Home › Drugs › Delandistrogene Moxeparvovec-Rokl

Delandistrogene Moxeparvovec-Rokl

FDA Drug Information • Also known as: Elevidys

Brand Names
Elevidys
Route
INTRAVENOUS
Dosage Form
KIT
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: ACUTE SERIOUS LIVER INJURY AND ACUTE LIVER FAILURE Acute serious liver injury, including life-threatening and fatal acute liver failure, has occurred with ELEVIDYS [see Warnings and Precautions ( 5.1 )]. Patients with preexisting liver impairment may be at higher risk [see Warnings and Precautions ( 5.1 )]. Prior to infusion, assess liver function by clinical examination and laboratory testing. Administer systemic corticosteroids before and after ELEVIDYS infusion. Continue to monitor liver function weekly for the first 3 months after infusion and continue until results are unremarkable [see Dosage and Administration (2.1, 2.2, 2.4)]. Instruct patients to maintain proximity to an appropriate healthcare facility, as determined by the healthcare provider, for at least 2 months following ELEVIDYS infusion [see Dosage and Administration ( 2.1 )]. Obtain prompt consultation with a specialist (e.g., gastroenterologist or hepatologist) if acute serious liver injury or impending acute liver failure is suspected [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.1 )]. WARNING: ACUTE SERIOUS LIVER INJURY AND ACUTE LIVER FAILURE See full prescribing information for complete boxed warning. Acute serious liver injury, including life-threatening and fatal acute liver failure, has occurred with ELEVIDYS. ( 5.1 ) Patients with preexisting liver impairment may be at higher risk. ( 5.1 ) Prior to infusion, assess liver function by clinical examination and laboratory testing. Administer systemic corticosteroids before and after ELEVIDYS infusion. Continue to monitor liver function weekly for the first 3 months after infusion and continue until results are unremarkable. ( 2.1 , 2.2 , 2.4 ) Instruct patients to maintain proximity to an appropriate healthcare facility, as determined by the healthcare provider, for at least 2 months following ELEVIDYS infusion. ( 2.1 ) Obtain prompt consultation with a specialist (e.g., gastroenterologist or hepatologist) if acute serious liver injury or impending acute liver failure is suspected. ( 2.2 , 5.1 )

Description

11 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 ×10 13 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, with a pH of 8.0 ± 0.3.

What Is Delandistrogene Moxeparvovec-Rokl Used For?

1 INDICATIONS AND USAGE ELEVIDYS is indicated for the treatment of patients 4 years of age and older with Duchenne muscular dystrophy (DMD), who are ambulatory and have a confirmed mutation in the DMD gene [see Clinical Pharmacology ( 12.2 ), Clinical Studies ( 14 )] . ELEVIDYS is an adeno-associated virus vector-based gene therapy indicated for the treatment of patients 4 years of age and older with Duchenne muscular dystrophy (DMD) who are ambulatory and have a confirmed mutation in the DMD gene. ( 1 , 12.2 , 14 ) 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. 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.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For single-dose intravenous infusion only. ELEVIDYS is for single-dose intravenous infusion only. Select patients for treatment with ELEVIDYS with anti-AAVrh74 total binding antibody titers <1:400. ( 2.1 ) Postpone in patients with active or recent (within 4 weeks) infections. ( 2.1 ) Assess liver function, platelet counts and troponin-I before ELEVIDYS infusion. ( 2.1 ) Recommended dosage: 10 to 70 kg: 1.33 × 10 14 vector genomes (vg) per kg of body weight; 70 kg or greater: 9.31 × 10 15 vg. ( 2.2 ) One day prior to infusion, initiate a corticosteroid regimen for a minimum of 60 days. Recommend modifying corticosteroid dose for patients with liver function abnormalities. ( 2.2 ) Administer as an intravenous infusion over 1-2 hours. Infuse at a rate of less than 10 mL/kg/hour. ( 2.4 ) 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 × 10 14 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 × 10 15 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 × 10 14 vg/kg) divided by the amount of vector genome copies per mL of the ELEVIDYS suspension (1.33 × 10 13 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥5%) were vomiting and nausea, liver injury, pyrexia, thrombocytopenia, and troponin-I increased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sarepta Therapeutics, Inc., at 1-888-SAREPTA (1-888-727-3782) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 × 10 14 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. Table 3. Adverse reactions (Incidence ≥5%) following treatment with ELEVIDYS in Clinical Studies Adverse reactions ELEVIDYS (N=156) % a Includes: AST increased, ALT increased, GGT increased, GLDH increased, GLDH level abnormal, Hepatotoxicity, Hepatic enzyme increased, Hypertransaminasemia, Liver function test increased, Liver injury, Transaminases increased, Blood bilirubin increased b Includes: Thrombocytopenia, Platelet count decreased c Transient, mild, asymptomatic decrease in platelet counts d Includes: Troponin I increased, Troponin increased, Troponin I abnormal Vomiting 65 Nausea 43 Liver injury a 40 Pyrexia 28 Thrombocytopenia b c 8 Troponin-I increased d 8 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 × 10 14 vg/kg or placebo (N=62). Table 4 below presents the most frequent adverse reactions from Study 3 Part 1. Table 4. Adverse reactions occurring in ELEVIDYS-treated patients and at least twice more frequently than with placebo in Study 3 Part 1 a Includes: AST increased, ALT increased, GGT increased, GLDH increased, GLDH level abnormal, Hepatotoxicity, Hepatic enzyme increased, Hypertransaminasemia, Liver function test increased, Liver injury, Transaminases increased. b Includes: platelet count decreased, thrombocytopenia c Transient, mild, asymptomatic decrease in platelet counts Adverse reactions ELEVIDYS (N=63) % Placebo (N=62) % Vomiting 64 19 Nausea 40 13 Liver injury a 41 8 Pyrexia 32 24 Thrombocytopenia bc 3 0 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 :...

Drug Interactions

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.

Contraindications

4 CONTRAINDICATIONS 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 [see Warnings and Precautions ( 5.5 )] . 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. ( 4 )

Pregnancy and Breastfeeding

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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 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 . Table 10: 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...

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.