Version May 2024
Duchenne muscular dystrophy:
Note: Postpone therapy if any signs and/or symptoms of infection are present due to increased risk of systemic immune response; do not initiate therapy until infection is resolved. One day or 1 week (depending on baseline corticosteroid regimen) prior to infusion, begin oral corticosteroid regimen (see “Concomitant therapy”). Patient should be brought up to date on all age-appropriate vaccines based on current immunization schedules; vaccine should be administered ≥4 weeks prior to initiation of corticosteroid regimen. Evaluate baseline liver function, platelets, troponin-I, and anti-AAVrh74 total binding antibody titers; do not administer if anti-AAVrh74 total binding antibody titers are ≥1:400.
Children 4 to <6 years: IV infusion: 1.33 x 1014 vector genomes/kg as a single dose.
|
Weight range |
Dose volume |
|---|---|
|
10 to 10.4 kg |
100 mL |
|
10.5 to 11.4 kg |
110 mL |
|
11.5 to 12.4 kg |
120 mL |
|
12.5 to 13.4 kg |
130 mL |
|
13.5 to 14.4 kg |
140 mL |
|
14.5 to 15.4 kg |
150 mL |
|
15.5 to 16.4 kg |
160 mL |
|
16.5 to 17.4 kg |
170 mL |
|
17.5 to 18.4 kg |
180 mL |
|
18.5 to 19.4 kg |
190 mL |
|
19.5 to 20.4 kg |
200 mL |
|
20.5 to 21.4 kg |
210 mL |
|
21.5 to 22.4 kg |
220 mL |
|
22.5 to 23.4 kg |
230 mL |
|
23.5 to 24.4 kg |
240 mL |
|
24.5 to 25.4 kg |
250 mL |
|
25.5 to 26.4 kg |
260 mL |
|
26.5 to 27.4 kg |
270 mL |
|
27.5 to 28.4 kg |
280 mL |
|
28.5 to 29.4 kg |
290 mL |
|
29.5 to 30.4 kg |
300 mL |
|
30.5 to 31.4 kg |
310 mL |
|
31.5 to 32.4 kg |
320 mL |
|
32.5 to 33.4 kg |
330 mL |
|
33.5 to 34.4 kg |
340 mL |
|
34.5 to 35.4 kg |
350 mL |
|
35.5 to 36.4 kg |
360 mL |
|
36.5 to 37.4 kg |
370 mL |
|
37.5 to 38.4 kg |
380 mL |
|
38.5 to 39.4 kg |
390 mL |
|
39.5 to 40.4 kg |
400 mL |
|
40.5 to 41.4 kg |
410 mL |
|
41.5 to 42.4 kg |
420 mL |
|
42.5 to 43.4 kg |
430 mL |
|
43.5 to 44.4 kg |
440 mL |
|
44.5 to 45.4 kg |
450 mL |
|
45.5 to 46.4 kg |
460 mL |
|
46.5 to 47.4 kg |
470 mL |
|
47.5 to 48.4 kg |
480 mL |
|
48.5 to 49.4 kg |
490 mL |
|
49.5 to 50.4 kg |
500 mL |
|
50.5 to 51.4 kg |
510 mL |
|
51.5 to 52.4 kg |
520 mL |
|
52.5 to 53.4 kg |
530 mL |
|
53.5 to 54.4 kg |
540 mL |
|
54.5 to 55.4 kg |
550 mL |
|
55.5 to 56.4 kg |
560 mL |
|
56.5 to 57.4 kg |
570 mL |
|
57.5 to 58.4 kg |
580 mL |
|
58.5 to 59.4 kg |
590 mL |
|
59.5 to 60.4 kg |
600 mL |
|
60.5 to 61.4 kg |
610 mL |
|
61.5 to 62.4 kg |
620 mL |
|
62.5 to 63.4 kg |
630 mL |
|
63.5 to 64.4 kg |
640 mL |
|
64.5 to 65.4 kg |
650 mL |
|
65.5 to 66.4 kg |
660 mL |
|
66.5 to 67.4 kg |
670 mL |
|
67.5 to 68.4 kg |
680 mL |
|
68.5 to 69.4 kg |
690 mL |
|
≥69.5 kg |
700 mL |
Concomitant therapy: Prior to delandistrogene moxeparvovec infusion, an oral corticosteroid regimen should be administered to reduce the risk of an immune response and continued for ≥60 days unless early tapering is indicated. Corticosteroid dose for pre- and post- delandistrogene infusion and taper are determined by patient's previous baseline corticosteroid regimen (see tables; dose modification required for abnormal liver function).
