Active Ingredient: Delandistrogene moxeparvovec
Delandistrogene moxeparvovec is 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.
This indication is approved under accelerated approval based on expression of delandistrogene moxeparvovec micro-dystrophin observed in patients treated with delandistrogene moxeparvovec. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
For this indication, competent medicine agencies globally authorize below treatments:
For:
In case that patient age in years is ≥ 4 and patient age in years is ≤ 5, intravenous, 133,000,000,000,000 copies delandistrogene moxeparvovec per kilogram of body weight, one dose.
The recommended dose is 1.33 × 1014 vector genomes per kilogram (vg/kg) of body weight (or 10 mL/kg body weight).
Prior to delandistrogene moxeparvovec infusion:
Delandistrogene moxeparvovec administration is not recommended in patients with elevated anti-AAVrh74 total binding antibody titers (≥1:400). Re-administration of delandistrogene moxeparvovec is not recommended.
Immune responses to the AAVrh74 vector can occur after administration of delandistrogene moxeparvovec. To reduce the risk associated with an immune response, corticosteroids should be administered starting 1 day prior to delandistrogene moxeparvovec 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 delandistrogene moxeparvovec 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-delandistrogene moxeparvovec 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-delandistrogene moxeparvovec 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:
| Baseline corticosteroid dosinga | Peri-delandistrogene moxeparvovec infusion corticosteroid dose (prednisone equivalent)b | Recommended maximum total daily dose (prednisone equivalent)b |
|---|---|---|
| Daily or intermittent dose | Start 1 day prior to infusion: 1 mg/kg/day (and continue baseline dose) | 60 mg/day |
| High dose for 2 days per week | Start 1 day prior to infusion: 1 mg/kg/day taken on days without high-dose corticosteroid treatment (and continue baseline dose) | 60 mg/day |
| Not on corticosteroids | Start 1 week prior to infusion: 1.5 mg/kg/day | 60 mg/day |
a Patient continues to receive this dose.
b Deflazacort is not recommended for use as a peri-delandistrogene moxeparvovec infusion corticosteroid.
Table 2. Recommended corticosteroid regimen dose modification for liver function abnormalities following delandistrogene moxeparvovec infusiona:
| Peri-delandistrogene moxeparvovec infusion corticosteroid dosing | Modified corticosteroid dose following delandistrogene moxeparvovec infusion (prednisone equivalent)b | Recommended maximum total daily dose (prednisone equivalent)b |
|---|---|---|
| Baseline + 1 mg/kg/day | Increase to 2 mg/kg/day (and continue baseline dose) | 120 mg/day |
| Baseline + 1 mg/kg/day taken on days without high- dose corticosteroid treatment | Increase to 2 mg/kg/day taken on days without high-dose corticosteroid treatment (and continue baseline dose) | 120 mg/day |
| 1.5 mg/kg/day | Increase from 1.5 mg/kg/day to 2.5 mg/kg/day | 120 mg/day |
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-delandistrogene moxeparvovec infusion corticosteroid.
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