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Etranacogene Dezaparvovec

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Sep.29.2023

Etranacogene Dezaparvovec

Indications/Dosage

Labeled

  • hemophilia B

Off-Label

    † Off-label indication

    For the treatment of hemophilia B in persons who currently use factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated serious spontaneous bleeding episodes

    Note: Etranacogene dezaparvovec has been designated orphan drug status by the FDA for the treatment of hemophilia B.

    Intravenous dosage

    Adults

    2 x 10 to the 13th power genome copies/kg (or 2 mL/kg) IV as a single dose. Monitor factor IX activity regularly (e.g., weekly for 3 months). It may take several weeks before improved hemostatic control becomes apparent after administration of etranacogene dezaparvovec. Continued treatment with exogenous human factor IX may be needed during the first weeks after etranacogene dezaparvovec administration.[68294]

    Therapeutic Drug Monitoring

    • Monitor factor IX activity regularly (e.g., weekly for 3 months), particularly when exogenous factor IX is administered. It may take several weeks before improved hemostatic control becomes apparent after administration of etranacogene dezaparvovec. Continued treatment with exogenous human factor IX may be needed during the first weeks after etranacogene dezaparvovec administration.[68294]
    • Monitor for development of factor IX inhibitors after administration of etranacogene dezaparvovec. Perform an assay that detects factor IX inhibitors if bleeding is not controlled, or plasma factor IX activity concentrations decrease.[68294]

    Maximum Dosage Limits

    • Adults

      2 x 1013 genome copies/kg (or 2 mL/kg) IV.

    • Geriatric

      2 x 1013 genome copies/kg (or 2 mL/kg) IV.

    • Adolescents

      Safety and efficacy have not been established.

    • Children

      Safety and efficacy have not been established.

    • Infants

      Safety and efficacy have not been established.

    • Neonates

      Safety and efficacy have not been established.

    Patients with Hepatic Impairment Dosing

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. No dosage adjustments were made in subjects with hepatic pathologies in clinical trials. The safety and efficacy of etranacogene dezaparvovec in subjects with advanced hepatic impairment have not been studied.[68294]

    Patients with Renal Impairment Dosing

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. No dosage adjustments were made in subjects with mild and moderate renal impairment in clinical trials. The safety and efficacy of etranacogene dezaparvovec in subjects with severe renal impairment and end-stage renal disease have not been studied.[68294]

    † Off-label indication
    Revision Date: 09/29/2023, 01:50:00 AM

    References

    68294 - Hemgenix (etranacogene dezaparvovec) suspension package insert. Kankakee, IL; CSL Behring LLC; 2022 Nov.

    How Supplied

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 101-105kg Suspension for Infusion (00053-0210) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 106-110kg Suspension for Infusion (00053-0220) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 111-115kg Suspension for Infusion (00053-0230) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 116-120kg Suspension for Infusion (00053-0240) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 121-125kg Suspension for Infusion (00053-0250) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 126-130kg Suspension for Infusion (00053-0260) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 131-135kg Suspension for Infusion (00053-0270) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 136-140kg Suspension for Infusion (00053-0280) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 141-145kg Suspension for Infusion (00053-0290) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 146-150kg Suspension for Infusion (00053-0300) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 151-155kg Suspension for Infusion (00053-0310) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 156-160kg Suspension for Infusion (00053-0320) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 161-165kg Suspension for Infusion (00053-0330) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 166-170kg Suspension for Infusion (00053-0340) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 171-175kg Suspension for Infusion (00053-0350) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 176-180kg Suspension for Infusion (00053-0360) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 181-185kg Suspension for Infusion (00053-0370) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 186-190kg Suspension for Infusion (00053-0380) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 191-195kg Suspension for Infusion (00053-0390) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 196-200kg Suspension for Infusion (00053-0400) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 201-205kg Suspension for Infusion (00053-0410) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 206-210kg Suspension for Infusion (00053-0420) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 211-215kg Suspension for Infusion (00053-0430) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 216-220kg Suspension for Infusion (00053-0440) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 221-225kg Suspension for Infusion (00053-0450) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 226-230kg Suspension for Infusion (00053-0460) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 231-235kg Suspension for Infusion (00053-0470) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 236-240kg Suspension for Infusion (00053-0480) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 46-50kg Suspension for Infusion (00053-0100) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 51-55kg Suspension for Infusion (00053-0110) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 56-60kg Suspension for Infusion (00053-0120) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 61-65kg Suspension for Infusion (00053-0130) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 66-70kg Suspension for Infusion (00053-0140) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 71-75kg Suspension for Infusion (00053-0150) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 76-80kg Suspension for Infusion (00053-0160) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 81-85kg Suspension for Infusion (00053-0170) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 86-90kg Suspension for Infusion (00053-0180) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 91-95kg Suspension for Infusion (00053-0190) (CSL Behring) null

