Etranacogene Dezaparvovec

FDA Drug Information • Also known as: Hemgenix

Brand Names: Hemgenix
Dosage Form: KIT
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION HEMGENIX (etranacogene dezaparvovec-drlb) is an adeno-associated viral vector-based gene therapy for intravenous infusion after dilution. HEMGENIX is a non-replicating recombinant AAV5 containing a codon-optimized DNA sequence of the gain-of-function Padua variant of human Factor IX (variant R338L), under control of a liver-specific promotor 1 (LP1). HEMGENIX has a nominal concentration of 1 × 10 13 gc/mL. Each vial contains an extractable volume of no less than 10 mL of HEMGENIX and the following excipients: sucrose (50 mg/mL), polysorbate-20 (0.22 mg/mL), potassium chloride (0.2 mg/mL), potassium phosphate (0.2 mg/mL), sodium chloride (8 mg/mL), and sodium phosphate (1.2 mg/mL). HEMGENIX is sterile, clear and colorless suspension, and contains no preservative. After dilution, HEMGENIX should be clear and colorless suspension.

What Is Etranacogene Dezaparvovec Used For?

1 INDICATIONS AND USAGE HEMGENIX is an adeno-associated virus vector-based gene therapy indicated for treatment of adults with Hemophilia B (congenital Factor IX deficiency) who: Currently use Factor IX prophylaxis therapy, or Have current or historical life-threatening hemorrhage, or Have repeated, serious spontaneous bleeding episodes. HEMGENIX is an adeno-associated virus vector-based gene therapy indicated for the treatment of adults with Hemophilia B (congenital Factor IX deficiency) who: Currently use Factor IX prophylaxis therapy, or Have current or historical life-threatening hemorrhage, or Have repeated, serious spontaneous bleeding episodes.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For single-use intravenous infusion only. For patient selection: Perform Factor IX inhibitor titer testing. In case of a positive test result for human Factor IX inhibitors, perform a re-test within approximately 2 weeks. If both the initial test and re-test results are positive, do not administer HEMGENIX to this patient. Perform liver health assessments, including: Enzyme testing [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin)], Hepatic ultrasound and elastography. In case of radiological liver abnormalities and/or sustained liver enzyme elevations, consider a consultation with hepatologist to assess eligibility for HEMGENIX [see Warnings and Precautions (5.2) ] . For single-use intravenous infusion only. ( 2 ) Perform baseline testing to select patients, including testing for Factor IX inhibitor presence and liver health tests. ( 2.1 ) The recommended dose of HEMGENIX is 2 × 10 13 genome copies (gc) per kg of body weight. ( 2.1 ) Administer HEMGENIX as an intravenous infusion after dilution with 0.9% normal saline at a constant infusion rate of 500 ml/hour (8 mL/min). ( 2.1 ) 2.1 Dose The recommended dose of HEMGENIX is 2 × 10 13 genome copies (gc) per kilogram (kg) of body weight (or 2 mL/kg body weight) administered as an intravenous infusion after dilution with 0.9% sodium chloride solution (normal saline) [see Dosage and Administration (2.2) ] . Calculate the dose as follows: HEMGENIX dose (in mL) = patient body weight (in kilogram) × 2 The multiplication factor 2 represents the per kilogram dose (2 × 10 13 gc/kg) divided by the amount of genome copies per mL of the HEMGENIX solution (1 × 10 13 gc/mL). Number of HEMGENIX vials needed = HEMGENIX dose (in mL) divided by 10 (round up to next whole number of vials). The division factor 10 represents the extractable volume of HEMGENIX from each vial (10 mL). The total volume of the patient's HEMGENIX dose to be diluted may be less than the total volume of vials needed. Example calculation for 72 kg patient Patient Weight HEMGENIX dose (mL) (body weight multiplied by 2) Number of Vials needed [HEMGENIX dose (mL) divided by 10, then rounded up] 72 kg 144 mL 15 HEMGENIX can be administered only once. 2.2 Preparation The vials are for single-dose only. General precautions Prepare HEMGENIX using sterile technique under aseptic conditions, proper engineering controls (e.g., biological safety cabinet or isolator) and according to institutional policies. Do not expose HEMGENIX to the light of an ultraviolet radiation disinfection lamp. Confirm that the patient's identity matches with the patient-specific identifier number on the outer carton. Verify the required dose of HEMGENIX based on the patient's body weight. Confirm that the carton contains sufficient number of vials to prepare the diluted HEMGENIX patient-specific infusion bag. Parenteral drug products should be inspected visually for particulate...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥5%) reported in clinical studies were ALT elevations, headache, blood creatine kinase elevations, flu-like symptoms, infusion-related reactions, fatigue, malaise, and AST elevations. The following adverse reactions are discussed in greater detail in other sections of the label: Infusion related reactions [see Warnings and Precautions (5.1) ] . Hepatotoxicity [see Warnings and Precautions (5.2) ] . Immune-mediated neutralization of the AAV5 vector capsid [see Warnings and Precautions (5.3) ] . The most common adverse reactions (incidence ≥5%) were elevated ALT, headache, blood creatine kinase elevations, flu-like symptoms, infusion-related reactions, fatigue, malaise and elevated AST. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact CSL Behring at 1-866-915-6958 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 clinical practice. The safety of HEMGENIX was evaluated in two clinical studies (the first study enrolled 3 subjects and the second study 54 subjects). Both studies enrolled adult male subjects with moderately severe or severe Hemophilia B (N = 57), who received a single intravenous dose of 2 × 10 13 gc/kg body weight of HEMGENIX. All subjects entered a follow-up period of 5 years. No serious adverse reactions were reported [see Clinical Studies (14) ] . The most common adverse reactions observed in ≥5% of subjects post-dose are listed in Table 2: Table 2. Adverse Reactions (Incidence ≥5%) Following Treatment with HEMGENIX Adverse Reactions ≥5% Subjects (%) (N = 57) Alanine aminotransferase increased 24 (42%) Headache 10 (18%) Blood creatine kinase increased 24 (42%) Flu-like symptoms 8 (14%) Infusion-related reactions Infusion-related reaction: In 7 subjects symptoms occurred during infusion, in 12 subjects after infusion. Symptoms occurring in ≥ 5% of subjects were: Dizziness, Flu-like symptoms and Headache. Symptoms occurring in < 5% of subjects were: Abdominal pain, Abdominal discomfort, Chest discomfort, Chills, Eye pruritus, Fever (Pyrexia), Flushing, Hives (Urticaria), Infusion site reaction, and Tachycardia. Eleven subjects recovered on the day or day one after infusion. Eight subjects recovered within 8 days after infusion. (see below) 19 (33%) Hypersensitivity 2 1of 2 hypersensitivity reactions – 12 minutes after initiation of administration of HEMGENIX, the patient experienced high blood pressure, red eyes, feeling warm, dizziness, coughing, dyspnea, elevated heart rate, shivering, and leg cramps. Infusion was stopped and not restarted. Only 10% of the HEMGENIX dose was administered. The patient recovered on the same day after treatment with intravenous diphenhydramine and intramuscular epinephrine. 2 of 2 hypersensitivity reactions – 10 minutes after initiation of administration of HEMGENIX, the patient experienced itching, tightness of throat, and swelling of the right side of the neck. The HEMGENIX dose was not interrupted and administered in full. All symptoms resolved on the same day without treatment. (4%) Fatigue 7 (12%) Aspartate aminotransferase increased 24 (42%) Nausea 4 (7%) Malaise 7 (12%) Infusion-related reactions were observed in 19 subjects. Infusions were temporarily interrupted in 3 subjects and resumed at a slower infusion rate after treatment with antihistamines and/or corticosteroids. In one subject, infusion was stopped and not resumed (see footnote of Table 2 ). There were 24 subjects who had elevated ALT values from Day 8 to 731 post-administration. Five subjects had ALT elevations >2-3× ULN (range = 89 IU/L – 130 IU/L), one subject had an ALT elevation > 3-5× ULN (193 IU/L) and one subject had an ALT elevation > 5× ULN (275 IU/L). The...

