Limitations of Use:

ELEVIDYS is not recommended in patients with:

• Preexisting liver impairment (defined as gamma-glutamyl transferase [GGT] > 2 x upper limit of normal or total bilirubin > the upper limit of normal not due to Gilbert's syndrome) or active hepatic viral infection due to the high risk of acute serious liver injury and acute liver failure.
• Recent vaccination (within 4 weeks of treatment) due to immunogenicity and potential safety concerns.
• Active or recent (within 4 weeks) infections due to safety concerns.

2.1 Critical Dosing Information

• Instruct patients to maintain proximity to an appropriate healthcare facility, as determined by the healthcare provider, for at least 2 months following ELEVIDYS infusion.
• Prior to ELEVIDYS infusion:
  • Select patients for treatment with ELEVIDYS with anti-AAVrh74 total binding antibody titers <1:400. An FDA-authorized test for the detection of anti-AAVrh74 total binding antibodies is not currently available. Currently available tests may vary in accuracy and design.
  • Avoid ELEVIDYS administration in patients with elevated anti-AAVrh74 total binding antibody titers (≥1:400) [Clinical Pharmacology (12.6)].
  • Due to the increased risk of serious systemic immune response, postpone ELEVIDYS in patients with active or recent (within 4 weeks) infections [see Warnings and Precautions (5.2)].
  • Assess liver function (clinical examination and laboratory testing including aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), albumin, activated partial thromboplastin time (aPTT), international normalized ratio (INR), and total bilirubin) [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)].
• Do not re-administer ELEVIDYS.

2.2 Recommended 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 patients weighing less than 70 kg or 9.31 × 1015 vg total fixed dose for patients weighing 70 kg or greater.

For the number of vials required, refer to Table 10 [see How Supplied/Storage and Handling (16.1)].

Calculate the dose as follows:

ELEVIDYS dose (in mL) = patient body weight (rounded to the nearest 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.

Example: Calculation of volume needed for a 19.5 kg patient
           19.5 kg rounded to the nearest kilogram = 20 kg
           20 kg × 10 = 200 mL

Number of ELEVIDYS vials needed = 200 divided by 10, rounded to the nearest number of vials = 20 vials

Administer corticosteroids to reduce the risk of immune responses to the AAVrh74 vector after administration of ELEVIDYS [see Clinical Pharmacology (12.6)]. Start corticosteroids 1 day prior to ELEVIDYS infusion based on the schedule outlined in Table 1 below. Continue this regimen for a minimum of 60 days after the infusion, unless earlier tapering is clinically indicated.

Modify oral corticosteroid doses according to Table 2 for patients with liver function abnormalities (e.g., GGT >= 3 times baseline, total bilirubin > ULN) following ELEVIDYS infusion. Consider IV bolus corticosteroids instead of oral corticosteroids for GGT or bilirubin elevations that do not respond after 1 week of increased oral corticosteroids. Consult with a specialist experienced in immunosuppressive therapy for additional interventions as needed.

Obtain prompt consultation with a specialist (e.g., gastroenterologist or hepatologist) if acute serious liver injury or impending acute liver failure is suspected.

Taper the additional peri-ELEVIDYS corticosteroids for patients previously taking corticosteroids at baseline back to baseline dose over 2 weeks, or longer as needed. Taper the peri-ELEVIDYS corticosteroids for patients not previously taking corticosteroids at baseline back to no corticosteroids over 4 weeks, or longer as needed. Do not stop corticosteroids abruptly.

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 maximum or smaller stainless steel needles

Preparing ELEVIDYS infusion

1. 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.
   • Thawed ELEVIDYS is stable for up to 24 hours at room temperature (up to 25°C [77ºF]).
2. Inspect vials to ensure no ice crystals are present prior to preparation.
3. When thawed, swirl gently.
   • Do not shake.
   • Do not refreeze.
   • Do not place back in the refrigerator.
4. 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.
5. Remove the plastic flip-off cap from the vials and disinfect the rubber stopper with a sterilizing agent (e.g., alcohol wipes).
6. Withdraw 10 mL of ELEVIDYS from each vial provided in the customized ELEVIDYS kit (refer to Table 10).
   • 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.
7. Maintain syringes at room temperature prior to and during administration.

2.4 Administration

5.1 Acute Serious Liver Injury and Acute Liver Failure

Acute serious liver injury marked by elevations of liver enzymes (e.g., GGT, ALT) and total bilirubin and acute liver failure, has occurred with ELEVIDYS. Onset of the liver injury typically begins within 8 weeks after administration of ELEVIDYS. In non-ambulatory patients treated with ELEVIDYS, acute liver failure with fatal outcome has occurred in the clinical and post-marketing settings.