|
Baseline corticosteroid dosing |
Corticosteroid regimena |
Recommended maximum total daily dose |
Corticosteroid taper |
|---|---|---|---|
|
a Deflazacort is not recommended for use as the corticosteroid for this purpose. | |||
|
Daily or intermittent dosing |
Start 1 day prior to infusion: Prednisone 1 mg/kg/day (or equivalent) and continue baseline dose. |
60 mg/day (prednisone equivalent) |
Taper over 2 weeks or longer if clinically indicated. |
|
High dose for 2 days/week |
Start 1 day prior to infusion: Prednisone 1 mg/kg/day (or equivalent) on days without high-dose corticosteroid treatment and continue baseline dose. |
60 mg/day (prednisone equivalent) |
Taper over 2 weeks or longer if clinically indicated. |
|
Not on corticosteroids |
Start 1 week prior to infusion: 1.5 mg/kg/day. |
60 mg/day (prednisone equivalent) |
Taper over 4 weeks or longer if clinically indicated |
Hepatic impairment following infusion (GGT ≥150 U/L and/or other clinically significant liver function abnormalities [eg, total bilirubin >2 x ULN]): Modify corticosteroid dose (see table).
|
Baseline corticosteroid dosing |
Modified corticosteroid dosea |
Recommended maximum total daily dose |
|---|---|---|
|
a Deflazacort is not recommended for use as the corticosteroid for this purpose. | ||
|
Daily or intermittent dosing |
Increase to prednisone 2 mg/kg/day (or equivalent) and continue baseline dose. |
120 mg/day (prednisone equivalent) |
|
High dose for 2 days/week |
Increase to prednisone 2 mg/kg/day (or equivalent) taken on days without high-dose corticosteroid treatment and continue baseline dose. |
120 mg/day (prednisone equivalent) |
|
Not on corticosteroids |
Increase to prednisone 2.5 mg/kg/day (or equivalent). |
120 mg/day (prednisone equivalent) |
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Postpone administration in patients with acute liver disease until resolved or controlled. Patients with preexisting hepatic impairment or chronic hepatic viral infection may be at increased risk for hepatotoxicity; assess risk vs benefit. Acute liver injury may occur after therapy and may require adjustment of concomitant corticosteroid dose (see "Dosing: Pediatric"). Monitor liver function closely (clinical exams, GGT, and total bilirubin).
Acute serious liver injury, including increased liver enzymes and increased serum bilirubin, have been observed with delandistrogene moxeparvovec. Most cases resolved spontaneously or with corticosteroids and resolved within 2 months, although one case required hospitalization (Ref). There have been no cases of liver failure reported (Ref).
Mechanism: Dose-related; related to pharmacologic action. Associated with adaptive immune response on the liver secondary to viral capsid degradation and presentation by hepatocytes (Ref).
Onset: Delayed; liver function test elevation has been reported 7 to 8 weeks post infusion (Ref).
Risk factors:
• Preexisting liver impairment, chronic hepatic condition, or acute liver disease
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for children.
>10%:
Gastrointestinal: Nausea (35%), vomiting (65%)
Hepatic: Increased liver enzymes (25%; including increased gamma-glutamyl transferase, increased glutamate dehydrogenase, increased serum alanine aminotransferase, increased serum aspartate aminotransferase, increased serum bilirubin) (table 1)
|
Drug (Delandistrogene Moxeparvovec) |
Placebo |
Population |
Number of Patients (Delandistrogene Moxeparvovec) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
25% |
0% |
Children |
20 |
21 |
Immunologic: Antibody development
Miscellaneous: Fever (20%)
Frequency not defined:
Cardiovascular: Myocarditis, troponin increased in blood specimen
Hepatic: Hepatic injury
Any deletion in exon 8 and/or exon 9 in the Duchenne muscular dystrophy gene.
Concerns related to adverse effects:
• Myositis: Immune-mediated myositis has been observed in patients with deletion mutations involving exon 8 and/or exon 9 in the Duchenne muscular dystrophy gene ~1 month after initial infusion. Consult physician immediately if unexplained muscle pain, tenderness, or weakness, including dysphagia, dyspnea, or hypophonia, occurs; immunomodulatory treatment (eg, immunosuppressants [eg, calcineurin inhibitor]) may be considered if these symptoms occur.
