1. Indications and Usage for Elevidys
ELEVIDYS 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 ELEVIDYS micro-dystrophin observed in patients treated with ELEVIDYS [see Clinical Pharmacology (12), Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
2. Elevidys Dosage and Administration
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
|
|
|
|
| Baseline corticosteroid dosinga | Peri-ELEVIDYS 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
|
Table 2: Recommended corticosteroid regimen dose modification for liver function abnormalities following ELEVIDYS infusiona
|
|
|
|
| Peri-ELEVIDYS infusion corticosteroid dosing | Modified corticosteroid dose following ELEVIDYS 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
|
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 [36º F to 46º F]) 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.
3. Dosage Forms and Strengths
ELEVIDYS is a preservative-free, sterile, clear, colorless liquid that may have some opalescence and may contain white to off-white particles.
ELEVIDYS is a suspension for intravenous infusion with a nominal concentration of 1.33 × 1013 vg/mL.
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 [see How Supplied/Storage and Handling (16.1)].
The intravenous dosage is determined by patient body weight, with a recommended dose of 1.33 × 1014 vector genomes (vg)/kg.
4. Contraindications
ELEVIDYS is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene [see Warnings and Precautions (5.2)].
5. Warnings and Precautions
5.1 Acute Serious Liver Injury
Acute serious liver injury has been observed with ELEVIDYS. Administration of ELEVIDYS may result in elevations of liver enzymes (e.g., GGT, ALT) and total bilirubin, typically seen within 8 weeks.
Patients with preexisting liver impairment, chronic hepatic condition or acute liver disease (e.g., acute hepatic viral infection) may be at higher risk of acute serious liver injury. Postpone ELEVIDYS 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 with ELEVIDYS [see Specific Populations (8.6)].
In clinical studies, liver function test increased (including increases in GGT, GLDH, ALT, AST, or total bilirubin) was commonly reported typically within 8 weeks following ELEVIDYS infusion, with the majority of cases being asymptomatic [see Adverse Reactions (6.1)]. Cases resolved spontaneously or with systemic corticosteroids and resolved without clinical sequelae within 2 months. No cases of liver failure were reported.
Prior to ELEVIDYS administration, perform liver enzyme test [see Dosage and Administration (2.2)]. Monitor liver function (clinical exam, GGT, and total bilirubin) weekly for the first 3 months following ELEVIDYS infusion. Continue monitoring if clinically indicated, until results are unremarkable (normal clinical exam, GGT and total bilirubin levels return to near baseline levels) [see Dosage and Administration (2.4)].
Systemic corticosteroid treatment is recommended for patients before and after ELEVIDYS infusion [see Dosage and Administration (2.2)]. Adjust corticosteroid regimen when indicated [see Dosage and Administration (2.2)]. If acute serious liver injury is suspected, a consultation with a specialist is recommended.
5.2 Immune-mediated Myositis
In clinical trials, immune-mediated myositis has been observed approximately 1 month following ELEVIDYS 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. These 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 for ELEVIDYS treatment in patients with mutations in the DMD gene in exons 1 to 17 and/or exons 59 to 71 [see Clinical Studies (14)]. Patients with deletions in these regions may be at risk for a severe immune-mediated myositis reaction. ELEVIDYS is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene due to the increased risk for a severe immune-mediated myositis reaction [see Contraindications (4)].
Advise patients to contact a physician immediately if they experience 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 [e.g., calcineurin-inhibitor] in addition to corticosteroids) based on patient's clinical presentation and medical history if these symptoms occur.
5.3 Myocarditis
Acute serious myocarditis and troponin-I elevations have been observed following ELEVIDYS infusion in clinical trials.
Monitor troponin-I before ELEVIDYS infusion and weekly for the first month following infusion [see Dosage and Administration (2.4)]. Continue monitoring if clinically indicated. More frequent monitoring may be warranted in the presence of cardiac symptoms, such as chest pain or shortness of breath.
Advise patients to contact a physician immediately if they experience cardiac symptoms.
5.4 Pre-existing Immunity against AAVrh74
In AAV-vector based gene therapies, preexisting anti-AAV antibodies may impede transgene expression at desired therapeutic levels. Following treatment with ELEVIDYS all subjects developed anti-AAVrh74 antibodies. Perform baseline testing for the presence of anti-AAVrh74 total binding antibodies prior to ELEVIDYS administration [see Dosage and Administration (2.1)].
ELEVIDYS administration is not recommended in patients with elevated anti-AAVrh74 total binding antibody titers (≥1:400).
6. Adverse Reactions/Side Effects
The most common adverse reactions (incidence ≥ 5%) reported in clinical studies were vomiting, nausea, liver function test increased, pyrexia, and thrombocytopenia.
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Acute serious liver injury [see Warnings and Precautions (5.1)]
- Immune-mediated myositis [see Warnings and Precautions (5.2)]
- Myocarditis [see Warnings and Precautions (5.3)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety data described in this section reflect exposure to a one-time intravenous infusion of ELEVIDYS in 85 male subjects with a confirmed mutation of the DMD gene in three on-going clinical studies, including two open-label studies and one study that included a double-blind, placebo-controlled period. Prior to ELEVIDYS infusion, patients in the ELEVIDYS treatment group had a mean age of 7.08 years (range: 3 to 20) and mean weight of 25.91 kg (range: 12.5 to 80.1). 73 subjects received the recommended dose of 1.33 × 1014 vg/kg, and 12 received a lower dose. Table 3 below presents adverse reactions from these three clinical studies.
The most common adverse reactions (incidence ≥5%) across all studies are summarized in Table 3.
Adverse reactions were typically seen within the first 2 weeks (nausea, vomiting, thrombocytopenia, pyrexia), or within the first 2 months (immune-mediated myositis, liver function test increased). Vomiting may occur as early as on the day of the infusion.