Life-threatening mesenteric vein thrombosis, complicated by bowel ischemia and necrosis, and portal hypertension have been reported following acute liver injury associated with ELEVIDYS in a non-ambulatory patient [see Adverse Reactions (6.2)].

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 or acute liver failure. 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, 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)]. Most cases resolved spontaneously or with systemic corticosteroids and resolved without clinical sequelae within 2 months.

Prior to ELEVIDYS administration, perform liver enzyme test [see Dosage and Administration (2.1)]. Monitor liver function (clinical examination, AST, ALT, GGT, albumin, aPTT, INR, and total bilirubin) weekly for the first 3 months following ELEVIDYS infusion. Continue monitoring if clinically indicated, until results are unremarkable (e.g., 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)]. Obtain prompt consultation with a specialist (e.g., gastroenterologist or hepatologist) if acute serious liver injury or impending acute liver failure is suspected.

5.2 Serious Infections

Increased susceptibility to serious infections may occur due to concomitant administration of corticosteroid regimen and additional immunosuppressants, and ELEVIDYS. Serious respiratory infections, including with fatal outcomes, have occurred in patients taking immunosuppressant corticosteroids required for ELEVIDYS administration [see Adverse Reactions (6.2)].

Monitor patients for signs and symptoms of infection before and after ELEVIDYS administration and treat appropriately. Administer immunizations according to best clinical practices and immunization guidelines prior to initiation of the corticosteroid regimen required before ELEVIDYS infusion [see Drug Interactions (7)].

Avoid administration of ELEVIDYS to patients with active infections.

5.3 Myocarditis

Acute, serious, life-threatening myocarditis and troponin-I elevations have been observed within 24 hours to more than 1 year following ELEVIDYS infusion [see Adverse Reactions (6.1)].

If a patient experiences myocarditis, those with pre-existing left ventricle ejection fraction (LVEF) impairment may be at higher risk of adverse outcomes. Patients with moderate to severe LVEF impairment have not been studied in clinical trials with ELEVIDYS.

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, until results return to near baseline levels or stabilize. 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 Infusion-related Reactions

Infusion-related reactions, including hypersensitivity reactions and anaphylaxis, have occurred during or up to several hours following ELEVIDYS administration. Closely monitor patients during and for at least 3 hours after the end of infusion for signs and symptoms of infusion-related reactions including tachycardia, tachypnea, lip swelling, difficulty breathing, nasal flaring, urticaria, flushing, lip pruritus, rash, cheilitis, vomiting, nausea, rigors and pyrexia.

ELEVIDYS should be administered in a setting where treatment for infusion-related reactions is immediately available.

In the event of an infusion-related reaction, administration of ELEVIDYS may be slowed or stopped based on the severity of the patient's clinical presentation. Administer treatment as needed to manage infusion-related reactions based on the severity of patient's signs and symptoms. [see Dosage and Administration (2.4)]. If the infusion was stopped, ELEVIDYS infusion may be restarted at a lower rate once patient's symptoms have resolved, at the discretion of the physician. Discontinue infusion for anaphylaxis.

5.5 Immune-mediated Myositis

Immune-mediated myositis, including serious and life-threatening events, has occurred approximately 1 month following ELEVIDYS infusion [see Adverse Reactions (6)]. Signs and symptoms include severe muscle weakness, including dysphagia, dyspnea, dysphonia, and hypophonia.

These immune reactions may be due to a T-cell based response against specific regions of the micro-dystrophin transgenic protein. Severe to life-threatening immune-mediated myositis has been reported in patients with deletions including portions of exons 1-17 and/or exons 59-71 of the DMD gene. ELEVIDYS is contraindicated in patients with any deletion in exon 8 and/or exon 9, including a deletion of any portion or the entirety of these exons, in the DMD gene due to the increased risk for a severe immune-mediated myositis reaction [see Contraindications (4)].

Regardless of genetic mutation, advise patients to contact a physician immediately if they experience any unexplained increased muscle pain, tenderness, or weakness, including dysphagia, dyspnea, dysphonia, or hypophonia as these may be symptoms of myositis. Consider additional immunomodulatory treatment based on patient's clinical presentation and medical history if these symptoms occur.

5.6 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 patients 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).

6.1 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 156 male patients with a confirmed mutation of the DMD gene in four clinical studies, including one completed open-label study, one ongoing open-label study, and two studies that included a double-blind, placebo-controlled period. Prior to ELEVIDYS infusion, patients in the ELEVIDYS treatment group had a mean age of 6.7 years (range: 3 to 20) and mean weight of 24.6 kg (range: 12.5 to 80.1). 144 patients received the recommended dose of 1.33 × 1014 vg/kg, and 12 received a lower dose. Table 3 below presents adverse reactions from these four 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), the first month (myocarditis, troponin-I increased) or within the first 2 months (immune-mediated myositis, liver injury). Vomiting may occur as early as on the day of the infusion.

