contact a physician immediately if child experiences any unexplained increased muscle pain, tenderness, or weakness, including dysphagia, dyspnea or hypophonia as these may be symptoms of myositis
                  • Consider additional immunomodulatory treatment (immunosuppressants [eg, calcineurin-inhibitor] in addition to corticosteroids) based on patient’s clinical presentation and medical history if these symptoms occur

                  Myocarditis

                  • Acute serious myocarditis and troponin-I elevations observed following infusion
                  • Monitor troponin-I before infusion and weekly for first month following infusion
                  • Continue monitoring if clinically indicated; more frequent monitoring may be warranted in the presence of cardiac symptoms (eg, chest pain, shortness of breath)
                  • Advise caregivers to contact a physician immediately if child experiences cardiac symptoms

                  Pre-existing immunity against AAVhr74

                  • In AAV-vector based gene therapies, preexisting anti-AAV antibodies may impede transgene expression at desired therapeutic levels
                  • Following treatment all subjects developed anti-AAVrh74 antibodies
                  • Perform baseline testing for presence of anti-AAVrh74 total binding antibodies before administration
                  • Not recommended in patients with elevated anti-AAVrh74 total binding antibody titers (≥1:400)

                  Drug interaction overview

                  • Vaccinations
                    • Complete vaccinations at least 4 weeks before initiating pretreatment corticosteroid regimen
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                  Pregnancy & Lactation

                  Pregnancy

                  Not intended for use in pregnant females

                  Lactation

                  Not intended for use in lactating females

                  Pregnancy Categories

                  A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                  B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                  C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                  D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                  X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                  NA: Information not available.

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                  Pharmacology

                  Mechanism of Action

                  DMD is caused by a mutation in DMD gene resulting in lack of functional dystrophin protein

                  Delandistrogene moxeparvovec carries a transgene encoding a micro-dystrophin protein consisting of selected domains of dystrophin expressed in normal muscle cells

                  Absorption

                  Peak plasma time: 5.3 hr (serum); 6.7 hr (saliva); 6.4 hr (urine); 13.5 days (feces)

                  Distribution

                  Undergoes distribution via systemic circulation and is distributed into target muscle tissues; eliminated in the urine and feces

                  Metabolism

                  Capsid proteins are broken down through proteasomal degradation following AAV entry into target cells

                  Elimination

                  Half-life (vector genome)

                  • Serum: ~12 hr
                  • Urine: 40 hr
                  • Feces: 55 hr
                  • Saliva: 60 hr

                  Clearance

                  • Majority of drug expected to be cleared from the serum by 1-week post-dose
                  • Median times to achieve complete elimination, defined as first below limit of detection (BLOD) sample followed by 2 consecutive BLOD samples, were 49.8 days, 123 days, and 162 days post dose for saliva, urine, and feces, respectively
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                  Administration

                  IV Preparation

                  General precautions

                  • Prepare using aseptic technique
                  • Verify required dose based on the patient’s body weight
                  • Confirm that kit contains sufficient number of vials to prepare infusion
                  • Visually inspect for particulate matter and discoloration before administration
                  • Delandistrogene moxeparvovec may contain white to off-white particles

                  Thaw before use

                  • Thaw in refrigerator: Vials stable for up to 14 days at 2-8ºC (36-46ºF) when stored in upright position
                  • Frozen vials will thaw in ~2 hr when placed at room temperature (up to 25ºC [77ºF]) when removed from original packaging
                  • Sealed thawed vials are stable up to 24 hr at room temperature (up to 25ºC [77ºF]) when stored in upright position

                  When thawed

                  • Inspect vials to ensure no ice crystals are present before preparation
                  • When thawed, swirl gently
                  • Do not shake
                  • Do not refreeze
                  • Do not place back in refrigerator

                  Visually inspect each vial

                  • Visually inspect; delandistrogene moxeparvovec is a clear, colorless liquid that may have some opalescence
                  • May contain white to off-white particles
                  • Do not use if suspension is cloudy or discolored

                  Draw up dose

                  • Remove plastic flip-off cap from vials and disinfect rubber stoppers with sterilizing agent (eg, alcohol wipes)
                  • Withdraw 10 mL from each vial provided in the customized kit (refer to prescribing information)
                  • Do not use filter needles during this process
                  • Multiple syringes will be required to withdraw required volume
                  • Remove air from syringes, and cap the syringes
                  • Maintain syringes at room temperature before and during administration

                  IV Administration

                  Administer as single-dose IV infusion through a peripheral venous catheter

                  Consider application of topical anesthetic to infusion site before administration of IV insertion

                  Recommend inserting a back-up catheter

                  Flush IV access line before delandistrogene moxeparvovec infusion at same infusion rate

                  Administer via IV infusion using a syringe infusion pump with an in-line 0.2-micron filter over a duration of ~1-2 hr, or longer at discretion of care team

                  Infusion

                  • Infuse at rate <10 mL/kg/hr
                  • Do NOT administer IV push
                  • Do NOT infuse in same IV access line with any other product
                  • Use within 4 hr after drawing into syringe; discard if infusion has not started within the 4-hr timeframe
                  • Flush IV access line with 0.9% NaCl when infusion completed
                  • Discard unused drug; dispose of needle and syringe

                  Monitoring post-infusion

                  • Assess liver function (clinical exam, GGT, and total bilirubin) weekly for the first 3 months; continue monitoring if clinically indicated, until results are unremarkable (normal clinical exam, GGT and total bilirubin levels returning to near baseline levels)
                  • Obtain platelet counts weekly for the first 2 weeks
                  • Continue monitoring if clinically indicated
                  • Measure troponin-I weekly for first month; continue monitoring if clinically indicated

                  Storage

                  Shipped and delivered at ≤ −60ºC (−76ºF)

                  May be refrigerated in upright position at 2-8ºC (36-46ºF) for up to 14 days

                  Do not refreeze

                  Do not shake

                  Do not place back in refrigerator once brought to room temperature

                  Follow local guidelines on handling of biological waste

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                  Patient Handout

                  A Patient Handout is not currently available for this monograph.
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                  Formulary

                  FormularyPatient Discounts

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                  The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                  Tier Description
                  1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                  2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                  3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                  4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  NC NOT COVERED – Drugs that are not covered by the plan.
                  Code Definition
                  PA Prior Authorization
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                  Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.