Table 3. Adverse reactions (Incidence ≥5%) following treatment with ELEVIDYS in Clinical Studies
|
|
|
|
| Adverse reactions | ELEVIDYS
(N=85) % |
| Vomiting
| 61
|
| Nausea
| 40
|
| Liver function test increaseda | 37
|
| Pyrexia
| 24
|
| Thrombocytopeniab | 12
|
In the double-blind, placebo-controlled trial (Study 1 Part 1), subjects 4 to 7 years of age (N=41) received either ELEVIDYS (N=20) at the recommended dose of 1.33 × 1014 vg/kg (n=8) or lower dose (n=12) or received placebo (N=21). Table 4 below presents the most frequent adverse reactions from Study 1 Part 1.
Table 4. Adverse reactions occurring in ELEVIDYS-treated subjects and at least 10% more frequently than in placebo in Study 1, Part 1
|
|
| Adverse reactions | ELEVIDYS
(N=20) % | Placebo
(N=21) % |
| Vomiting
| 65
| 33
|
| Nausea
| 35
| 10
|
| Liver function test increaseda | 25
| 0
|
| Pyrexia
| 20
| 5
|
7. Drug Interactions
Prior to initiating the corticosteroid regimen required before ELEVIDYS administration, consider the patient's vaccination status. Patients should, if possible, be brought up-to-date with all immunizations in agreement with current immunization guidelines. Vaccinations should be completed at least 4 weeks prior to initiation of the corticosteroid regimen.
8. Use In Specific Populations
8.1 Pregnancy
Risk Summary
ELEVIDYS is not intended for use in pregnant women.
In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
8.2 Lactation
Risk Summary
There is no information available on the presence of ELEVIDYS in human milk, the effects on the breastfed infant, or the effects on milk production.
8.4 Pediatric Use
ELEVIDYS is indicated for the treatment of ambulatory pediatric patients 4 through 5 years of age with Duchenne muscular dystrophy with a confirmed mutation in the DMD gene. This indication is based on expression of ELEVIDYS micro-dystrophin protein in skeletal muscle observed in DMD patients treated with ELEVIDYS. The effectiveness and safety of ELEVIDYS has not been established in pediatric patients younger than 3 years of age. The effectiveness of ELEVIDYS has not been established in pediatric patients 3 years of age and in pediatric patients 6 years of age and older [see Clinical Pharmacology (12.2), Clinical Studies (14)].
8.5 Geriatric Use
The safety and efficacy of ELEVIDYS in geriatric patients with DMD have not been studied.
8.6 Hepatic Impairment
The safety and efficacy of ELEVIDYS in patients with hepatic impairment or elevated GGT have not been studied.
Postpone ELEVIDYS administration in patients with acute liver disease until resolved or controlled. ELEVIDYS therapy should be carefully considered in patients with preexisting liver impairment or chronic hepatic viral infection. These patients may be at increased risk of acute serious liver injury [see Warnings and Precautions (5.1)].
In clinical trials, liver function test increase was commonly reported in subjects following ELEVIDYS infusion [see Warnings and Precautions (5.1), Adverse Reactions (6.1)].
11. Elevidys Description
ELEVIDYS (delandistrogene moxeparvovec-rokl) is a recombinant gene therapy designed to deliver the gene encoding the ELEVIDYS micro-dystrophin protein. ELEVIDYS is a non-replicating, recombinant, adeno-associated virus serotype rh74 (AAVrh74) based vector containing the ELEVIDYS micro-dystrophin transgene under the control of the MHCK7 promoter. The genome within the ELEVIDYS AAVrh74 vector contains no viral genes and consequently is incapable of replication or reversion to a replicating form. The micro-dystrophin protein expressed by ELEVIDYS is a shortened version (138 kDa, compared to 427 kDa size of dystrophin expressed in normal muscle cells) that contains selected domains of dystrophin expressed in normal muscle cells.
ELEVIDYS is a preservative-free, sterile, clear, colorless liquid that may have some opalescence and may contain white to off-white particles. ELEVIDYS is a suspension for intravenous infusion with a nominal concentration of 1.33 ×1013 vg/mL and supplied in a single-dose 10 mL vial. Each vial contains an extractable volume of 10 mL and the following excipients: 200mM sodium chloride, 13 mM tromethamine HCl, 7 mM tromethamine, 1mM magnesium chloride, 0.001% poloxamer 188.
12. Elevidys - Clinical Pharmacology
12.1 Mechanism of Action
ELEVIDYS is the recombinant gene therapy product that is comprised of a non-replicating, recombinant, adeno-associated virus (AAV) serotype rh74 (AAVrh74) capsid and a ssDNA expression cassette flanked by inverted terminal repeats (ITRs) derived from AAV2. The cassette contains: 1) an MHCK7 gene regulatory component comprising a creatine kinase 7 promoter and an α-myosin heavy chain enhancer, and 2) the DNA transgene encoding the engineered ELEVIDYS micro-dystrophin protein.
Vector/Capsid: Clinical and nonclinical studies have demonstrated AAVrh74 serotype transduction in skeletal muscle cells. Additionally, in nonclinical studies, AAVrh74 serotype transduction has been demonstrated in cardiac and diaphragm muscle cells.
Promoter: The MHCK7 promoter/enhancer drives transgene expression and has been shown in animal models to drive transgenic ELEVIDYS micro-dystrophin protein expression predominantly in skeletal muscle (including diaphragm) and cardiac muscle. In clinical studies, muscle biopsy analyses have confirmed ELEVIDYS micro-dystrophin expression in skeletal muscle.
Transgene: DMD is caused by a mutation in the DMD gene resulting in lack of functional dystrophin protein. ELEVIDYS carries a transgene encoding a micro-dystrophin protein consisting of selected domains of dystrophin expressed in normal muscle cells.
ELEVIDYS micro-dystrophin has been demonstrated to localize to the sarcolemma.