In clinical trials, immune-mediated myositis was observed in 2 of 6 patients with deletion mutations involving exon 8 and/or 9 in the DMD gene [see Contraindications (4), and Warnings and Precautions (5.5)].

In the double-blind, placebo-controlled trial, Study 3 Part 1, patients 4 to 7 years of age (N=125) received either ELEVIDYS (N=63) at the recommended dose of 1.33 × 1014 vg/kg or placebo (N=62). Table 4 below presents the most frequent adverse reactions from Study 3 Part 1.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ELEVIDYS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hepatobiliary Disorders: Acute liver injury, acute liver failure, including fatal outcome and life-threatening mesenteric vein thrombosis [see Warnings and Precautions (5.1)]

Infections and Infestations: Bacterial and viral respiratory infections, including fatal outcome [see Warnings and Precautions (5.2)]

Immune System Disorders: Infusion-related reactions, including hypersensitivity reactions and anaphylaxis, have occurred during or up to several hours following ELEVIDYS administration [see Warnings and Precautions (5.4)].

Musculoskeletal and connective tissue disorders: Immune-mediated myositis [see Warnings and Precautions (5.5)].

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

The safety and effectiveness of ELEVIDYS for the treatment of Duchenne muscular dystrophy has been established in pediatric patients at least 4 years of age with a confirmed mutation in the DMD gene. The use of ELEVIDYS in pediatric patients was supported by evidence from three adequate and well controlled clinical studies which included 144 pediatric patients aged 4 years of age and older [see Adverse Reactions (6), 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. Treatment with ELEVIDYS 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 or acute liver failure [see Warnings and Precautions (5.1)].

In clinical trials, liver function test increase was commonly reported in patients following ELEVIDYS infusion [see Warnings and Precautions (5.1), Adverse Reactions (6.1)].

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 single-stranded DNA 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 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 micro-dystrophin protein expression predominantly in skeletal muscle (including diaphragm) and cardiac muscle. In clinical studies, muscle biopsy analyses have confirmed 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 92 patients who received ELEVIDYS in clinical studies, micro-dystrophin protein expression from muscle biopsies (gastrocnemius or biceps brachii) was quantified by western blot and localized by immunofluorescence staining (fiber intensity and percentage micro-dystrophin).

Micro-dystrophin expression (expressed as change from baseline) in ELEVIDYS-treated patients as measured by western blot was the primary objective of Study 1 and Study 2, and a key secondary objective for Study 3. Muscle biopsies were obtained at baseline prior to ELEVIDYS infusion and at Week 12 after ELEVIDYS infusion in all patients. The absolute quantity of 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 patients without DMD or Becker muscular dystrophy) in muscle biopsy samples. Study 1 and 2 results of patients receiving 1.33 × 1014 vg/kg ELEVIDYS are presented in Table 5.

In Study 3 Part 1, muscle biopsies were obtained at Week 12 in 31 patients. For the ELEVIDYS-treated patients, the mean micro-dystrophin expression at Week 12 was 34.3% (N=17, SD: 41.0%), compared to placebo patients of 0% (N=14, SD: 0%).

Assessment of micro-dystrophin levels can be meaningfully influenced by differences in sample processing, analytical technique, reference materials, and quantitation methodologies. Therefore, valid comparisons of micro-dystrophin measurements obtained from different assays cannot be made.

12.3 Pharmacokinetics

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.

Across clinical studies evaluating a total of 156 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 1:3200 in every patient, and the maximum titers exceeded 1:26,214,400 in certain patients. 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 (5.6)].

There is insufficient data to assess whether the observed anti-AAVrh74 antibodies titers have clinically significant effect on pharmacokinetics, pharmacodynamics, safety, and efficacy of ELEVIDYS.

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.

Study 1

Study 1 is a completed 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 4 through 5-year-old subgroup, the mean age, mean weight and mean NSAA total score (range) for the ELEVIDYS-treated patients (n=8) were 4.98 years, 20.1 kg and 20.1 (17-23), and for the placebo patients (n=8) were 5.15 years, 19.8 kg and 20.4 (15-24). 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.

All patients were on a stable dose of corticosteroids for DMD for at least 12 weeks prior to ELEVIDYS infusion. All randomized patients 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 patient'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 efficacy outcomes of Study 1 were to evaluate expression of micro-dystrophin in skeletal muscle, and to evaluate the effect of ELEVIDYS on the North Star Ambulatory Assessment (NSAA) total score.

Results of 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 patients 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 patients 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

Study 2 is an ongoing, open-label, multi-center study which includes 5 cohorts of 48 male DMD patients.