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary HEMGENIX is not intended for administration in women. No adverse effects on mating rate and fertility indices or fetal weights were observed in healthy naïve female mice mated with healthy male mice that were intravenously administered a predecessor of HEMGENIX product 6 days prior to mating. Vector DNA was not detected in the uterus, placenta, or fetus. In the United States general population, the estimated background risk 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 HEMGENIX is supplied as sterile, preservative-free, clear, and colorless suspension. HEMGENIX has a nominal concentration of 1 × 10 13 gc/mL. HEMGENIX is provided as a customized kit to meet dosing requirements for each patient [see Dosage and Administration (2.1) ], with each kit containing 10 (ten) to 48 (forty-eight) single-use vials (NDC 0053-0099-01), each with an extractable volume of no less than 10 mL of HEMGENIX (see 5 ) . The total number of vials in each kit corresponds to the dosing requirement for the individual patient depending on the patient`s body weight [se e Dosage and Administration (2.1) ] . The customized kit is accompanied with patient`s specific identifier number (Lot) on the outer carton. Each HEMGENIX kit may contain different drug product lots. Kit sizes and National Drug Codes (NDC) are provided in Table 5: Table 5. HEMGENIX Multi-Vial Kits Total Number of Vials per Kit Patient Body Weight (kg) Total Volume per Kit (mL) NDC Number 10 46-50 100 0053-0100-10 11 51-55 110 0053-0110-11 12 56-60 120 0053-0120-12 13 61-65 130 0053-0130-13 14 66-70 140 0053-0140-14 15 71-75 150 0053-0150-15 16 76-80 160 0053-0160-16 17 81-85 170 0053-0170-17 18 86-90 180 0053-0180-18 19 91-95 190 0053-0190-19 20 96-100 200 0053-0200-20 21 101-105 210 0053-0210-21 22 106-110 220 0053-0220-22 23 111-115 230 0053-0230-23 24 116-120 240 0053-0240-24 25 121-125 250 0053-0250-25 26 126-130 260 0053-0260-26 27 131-135 270 0053-0270-27 28 136-140 280 0053-0280-28 29 141-145 290 0053-0290-29 30 146-150 300 0053-0300-30 31 151-155 310 0053-0310-31 32 156-160 320 0053-0320-32 33 161-165 330 0053-0330-33 34 166-170 340 0053-0340-34 35 171-175 350 0053-0350-35 36 176-180 360 0053-0360-36 37 181-185 370 0053-0370-37 38 186-190 380 0053-0380-38 39 191-195 390 0053-0390-39 40 196-200 400 0053-0400-40 41 201-205 410 0053-0410-41 42 206-210 420 0053-0420-42 43 211-215 430 0053-0430-43 44 216-220 440 0053-0440-44 45 221-225...

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.