12.2 Pharmacodynamics
In 61 subjects who received ELEVIDYS in clinical studies, ELEVIDYS micro-dystrophin protein expression from muscle biopsies (gastrocnemius) was quantified by western blot and localized by immunofluorescence staining (fiber intensity and percentage ELEVIDYS micro-dystrophin).
ELEVIDYS micro-dystrophin expression (expressed as change from baseline) as measured by western blot was the primary objective of Study 1 and Study 2. Muscle biopsies were obtained at baseline prior to ELEVIDYS infusion and at Week 12 after ELEVIDYS infusion in all subjects. The absolute quantity of ELEVIDYS micro-dystrophin was measured by western blot assay, adjusted by muscle content and expressed as a percent of control (levels of wild-type dystrophin in subjects without DMD or Becker muscular dystrophy) in muscle biopsy samples. Results of subjects receiving 1.33 × 1014 vg/kg ELEVIDYS are presented in Table 5.
Table 5: ELEVIDYS Micro-Dystrophin Expression in Studies 1 and 2 (Western Blot Assay)abcd
| Western blot (% of ELEVIDYS micro-dystrophin compared to control) | Study 1
(Week 12)
Part 1
(n = 6) | Study 1
(Week 12)
Part 2
(n=21) | Study 2
(Week 12) Cohort 1
(n = 20) |
|
|
|
|
|
|
|
|
| Mean change from baseline (SD)
| 43.4
(48.6)
| 40.7
(32.3)
| 54.2
(42.6)
|
| Median change from baseline (Min, Max)
| 24.3
(1.6, 116.3)
| 40.8
(0.0, 92.0)
| 50.6
(4.8, 153.9)
|
For subjects aged 4 through 5 years who received 1.33 × 1014 vg/kg of ELEVIDYS, the mean (SD) ELEVIDYS micro-dystrophin expression levels (change from baseline) at Week 12 following ELEVIDYS infusion were 95.7% (N=3, SD: 17.9%) in Study 1 Parts 1 and 2 and 51.7% (N=11, SD: 41.0%) in Study 2 Cohort 1.
Assessment of ELEVIDYS micro-dystrophin levels can be meaningfully influenced by differences in sample processing, analytical technique, reference materials, and quantitation methodologies. Therefore, valid comparisons of ELEVIDYS micro-dystrophin measurements obtained from different assays cannot be made.
12.3 Pharmacokinetics
Vector Distribution and Vector Shedding
Nonclinical Data
Biodistribution of ELEVIDYS was evaluated in tissue samples collected from healthy mice and Dmdmdx mice following intravenous administration in toxicology studies. At 12 weeks following ELEVIDYS administration at dose levels of 1.33 ×1014 to 4.02 ×1014 vg/kg, vector DNA was detected in all major organs with the highest quantities detected in the liver, followed by lower levels in the heart, adrenal glands, skeletal muscle, and aorta. ELEVIDYS was also detected at low levels in the spinal cord, sciatic nerve and gonads (testis). Protein expression of ELEVIDYS micro-dystrophin was highest in cardiac tissue, exceeding physiologic dystrophin expression levels in healthy mice, with lower levels in the skeletal muscle and diaphragm. In some studies, micro-dystrophin was also detected at low levels in the liver.
Clinical Data
Following IV administration, ELEVIDYS vector genome undergoes distribution via systemic circulation and distributes into target muscle tissues followed by elimination in the urine and feces. ELEVIDYS biodistribution and tissue transduction are detected in the target muscle tissue groups and quantified in the gastrocnemius or biceps femoris biopsies obtained from patients with mutations in the DMD gene. Evaluation of ELEVIDYS vector genome exposure in clinical muscle biopsies at Week 12 post-dose expressed as copies per nucleus revealed ELEVIDYS drug distribution and transduction with a mean change from baseline of 2.91 and 3.44 copies per nucleus at the recommended dose of 1.33 × 1014 vg/kg for Study 1 and Study 2 Cohort 1, respectively.
In Study 2 Cohort 1, the biodistribution and vector shedding of ELEVIDYS in the serum and excreta were quantified, respectively. The mean maximum concentration (Cmax) in the serum was 0.0049 × 1013 copies/mL and 4.11 × 105 copies/mL in the urine, 4.72 × 107 copies/mL in the saliva, and 2.32 × 107 copies/μg in the feces. The median time to achieve maximum concentration (Tmax) was 5.3 hours post-dose in the serum, followed by 6.7 hours, 6.4 hours and 13.5 days post-dose in the saliva, urine, and feces, respectively. The median time to achieve first below limit of quantification (BLOQ) sample followed by 2 consecutive BLOQ samples were 63 days post-dose for serum. The median time to achieve complete elimination as the 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. The estimated elimination half-life of ELEVIDYS vector genome in the serum is approximately 12 hours, and the majority of the drug is expected to be cleared from the serum by 1-week post-dose. In the excreta, the estimated elimination half-life of ELEVIDYS vector genome is 40 hours, 55 hours, and 60 hours in the urine, feces, and saliva, respectively. As an AAV-based gene therapy that consists of a protein capsid containing the transgene DNA genome of interest, ELEVIDYS capsid proteins are broken down through proteasomal degradation following AAV entry into target cells. As such, ELEVIDYS is not likely to exhibit the drug-drug interaction potential mediated by known drug metabolizing enzymes (cytochrome P450-based) and drug transporters.
12.6 Immunogenicity
The observed incidence of anti-AAVrh74 antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-AAVrh74 antibodies in the studies described below with the incidence of anti-AAVrh74 antibodies in other studies.
In ELEVIDYS clinical studies, patients were required to have baseline anti-AAVrh74 total binding antibodies of ≤1:400, measured using an investigational total binding antibody enzyme-linked immunosorbent assay (ELISA), and only patients with baseline anti-AAVrh74 total binding antibodies <1:400 were enrolled in those studies. The safety and efficacy of ELEVIDYS in patients with elevated anti-AAVrh74 total binding antibody titer (≥1:400) have not been evaluated [see Clinical Studies (14)].