Patients in cohorts 1, 2 and 3 have a confirmed frameshift, splice site or premature stop codon mutation anywhere in the DMD gene, while patients in cohort 4 included patients with mutations in the DMD gene starting at or after exon 18. All patients in cohort 5 had mutations that partially or fully overlap with exons 1-17 in the DMD gene. Patients received corticosteroids for DMD before infusion according to Table 1 [see Dosage and Administration (2.2)]. All patients had baseline anti-AAVrh74 antibodies titers ≤1:400 as determined by the investigational total binding antibody ELISA. Patients received a single intravenous infusion of 1.33 × 1014 vg/kg ELEVIDYS if they weighed less than 70 kg or 9.31 × 1015 vg/kg total fixed dose if they weighed 70 kg or greater.

Cohorts 1, 2, 4 and 5a enrolled 40 ambulatory patients 3 to 12 years of age, with weights ranging from 12.5 to 50.5 kg, baseline mean NSAA total score of 20.3 (11 to 30), and mean time to rise from floor of 4.7 seconds (2.4 to 9.7). Cohorts 3 and 5b include 8 non-ambulatory patients 10 to 20 years of age, with weights ranging from 36.1 to 80.1 kg. Overall key demographics and key baseline characteristics by Cohort are presented in Table 7.

The efficacy outcome measure of the study was to evaluate the effect of micro-dystrophin expression as measured by western blot. Results are presented in Table 5 [see Clinical Pharmacology (12.2)].

Study 3

Study 3 is a multi-center, randomized, double-blind, placebo-controlled study in which 125 ambulatory male patients aged 4 through 7 years, with a confirmed frameshift, splice site, premature stop codon, or other disease-causing mutation in the DMD gene starting at or after exon 18, were dosed. Patients with exon 45 (inclusive), or in-frame deletions, in-frame duplications, and variants of uncertain significance (“VUS”), were excluded. Patients received corticosteroids for DMD before infusion according to Table 1 [see Dosage and Administration (2.2)]. All patients 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. Key demographic and baseline characteristics are presented in Table 8.

The efficacy outcome measure of the study was to evaluate the effect of ELEVIDYS on physical function as assessed by the NSAA total score. Key secondary outcome measures were to evaluate expression of micro-dystrophin in skeletal muscle, time to rise from floor, and time of 10-meter walk/run. Additional efficacy outcome measures included time of 100-meter walk/run, and time to ascend 4 steps. Results of 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 52 after infusion of ELEVIDYS or placebo. The difference between the ELEVIDYS (n=63) and placebo groups (n=61) was not statistically significant (p=0.24). The least squares (LS) mean changes in NSAA total score from baseline to Week 52 was 2.57 (95% confidence interval [CI]: 1.80, 3.34) points for the ELEVIDYS group and 1.92 (95% CI: 1.14, 2.70) points for the placebo group, with a LS mean difference from placebo of 0.65 (95% CI: -0.45, 1.74). Changes of clinical relevance were noted in three secondary efficacy endpoints, including time to rise from the floor, 10-meter walk/run and time to ascend 4 steps.

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 (2.2)]. 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 10.

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.

Inform patients or caregivers that:

• ELEVIDYS can increase certain liver enzyme levels and cause acute serious liver injury or acute liver failure, and death. Management of acute serious liver injury may require hospitalization. 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, if the patient misses a dose of corticosteroid or vomits it up, or if the patient experiences a change in mental status [see Warnings and Precautions (5.1)].
• Due to the concomitant administration of corticosteroids, an infection (e.g., cold, flu, gastroenteritis, otitis media, bronchiolitis, pneumonia, etc.) before or after ELEVIDYS infusion could lead to more serious complications, including death. Contact a healthcare provider immediately if symptoms suggestive of infection are observed (e.g., coughing, wheezing, sneezing, runny nose, sore throat, or fever) [see Warnings and Precautions (5.2)].
• Myocarditis (inflammation of the heart) has been observed within days to more than a year 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)].
• Infusion-related reactions including hypersensitivity and anaphylaxis have occurred during and after ELEVIDYS infusion. Possible symptoms of infusion-related reactions are fast heart rate, fast breathing, swollen lips, being short of breath, nostrils widening, hives, red and blotchy skin, itchy or inflamed lips, rash, vomiting, nausea, chills and fever. Contact a healthcare provider immediately if the patient experiences such a reaction [see Warnings and Precautions (5.4)].
• Immune-mediated myositis (an immune response affecting muscles) was observed in some patients following ELEVIDYS infusion. 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 (5.5)].
• 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)].
• 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

SAREPTA, SAREPTA THERAPEUTICS and ELEVIDYS are trademarks of Sarepta Therapeutics, Inc.
©2025 Sarepta Therapeutics, Inc.

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