ELEVIDYS Suspension for solution for infusion Ref.[107289] Active ingredients: Delandistrogene moxeparvovec

For single-dose intravenous infusion only.

2.1 Patient Selection

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

2.2 Dose

The recommended dose of ELEVIDYS is 1.33 × 10¹⁴ vector genomes per kilogram (vg/kg) of body weight (or 10 mL/kg body weight). For the number of vials required, refer to Table 7 [see How Supplied/Storage and Handling (16.1)].

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

Prior to ELEVIDYS infusion:

• Due to the increased risk of serious systemic immune response, postpone ELEVIDYS in patients with infections until the infection has resolved. Clinical signs or symptoms of infection should not be evident at the time of ELEVIDYS administration [see Patient Counseling Information (17)].
• Assess liver function [see Dosage and Administration (2.4), Warnings and Precautions (5.1), Use in Specific Populations (8.6)].
• Obtain platelet count and troponin-I levels [see Dosage and Administration (2.4), Warnings and Precautions (5.3)].
• Measure baseline anti-AAVrh74 antibody titers using a Total Binding Antibody enzyme-linked immunosorbent assay (ELISA) [see Dosage and Administration (2), Clinical Pharmacology (12.6)].

ELEVIDYS administration is not recommended in patients with elevated anti-AAVrh74 total binding antibody titers (≥1:400). Re-administration of ELEVIDYS is not recommended [see Warnings and Precautions (5.4), Clinical Pharmacology (12.6)].

Immune responses to the AAVrh74 vector can occur after administration of ELEVIDYS [see Clinical Pharmacology (12.6)]. To reduce the risk associated with an immune response, corticosteroids should be administered starting 1 day prior to ELEVIDYS infusion. Initiate a corticosteroid regimen following the appropriate schedule (see Table 1). This regimen is recommended for a minimum of 60 days after the infusion, unless earlier tapering is clinically indicated. Table 2 includes the recommended corticosteroid regimen dose modification for patients with liver function abnormalities following ELEVIDYS infusion. If acute serious liver injury is suspected, a consultation with a specialist is recommended.

For patients previously taking corticosteroids at baseline, taper off the additional peri-ELEVIDYS corticosteroids (back to baseline corticosteroid dose) over 2 weeks, or longer as needed. For patients not previously taking corticosteroids at baseline, taper the added peri-ELEVIDYS corticosteroids off (back to no corticosteroids) over 4 weeks, or longer, as needed, and the corticosteroids should not be stopped abruptly.

Table 1. Recommended pre- and post-infusion corticosteroid dosing:

^a Patient continues to receive this dose
^b Deflazacort is not recommended for use as a peri-ELEVIDYS infusion corticosteroid

Table 2. Recommended corticosteroid regimen dose modification for liver function abnormalities following ELEVIDYS infusion^a:

^a GGT ≥150 U/L and/or other clinically significant liver function abnormalities (e.g., 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.
^b Deflazacort is not recommended for use as a peri-ELEVIDYS infusion corticosteroid

2.3 Preparation

General precautions:

• Prepare ELEVIDYS using aseptic technique.
• Verify the required dose of ELEVIDYS based on the patient’s body weight.
• Confirm that the kit contains sufficient number of vials to prepare the ELEVIDYS infusion for the patient.
• Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever suspension and container permit. ELEVIDYS may contain white to off-white particles.

Recommended supplies and materials:

• 60 mL siliconized polypropylene syringes
• 21-gauge or smaller stainless steel needles

Preparing ELEVIDYS infusion:

• Thaw ELEVIDYS before use.
  • When thawed in the refrigerator, ELEVIDYS vials are stable for up to 14 days in the refrigerator (2°C to 8°C [36ºF to 46ºF]) when stored in the upright position.
  • Frozen ELEVIDYS vials will thaw in approximately 2 hours when placed at room temperature (up to 25°C [77ºF]) when removed from original packaging.
• Inspect vials to ensure no ice crystals are present prior to preparation.
• When thawed, swirl gently.
  • Do not shake.
  • Do not refreeze.
  • Do not place back in the refrigerator.
• Visually inspect each vial of ELEVIDYS. ELEVIDYS is a clear, colorless liquid that may have some opalescence. ELEVIDYS may contain white to off-white particles.
  • Do not use if the suspension in the vials is cloudy or discolored.
• Remove the plastic flip-off cap from the vials and disinfect the rubber stopper with a sterilizing agent (e.g., alcohol wipes).
• Withdraw 10 mL of ELEVIDYS from each vial provided in the customized ELEVIDYS kit (refer to Table 7).
  • Do not use filter needles during preparation of ELEVIDYS.
  • Multiple syringes will be required to withdraw the required volume.
  • Remove air from the syringes and cap the syringes.
• Maintain syringes at room temperature prior to and during administration.
  • Sealed ELEVIDYS thawed vials are stable up to 24 hours at room temperature (up to 25°C [77ºF]) when stored in upright position.

2.4 Administration

Recommended supplies and materials:

• Syringe infusion pump
• 0.2-micron PES* in-line filter
• PVC* (non-DEHP*), polyurethane IV infusion tubing and catheter

^* PVC = Polyvinyl chloride, DEHP = Di(2-ethylhexyl) phthalate, PES = Polyether sulfone

Administer ELEVIDYS as a single-dose intravenous infusion through a peripheral venous catheter:

Consider application of a topical anesthetic to the infusion site prior to administration of IV insertion.

Recommend inserting a back-up catheter.

• Flush the intravenous access line prior to the ELEVIDYS infusion at the same infusion rate.
• Administer ELEVIDYS via intravenous infusion using a syringe infusion pump with an in-line 0.2-micron filter at a duration of approximately 1 to 2 hours, or longer at care team discretion, through a peripheral limb vein.
• Infuse at a rate of less than 10 mL/kg/hour.
  • Do not administer ELEVIDYS as an intravenous push.
  • Do not infuse ELEVIDYS in the same intravenous access line with any other product.
  • Use ELEVIDYS within 6 hours after drawing into syringe. Discard the ELEVIDYS-containing syringe(s) if infusion of the drug has not started within the 6 hour timeframe.
• Flush the intravenous access line with 0.9% Sodium Chloride Injection after the ELEVIDYS infusion.
  • Discard unused ELEVIDYS [see How Supplied/Storage and Handling (16.2)].
  • Dispose of the needle and syringe [see How Supplied/Storage and Handling (16.2)].

Monitoring Post-ELEVIDYS Administration

• 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 return to near baseline levels) [see Warning and Precautions (5.1), Specific Populations (8.6)].
• Obtain platelet counts weekly for the first two weeks [see Adverse Reactions (6.1)]. Continue monitoring if clinically indicated.
• Measure troponin-I weekly for the first month [see Warning and Precautions (5.3)]. Continue monitoring if clinically indicated.

• ELEVIDYS is shipped and delivered at ≤ −60ºC [−76ºF].
• ELEVIDYS can be refrigerated for up to 14 days when stored at 2°C to 8°C (36ºF to 46ºF) in the upright position.
• Do not refreeze.
• Do not shake.
• Do not place back in the refrigerator once brought to room temperature.
• Follow local guidelines on handling of biological waste.