Across clinical studies evaluating a total of 84 patients, elevated anti-AAVrh74 total binding antibodies titers were observed in all patients following a one-time ELEVIDYS infusion. Anti-AAVrh74 total binding antibody titers reached at least 1:409,600 in every subject, and the maximum titers exceeded 1:26,214,400 in certain subjects. The safety of re-administration of ELEVIDYS or any other AAVrh74 vector-based gene therapy in the presence of high anti-AAVrh74 total binding antibody titer has not been evaluated in humans [see Warnings and Precautions (5.4)].
13. Nonclinical Toxicology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No animal studies have been performed to evaluate the effects of ELEVIDYS on carcinogenicity, mutagenesis, or impairment of fertility.
14. Clinical Studies
Accelerated approval was primarily based on data from Study 1 and Study 2 described below.
Study 1 is an ongoing multi-center study including:
- Part 1: a 48-week, randomized, double-blind, placebo-controlled period
- Part 2: a 48-week period that began following completion of Part 1. Patients who received placebo during Part 1 were treated with ELEVIDYS, and patients treated with ELEVIDYS during Part 1 received placebo.
The study population consisted of male ambulatory DMD patients (N=41) aged 4 through 7 years with either a confirmed frameshift mutation, or a premature stop codon mutation between exons 18 to 58 in the DMD gene.
Patients were randomized 1:1 to receive either ELEVIDYS (N=20) or placebo (N=21), as a single intravenous infusion via a peripheral limb. Randomization was stratified by age (i.e., aged 4 to 5 years vs. aged 6 to 7 years). In the ELEVIDYS group, eight patients received 1.33 × 1014 vg/kg of ELEVIDYS, and 12 patients received lower doses. Key demographic and baseline characteristics are presented in Table 6 below.
Table 6: Key Demographic and Baseline Characteristics (Part 1)
Characteristic | All
(n=41) | ELEVIDYS
(n=20) | Placebo
(n=21) | ELEVIDYS
Aged 4 through 5- year-old subgroup
(n=8) | Placebo
Aged 4 through 5- year-old subgroup
(n=8) |
Race group
White (%)
| 73.2
|
65
|
81
| 75
|
100
|
| Mean age [range] (years)
| 6.27
[4.34 – 7.98]
| 6.29
[4.47 – 7.85]
| 6.24
[4.34 – 7.98]
| 4.98
[4.47 – 5.39]
| 5.15
[4.93 – 5.91]
|
| Mean weight [range] (kg)
| 22.4
[15.0 – 34.5]
| 23.3
[18.0 – 34.5]
| 21.6
[15.0 – 30.0]
| 20.1
[18.0 – 23.5]
| 19.8
[15.0 – 21.5]
|
| Mean NSAA total score [range]
| 21.2
[13 – 29]
| 19.8
[13 – 26]
| 22.6
[15 – 29]
| 20.1
[17 – 23]
| 20.4
[15 – 24]
|
| Mean time to rise from floor [range] (seconds)
| 4.3
[2.7 – 10.4]
| 5.1
[3.2 – 10.4]
| 3.6
[2.7 – 4.8]
| 3.9
[3.2 – 5.2]
| 3.8
[3.2 – 10.4]
|
All subjects were on a stable dose of corticosteroids for DMD for at least 12 weeks prior to ELEVIDYS infusion. All randomized subjects had baseline anti-AAVrh74 antibody titers <1:400 as determined by an investigational total binding antibody ELISA.
One day prior to treatment with ELEVIDYS or placebo, the subject's background dose of corticosteroid for DMD was increased to at least 1 mg/kg of a corticosteroid (prednisone equivalent) daily and was continued at this level for at least 60 days after the infusion, unless earlier tapering was clinically indicated.
The primary objectives of Study 1 were to evaluate expression of ELEVIDYS micro-dystrophin in skeletal muscle, and to evaluate the effect of ELEVIDYS on the North Star Ambulatory Assessment (NSAA) total score.
Results of ELEVIDYS micro-dystrophin measured by western blot are presented in Table 5
[see Clinical Pharmacology (12.2)].
The change in NSAA total score was assessed from baseline to Week 48 after infusion of ELEVIDYS or placebo. The difference between the ELEVIDYS and placebo groups was not statistically significant (p=0.37). The least squares (LS) mean changes in NSAA total score from baseline to Week 48 was 1.7 (standard error [SE]: 0.6) points for the ELEVIDYS group and 0.9 (SE: 0.6) points for the placebo group.
Exploratory subgroup analyses showed that for subjects aged 4 through 5 years, the LS mean changes (SE) in NSAA total score from baseline to Week 48 were 4.3 (0.7) points for the ELEVIDYS group, and 1.9 (0.7) points for the placebo group, a numerical advantage for ELEVIDYS. For subjects aged 6 through 7 years, the LS mean changes (SE) in NSAA total score from baseline to Week 48 were -0.2 (0.7) points for the ELEVIDYS group and 0.5 (0.7) points for the placebo group, a numerical disadvantage for ELEVIDYS.
Study 2 is an ongoing, open-label, multi-center study which includes a cohort of 20 ambulatory male DMD subjects aged 4 through 7 years. All 20 subjects have a confirmed frameshift mutation, canonical splice site mutation, or premature stop codon mutation in the DMD gene.
At study entry, 75% of subjects were white with a mean age of 5.81 years (range: 4.38 to 7.94), mean weight of 21.2 kg (range: 15.2 to 33.1), mean NSAA total score of 22.1 points (range: 18 to 26), and mean time to rise from floor of 4.2 seconds (range: 2.4 to 8.2). Subjects received corticosteroids for DMD before infusion according to Table 1
[see Dosage and Administration (2.2)]. All subjects had baseline anti-AAVrh74 antibodies titers <1:400 as determined by the investigational total binding antibody ELISA and received a single intravenous infusion of 1.33 × 1014 vg/kg ELEVIDYS.