Elevidys is provided in a customized kit containing ten to seventy 10 mL single-dose vials, with each kit constituting a dosage unit based on the patient’s body weight.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Intravenous [preservative free]:
Elevidys: Delandistrogene moxeparvovec-rokl 1.33 × 1013 vector genomes/mL
No
Kit (Elevidys 10.0-10.4 kg Intravenous)
10 x 10 mL (per each): $0.00
Kit (Elevidys 10.5-11.4 kg Intravenous)
11 x 10 mL (per each): $0.00
Kit (Elevidys 11.5-12.4 kg Intravenous)
12 x 10 mL (per each): $0.00
Kit (Elevidys 12.5-13.4 kg Intravenous)
13 x 10 mL (per each): $0.00
Kit (Elevidys 13.5-14.4 kg Intravenous)
14 x 10 mL (per each): $0.00
Kit (Elevidys 14.5-15.4 kg Intravenous)
15 x 10 mL (per each): $0.00
Kit (Elevidys 15.5-16.4 kg Intravenous)
16 x 10 mL (per each): $0.00
Kit (Elevidys 16.5-17.4 kg Intravenous)
17 x 10 mL (per each): $0.00
Kit (Elevidys 17.5-18.4 kg Intravenous)
18 x 10 mL (per each): $0.00
Kit (Elevidys 18.5-19.4 kg Intravenous)
19 x 10 mL (per each): $0.00
Kit (Elevidys 19.5-20.4 kg Intravenous)
20 x 10 mL (per each): $0.00
Kit (Elevidys 20.5-21.4 kg Intravenous)
21 x 10 mL (per each): $0.00
Kit (Elevidys 21.5-22.4 kg Intravenous)
22 x 10 mL (per each): $0.00
Kit (Elevidys 22.5-23.4 kg Intravenous)
23 x 10 mL (per each): $0.00
Kit (Elevidys 23.5-24.4 kg Intravenous)
24 x 10 mL (per each): $0.00
Kit (Elevidys 24.5-25.4 kg Intravenous)
25 x 10 mL (per each): $0.00
Kit (Elevidys 25.5-26.4 kg Intravenous)
26 x 10 mL (per each): $0.00
Kit (Elevidys 26.5-27.4 kg Intravenous)
27 x 10 mL (per each): $0.00
Kit (Elevidys 27.5-28.4 kg Intravenous)
28 x 10 mL (per each): $0.00
Kit (Elevidys 28.5-29.4 kg Intravenous)
29 x 10 mL (per each): $0.00
Kit (Elevidys 29.5-30.4 kg Intravenous)
30 x 10 mL (per each): $0.00
Kit (Elevidys 30.5-31.4 kg Intravenous)
31 x 10 mL (per each): $0.00
Kit (Elevidys 31.5-32.4 kg Intravenous)
32 x 10 mL (per each): $0.00
Kit (Elevidys 32.5-33.4 kg Intravenous)
33 x 10 mL (per each): $0.00
Kit (Elevidys 33.5-34.4 kg Intravenous)
34 x 10 mL (per each): $0.00
Kit (Elevidys 50.5-51.4 kg Intravenous)
51 x 10 mL (per each): $0.00
Kit (Elevidys 59.5-60.4 kg Intravenous)
60 x 10 mL (per each): $0.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Parenteral: IV: For IV infusion only; do not administer as IV push. Administer peripherally through PVC (non-DEHP), polyurethane IV infusion tubing with a 0.2 micron polyether sulfone in-line filter via a syringe pump over at least 1 to 2 hours; infuse at a rate of <10 mL/kg/hour. Flush with NS before and after administration.
Product is shipped and delivered at ≤−60°C (≤−76°F). Upon receipt, store upright at 2°C to 8°C (36°F to 46°F) for ≤14 days. Do not refreeze; do not return to refrigerator once brought to room temperature. Follow local guidelines on handling of biological waste.
Treatment of Duchenne muscular dystrophy (DMD) in ambulatory patients with a confirmed mutation in the DMD gene (FDA approved in ages 4 to <6 years).
Note: FDA approval for this indication is through an accelerated process; continued approval is dependent on verification of clinical benefit in further trials.
None known.
There are no known significant interactions.
Delandistrogene moxeparvovec is not intended for use in persons who are pregnant.
Baseline: Liver function, platelets, troponin-I, anti-AAVrh74 antibody titers, signs and symptoms of infection.
Following treatment: Liver function (clinical exam, GGT, and total bilirubin) weekly for 3 months; continue monitoring if clinically indicated until normal clinical exam and GGT and total bilirubin return to near baseline levels. Platelets weekly for 2 weeks or longer if clinically indicated. Troponin-I weekly for 1 month or longer if clinically indicated. Signs and symptoms of infection (eg, coughing, wheezing, sneezing, runny nose, sore throat, fever), myositis (unexplained increased muscle pain, tenderness, or weakness, including difficulty swallowing, difficulty breathing, or difficulty speaking) and myocarditis (eg, chest pain, shortness of breath).
Delandistrogene moxeparvovec is a nonreplicating, recombinant adeno-associated virus serotype rh74 vector-based gene therapy that delivers a normal copy of the gene encoding a micro-dystrophin protein expressed in normal muscle cells.
Distribution: Distributes into target muscle tissue groups; vector DNA was detected in all major organs, with the highest amount detected in the liver.
Half-life elimination: Serum: 12 hours; saliva: 60 hours; urine: 40 hours; feces: 55 hours.
Excretion: Urine; feces.
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