The primary objective of the study was to evaluate the effect of ELEVIDYS micro-dystrophin expression as measured by western blot. Results are presented in Table 5
[see Clinical Pharmacology (12.2)].
16. How is Elevidys supplied
16.1 How Supplied
ELEVIDYS is shipped frozen (≤ -60ºC [-76ºF]) in 10 mL vials.
ELEVIDYS is supplied as a customized kit to meet dosing requirements for each patient [see Dosage and Administration (2.1)]. Each kit contains:
- Ten (10) to seventy (70) single-dose vials of ELEVIDYS
- One alcohol wipe per vial
Each ELEVIDYS pack may contain a maximum of two different drug product lots.
The total number of vials in each kit corresponds to the dosing requirement for the individual patient, based on the patient's body weight, and is specified on the package [see Dosage and Administration (2.2)]. Each kit includes a specified number of ELEVIDYS vials (with a minimum of 10 vials for a patient with 10.0 – 10.4 kg body weight range, and a maximum of 70 vials for a patient with body weight of 69.5 kg and above).
Kit sizes and National Drug Codes (NDC) are provided in Table 7.
Table 7: ELEVIDYS Multi-vial Kits
Patient Weight
(kg) | Total Vials per Kit | Total Dose Volume per Kit (mL) | NDC Number |
| 10.0 – 10.4
| 10
| 100
| 60923-501-10
|
| 10.5 – 11.4
| 11
| 110
| 60923-502-11
|
| 11.5 – 12.4
| 12
| 120
| 60923-503-12
|
| 12.5 – 13.4
| 13
| 130
| 60923-504-13
|
| 13.5 – 14.4
| 14
| 140
| 60923-505-14
|
| 14.5 – 15.4
| 15
| 150
| 60923-506-15
|
| 15.5 – 16.4
| 16
| 160
| 60923-507-16
|
| 16.5 – 17.4
| 17
| 170
| 60923-508-17
|
| 17.5 – 18.4
| 18
| 180
| 60923-509-18
|
| 18.5 – 19.4
| 19
| 190
| 60923-510-19
|
| 19.5 – 20.4
| 20
| 200
| 60923-511-20
|
| 20.5 – 21.4
| 21
| 210
| 60923-512-21
|
| 21.5 – 22.4
| 22
| 220
| 60923-513-22
|
| 22.5 – 23.4
| 23
| 230
| 60923-514-23
|
| 23.5 – 24.4
| 24
| 240
| 60923-515-24
|
| 24.5 – 25.4
| 25
| 250
| 60923-516-25
|
| 25.5 – 26.4
| 26
| 260
| 60923-517-26
|
| 26.5 – 27.4
| 27
| 270
| 60923-518-27
|
| 27.5 – 28.4
| 28
| 280
| 60923-519-28
|
| 28.5 – 29.4
| 29
| 290
| 60923-520-29
|
| 29.5 – 30.4
| 30
| 300
| 60923-521-30
|
| 30.5 – 31.4
| 31
| 310
| 60923-522-31
|
| 31.5 – 32.4
| 32
| 320
| 60923-523-32
|
| 32.5 – 33.4
| 33
| 330
| 60923-524-33
|
| 33.5 – 34.4
| 34
| 340
| 60923-525-34
|
| 34.5 – 35.4
| 35
| 350
| 60923-526-35
|
| 35.5 – 36.4
| 36
| 360
| 60923-527-36
|
| 36.5 – 37.4
| 37
| 370
| 60923-528-37
|
| 37.5 – 38.4
| 38
| 380
| 60923-529-38
|
| 38.5 – 39.4
| 39
| 390
| 60923-530-39
|
| 39.5 – 40.4
| 40
| 400
| 60923-531-40
|
| 40.5 – 41.4
| 41
| 410
| 60923-532-41
|
| 41.5 – 42.4
| 42
| 420
| 60923-533-42
|
| 42.5 – 43.4
| 43
| 430
| 60923-534-43
|
| 43.5 – 44.4
| 44
| 440
| 60923-535-44
|
| 44.5 – 45.4
| 45
| 450
| 60923-536-45
|
| 45.5 – 46.4
| 46
| 460
| 60923-537-46
|
| 46.5 – 47.4
| 47
| 470
| 60923-538-47
|
| 47.5 – 48.4
| 48
| 480
| 60923-539-48
|
| 48.5 – 49.4
| 49
| 490
| 60923-540-49
|
| 49.5 – 50.4
| 50
| 500
| 60923-541-50
|
| 50.5 – 51.4
| 51
| 510
| 60923-542-51
|
| 51.5 – 52.4
| 52
| 520
| 60923-543-52
|
| 52.5 – 53.4
| 53
| 530
| 60923-544-53
|
| 53.5 – 54.4
| 54
| 540
| 60923-545-54
|
| 54.5 – 55.4
| 55
| 550
| 60923-546-55
|
| 55.5 – 56.4
| 56
| 560
| 60923-547-56
|
| 56.5 – 57.4
| 57
| 570
| 60923-548-57
|
| 57.5 – 58.4
| 58
| 580
| 60923-549-58
|
| 58.5 – 59.4
| 59
| 590
| 60923-550-59
|
| 59.5 – 60.4
| 60
| 600
| 60923-551-60
|
| 60.5 – 61.4
| 61
| 610
| 60923-552-61
|
| 61.5 – 62.4
| 62
| 620
| 60923-553-62
|
| 62.5 – 63.4
| 63
| 630
| 60923-554-63
|
| 63.5 – 64.4
| 64
| 640
| 60923-555-64
|
| 64.5 – 65.4
| 65
| 650
| 60923-556-65
|
| 65.5 – 66.4
| 66
| 660
| 60923-557-66
|
| 66.5 – 67.4
| 67
| 670
| 60923-558-67
|
| 67.5 – 68.4
| 68
| 680
| 60923-559-68
|
| 68.5 – 69.4
| 69
| 690
| 60923-560-69
|
| 69.5 and above
| 70
| 700
| 60923-561-70
|
A 10 mL single-dose vial carton for ELEVIDYS (NDC 60923-562-01) is not sold individually.
16.2 Storage and Handling
- 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 (36º F to 46º F) 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.
17. Patient Counseling Information
Inform caregivers that:
- ELEVIDYS can increase certain liver enzyme levels and cause acute serious liver injury. Patients will receive oral corticosteroid medication before and after infusion with ELEVIDYS. Weekly blood tests will be required to monitor liver enzyme levels for 3 months after treatment. Contact a healthcare provider immediately if the patient's skin and/or whites of the eyes appear yellowish, or if the patient misses a dose of corticosteroid or vomits it up [see Warnings and Precautions (5.1)].
- Immune-mediated myositis (an immune response affecting muscles) was observed in patients with a deletion mutation in the DMD gene that is contraindicated. Contact a physician immediately if the patient experiences any unexplained increased muscle pain, tenderness, or weakness, including difficulty swallowing, difficulty breathing or difficulty speaking, as these may be symptoms of myositis [see Warnings and Precautions (5.2)].
- Myocarditis (inflammation of the heart) has been observed within days following ELEVIDYS infusion. Weekly monitoring of troponin-I for the first month after treatment is required. Contact a healthcare provider immediately if the patient begins to experience chest pain and/or shortness of breath [see Warnings and Precautions (5.3)].
- Patient's immunizations should be up-to-date with current immunization guidelines prior to initiation of the corticosteroid regimen required before ELEVIDYS infusion. Vaccinations should be completed at least 4 weeks prior to initiation of the corticosteroid regimen [see Drug Interactions (7)].
- Due to the concomitant administration of corticosteroids, an infection (e.g., cold, flu, gastroenteritis, otitis media, bronchiolitis, etc.) before or after ELEVIDYS infusion could lead to more serious complications. Contact a healthcare provider immediately if symptoms suggestive of infection are observed (e.g., coughing, wheezing, sneezing, runny nose, sore throat, or fever).
- Vector shedding of ELEVIDYS occurs primarily through body waste. Practice proper hand hygiene, such as hand washing, when coming into direct contact with patient body waste. Place potentially contaminated materials that may have the patient's bodily fluids/waste in a sealable bag and dispose into regular trash. These precautions should be followed for one month after ELEVIDYS infusion.
Manufactured for: Sarepta Therapeutics, Inc.
Cambridge, MA 02142 USA
U.S. license number 2308
Principal Display Panel –Carton Kit Label
delandistrogene moxeparvovec-rokl
ELEVIDYS
1.33 x 1013
vector genomes/mL
Suspension for Infusion
For Intravenous Use
See enclosed prescribing information for dosage
and administration instructions.
Preservative-free
Discard unused
portion
Single patient use
Store unopened vials at ≤-60°C (-76°F) in
original carton.
Unopened vials can be refrigerated for up to
14 days at 2°C to 8°C (36°F to 46°F).
DO NOT REFREEZE
DO NOT SHAKE
Rx Only
Manufactured for Sarepta Therapeutics, Inc.,
Cambridge, MA 01242 USA
US License No. 2308
SAREPTA
THERAPEUTICS
Principal Display Panel -10 mL 10 count Carton Label
NDC: 60923-501-10
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
10.0 - 10.4 kg
Kit Contents:
10 x 10 mL vials
10 alcohol swabs
Principal Display Panel -10 mL 11 count Carton Label
NDC: 60923-502-11
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
10.5 - 11.4 kg
Kit Contents:
11 x 10 mL vials
11 alcohol swabs
Principal Display Panel -10 mL 12 count Carton Label
NDC: 60923-503-12
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
11.5 - 12.4 kg
Kit Contents:
12 x 10 mL vials
12 alcohol swabs
Principal Display Panel -10 mL 13 count Carton Label
NDC: 60923-504-13
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
12.5 - 13.4 kg
Kit Contents:
13 x 10 mL vials
13 alcohol swabs
Principal Display Panel -10 mL 14 count Carton Label
NDC: 60923-505-14
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
13.5 - 14.4 kg
Kit Contents:
14 x 10 mL vials
14 alcohol swabs
Principal Display Panel -10 mL 15 count Carton Label
NDC: 60923-506-15
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
14.5 - 15.4 kg
Kit Contents:
15 x 10 mL vials
15 alcohol swabs
Principal Display Panel -10 mL 16 count Carton Label
NDC: 60923-507-16
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
15.5 - 16.4 kg
Kit Contents:
16 x 10 mL vials
16 alcohol swabs
Principal Display Panel -10 mL 17 count Carton Label
NDC: 60923-508-17
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
16.5 - 17.4 kg
Kit Contents:
17 x 10 mL vials
17 alcohol swabs
Principal Display Panel -10 mL 18 count Carton Label
NDC: 60923-509-18
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
17.5 - 18.4 kg
Kit Contents:
18 x 10 mL vials
18 alcohol swabs
Principal Display Panel -10 mL 19 count Carton Label
NDC: 60923-510-19
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
18.5 - 19.4 kg
Kit Contents:
19 x 10 mL vials
19 alcohol swabs
Principal Display Panel -10 mL 20 count Carton Label
NDC: 60923-511-20
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
19.5 - 20.4 kg
Kit Contents:
20 x 10 mL vials
20 alcohol swabs
Principal Display Panel -10 mL 21 count Carton Label
NDC: 60923-512-21
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
20.5 - 21.4 kg
Kit Contents:
21 x 10 mL vials
21 alcohol swabs
Principal Display Panel -10 mL 22 count Carton Label
NDC: 60923-513-22
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
21.5 - 22.4 kg
Kit Contents:
22 x 10 mL vials
22 alcohol swabs
Principal Display Panel -10 mL 23 count Carton Label
NDC: 60923-514-23
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
22.5 - 23.4 kg
Kit Contents:
23 x 10 mL vials
23 alcohol swabs
Principal Display Panel -10 mL 24 count Carton Label
NDC: 60923-515-24
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
23.5 - 24.4 kg
Kit Contents:
24 x 10 mL vials
24 alcohol swabs
Principal Display Panel -10 mL 25 count Carton Label
NDC: 60923-516-25
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
24.5 - 25.4 kg
Kit Contents:
25 x 10 mL vials
25 alcohol swabs
Principal Display Panel -10 mL 26 count Carton Label
NDC: 60923-517-26
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
25.5 - 26.4 kg
Kit Contents:
26 x 10 mL vials
26 alcohol swabs
Principal Display Panel -10 mL 27 count Carton Label
NDC: 60923-518-27
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
26.5 - 27.4 kg
Kit Contents:
27 x 10 mL vials
27 alcohol swabs
Principal Display Panel -10 mL 28 count Carton Label
NDC: 60923-519-28
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
27.5 - 28.4 kg
Kit Contents:
28 x 10 mL vials
28 alcohol swabs
Principal Display Panel -10 mL 29 count Carton Label
NDC: 60923-520-29
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
28.5 - 29.4 kg
Kit Contents:
29 x 10 mL vials
29 alcohol swabs
Principal Display Panel -10 mL 30 count Carton Label
NDC: 60923-521-30
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
29.5 - 30.4 kg
Kit Contents:
30 x 10 mL vials
30 alcohol swabs
Principal Display Panel -10 mL 31 count Carton Label
NDC: 60923-522-31
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
30.5 - 31.4 kg
Kit Contents:
31 x 10 mL vials
31 alcohol swabs
Principal Display Panel -10 mL 32 count Carton Label
NDC: 60923-523-32
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
31.5 - 32.4 kg
Kit Contents:
32 x 10 mL vials
32 alcohol swabs
Principal Display Panel -10 mL 33 count Carton Label
NDC: 60923-524-33
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
32.5 - 33.4 kg
Kit Contents:
33 x 10 mL vials
33 alcohol swabs
Principal Display Panel -10 mL 34 count Carton Label
NDC: 60923-525-34
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
33.5 - 34.4 kg
Kit Contents:
34 x 10 mL vials
34 alcohol swabs
Principal Display Panel -10 mL 35 count Carton Label
NDC: 60923-526-35
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
34.5 - 35.4 kg
Kit Contents:
35 x 10 mL vials
35 alcohol swabs
Principal Display Panel -10 mL 36 count Carton Label
NDC: 60923-527-36
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
35.5 - 36.4 kg
Kit Contents:
36 x 10 mL vials
36 alcohol swabs
Principal Display Panel -10 mL 37 count Carton Label
NDC: 60923-528-37
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
36.5 - 37.4 kg
Kit Contents:
37 x 10 mL vials
37 alcohol swabs
Principal Display Panel -10 mL 38 count Carton Label
NDC: 60923-529-38
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
37.5 - 38.4 kg
Kit Contents:
38 x 10 mL vials
38 alcohol swabs
Principal Display Panel -10 mL 39 count Carton Label
NDC: 60923-530-39
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
38.5 - 39.4 kg
Kit Contents:
39 x 10 mL vials
39 alcohol swabs
Principal Display Panel -10 mL 40 count Carton Label
NDC: 60923-531-40
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
39.5 - 40.4 kg
Kit Contents:
40 x 10 mL vials
40 alcohol swabs
Principal Display Panel -10 mL 41 count Carton Label
NDC: 60923-532-41
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
40.5 - 41.4 kg
Kit Contents:
41 x 10 mL vials
41 alcohol swabs
Principal Display Panel -10 mL 42 count Carton Label
NDC: 60923-533-42
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
41.5 - 42.4 kg
Kit Contents:
42 x 10 mL vials
42 alcohol swabs
Principal Display Panel -10 mL 43 count Carton Label
NDC: 60923-534-43
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
42.5 - 43.4 kg
Kit Contents:
43 x 10 mL vials
43 alcohol swabs
Principal Display Panel -10 mL 44 count Carton Label
NDC: 60923-535-44
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
43.5 - 44.4 kg
Kit Contents:
44 x 10 mL vials
44 alcohol swabs
Principal Display Panel -10 mL 45 count Carton Label
NDC: 60923-536-45
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
44.5 - 45.4 kg
Kit Contents:
45 x 10 mL vials
45 alcohol swabs
Principal Display Panel -10 mL 46 count Carton Label
NDC: 60923-537-46
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
45.5 - 46.4 kg
Kit Contents:
46 x 10 mL vials
46 alcohol swabs
Principal Display Panel -10 mL 47 count Carton Label
NDC: 60923-538-47
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
46.5 - 47.4 kg
Kit Contents:
47 x 10 mL vials
47 alcohol swabs
Principal Display Panel -10 mL 48 count Carton Label
NDC: 60923-539-48
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
47.5 - 48.4 kg
Kit Contents:
48 x 10 mL vials
48 alcohol swabs
Principal Display Panel -10 mL 49 count Carton Label
NDC: 60923-540-49
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
48.5 - 49.4 kg
Kit Contents:
49 x 10 mL vials
49 alcohol swabs
Principal Display Panel -10 mL 50 count Carton Label
NDC: 60923-541-50
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
49.5 - 50.4 kg
Kit Contents:
50 x 10 mL vials
50 alcohol swabs
Principal Display Panel –Carton Kit Label
delandistrogene moxeparvovec-rokl
ELEVIDYS
1.33 x 1013
vector genomes/mL
Suspension for Infusion
For Intravenous Use
See enclosed prescribing information for dosage
and administration instructions.
Preservative-free
Discard unused
portion
Single patient use
Store unopened vials at ≤-60°C (-76°F) in
original carton.
Unopened vials can be refrigerated for up to
14 days at 2°C to 8°C (36°F to 46°F).
DO NOT REFREEZE
DO NOT SHAKE
Rx Only
Manufactured for Sarepta Therapeutics, Inc.,
Cambridge, MA 01242 USA
US License No. 2308
Principal Display Panel –Carton Kit Label
delandistrogene moxeparvovec-rokl
ELEVIDYS
1.33 x 1013
vector genomes/mL
Suspension for Infusion
For Intravenous Use
See enclosed prescribing information for dosage
and administration instructions.
Preservative-free
Discard unused
portion
Single patient use
Store unopened vials at ≤-60°C (-76°F) in
original carton.
Unopened vials can be refrigerated for up to
14 days at 2°C to 8°C (36°F to 46°F).
DO NOT REFREEZE
DO NOT SHAKE
Rx Only
Manufactured for Sarepta Therapeutics, Inc.,
Cambridge, MA 01242 USA
US License No. 2308
Principal Display Panel –Vial Label
delandistrogene moxeparvovec-rokl
ELEVIDYS
1.33 x 1013
vector genomes/mL
Suspension for infusion. Single-dose vial 10 mL.
For intravenous use. Store at ≤ -60°C (-76°F).
Do not refreeze. Do not shake.
Mfg. for: Sarepta Therapeutics, Inc.,
Cambridge, MA 01242 USA
US License No. 2308
Rx Only
NDC 60923-562-01
Principal Display Panel -10 mL 51 count Carton Label
NDC: 60923-542-51
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
50.5 - 51.4 kg
Kit Contents:
51 x 10 mL vials
51 alcohol swabs
Principal Display Panel -10 mL 52 count Carton Label
NDC: 60923-543-52
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
51.5 - 52.4 kg
Kit Contents:
52 x 10 mL vials
52 alcohol swabs
Principal Display Panel -10 mL 53 count Carton Label
NDC: 60923-544-53
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
52.5 - 53.4 kg
Kit Contents:
53 x 10 mL vials
53 alcohol swabs
Principal Display Panel -10 mL 54 count Carton Label
NDC: 60923-545-54
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
53.5 - 54.4 kg
Kit Contents:
54 x 10 mL vials
54 alcohol swabs
Principal Display Panel -10 mL 55 count Carton Label
NDC: 60923-546-55
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
54.5 - 55.4 kg
Kit Contents:
55 x 10 mL vials
55 alcohol swabs
Principal Display Panel -10 mL 56 count Carton Label
NDC: 60923-547-56
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
55.5 - 56.4 kg
Kit Contents:
56 x 10 mL vials
56 alcohol swabs
Principal Display Panel -10 mL 57 count Carton Label
NDC: 60923-548-57
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
56.5 - 57.4 kg
Kit Contents:
57 x 10 mL vials
57 alcohol swabs
Principal Display Panel -10 mL 58 count Carton Label
NDC: 60923-549-58
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
57.5 - 58.4 kg
Kit Contents:
58 x 10 mL vials
58 alcohol swabs
Principal Display Panel -10 mL 59 count Carton Label
NDC: 60923-550-59
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
58.5 - 59.4 kg
Kit Contents:
59 x 10 mL vials
59 alcohol swabs
Principal Display Panel -10 mL 60 count Carton Label
NDC: 60923-551-60
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
59.5 - 60.4 kg
Kit Contents:
60 x 10 mL vials
60 alcohol swabs
Principal Display Panel -10 mL 61 count Carton Label
NDC: 60923-552-61
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
60.5 - 61.4 kg
Kit Contents:
61 x 10 mL vials
61 alcohol swabs
Principal Display Panel -10 mL 62 count Carton Label
NDC: 60923-553-62
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
61.5 - 62.4 kg
Kit Contents:
62 x 10 mL vials
62 alcohol swabs
Principal Display Panel -10 mL 63 count Carton Label
NDC: 60923-554-63
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
62.5 - 63.4 kg
Kit Contents:
63 x 10 mL vials
63 alcohol swabs
Principal Display Panel -10 mL 64 count Carton Label
NDC: 60923-555-64
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
63.5 - 64.4 kg
Kit Contents:
64 x 10 mL vials
64 alcohol swabs
Principal Display Panel -10 mL 65 count Carton Label
NDC: 60923-556-65
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
64.5 - 65.4 kg
Kit Contents:
65 x 10 mL vials
65 alcohol swabs
Principal Display Panel -10 mL 66 count Carton Label
NDC: 60923-557-66
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
65.5 - 66.4 kg
Kit Contents:
66 x 10 mL vials
66 alcohol swabs
Principal Display Panel -10 mL 67 count Carton Label
NDC: 60923-558-67
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
66.5 - 67.4 kg
Kit Contents:
67 x 10 mL vials
67 alcohol swabs
Principal Display Panel -10 mL 68 count Carton Label
NDC: 60923-559-68
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
67.5 - 68.4 kg
Kit Contents:
68 x 10 mL vials
68 alcohol swabs
Principal Display Panel -10 mL 69 count Carton Label
NDC: 60923-560-69
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
68.5 - 69.4 kg
Kit Contents:
69 x 10 mL vials
69 alcohol swabs
Principal Display Panel -10 mL 70 count Carton Label
NDC: 60923-561-70
delandistrogene
moxeparvovec-rokl
ELEVIDYS
Patient Weight:
69.5 kg and
above
Kit Contents:
70 x 10 mL vials
70 alcohol swabs
Principal Display Panel – 10 mL Vial Label
NDC: 60923-562-01
delandistrogene moxeparvovec-rokl
ELEVIDYS
1.33 x 1013 vector genomes/mL
Suspension for Infusion
For Intravenous Use
See enclosed prescribing information
for dosage and administration instructions.
Rx Only
Single-dose
1 vial