    Etranacogene Dezaparvovec Suspension for injection

    HEMGENIX 96-100kg Suspension for Infusion (00053-0200) (CSL Behring) null

    Description/Classification

    Description

    Etranacogene dezaparvovec is an intravenous adeno-associated viral (AAV) vector-based gene therapy indicated for the treatment of hemophilia B in adults who currently use factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes. Efficacy of etranacogene dezaparvovec in persons with hemophilia B was evaluated in a prospective, open-label, single-dose, single-arm, multi-national clinical trial (n = 54). The main efficacy outcome was annualized bleeding rate (ABR) during months 7 to 18 after etranacogene dezaparvovec treatment compared to ABR during the lead-in period of at least 6 months. The estimated mean ABR during months 7 to 18 after treatment with etranacogene dezaparvovec was 1.9 bleeds/year compared to an estimated mean ABR of 4.1 bleeds/year during the lead-in period. Elevated hepatic enzymes have been reported with etranacogene dezaparvovec, and integration of liver-targeting AAV vector DNA into the genome may carry the theoretical risk of hepatocellular carcinoma development.[68294]

    Classifications

    • Blood and Blood Forming Organs
      • All Other Hematological Agents
        • Gene Therapy for Hemophilia B
    Revision Date: 09/29/2023, 01:50:00 AM

    References

    68294 - Hemgenix (etranacogene dezaparvovec) suspension package insert. Kankakee, IL; CSL Behring LLC; 2022 Nov.

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

    • Treat spills of etranacogene dezaparvovec with a virucidal agent with proven activity against non-enveloped viruses.
    • Dispose of unused product and disposable materials that may have come in contact with etranacogene dezaparvovec in accordance with local biosafety guidelines applicable for handling and disposal of the pharmaceutical waste.[68294]

    Route-Specific Administration

    Injectable Administration

    • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. If particulates, cloudiness, or discoloration is visible, do not use the vial(s). The diluted etranacogene dezaparvovec should be clear and colorless; do not use if particulates, cloudiness, or discoloration are visible.
    • Vials of etranacogene dezaparvovec are for single-use only.[68294]

    Intravenous Administration

    Preparation

    General Precautions:

    • Prepare etranacogene dezaparvovec using sterile technique under aseptic conditions, proper engineering controls (e.g., biological safety cabinet or isolator) and according to institutional policies.
    • Do not expose etranacogene dezaparvovec to the light of an ultraviolet radiation disinfection lamp.
    • Confirm that the patient's identity matches the patient-specific identifier number on the outer carton.
    • Verify the required dose of etranacogene dezaparvovec based on the patient's body weight.
    • Confirm that the carton contains enough vials to prepare the diluted etranacogene dezaparvovec infusion.[68294]

    Preparation of 0.9% Sodium Chloride Injection infusion bags:

    • Spike the 0.9% Sodium Chloride Injection infusion bag prior to dilution with applicable connector.
    • Connect a luer-lock syringe at the mixing adapter site of the applicable connector.
    • Withdraw the volume equal to the calculated etranacogene dezaparvovec dose (in mL) from the 500 mL infusion bag(s) of 0.9% Sodium Chloride Injection. The volume to withdraw and number of infusion bags will vary based on the patient body weight.
      • Less than 120 kg: one 500 mL 0.9% Sodium Chloride Injection infusion bag; withdraw 0.9% Sodium Chloride Injection equal to the total etranacogene dezaparvovec dose (in mL) from 1 infusion bag.
      • 120 kg or more: two 500 mL 0.9% Sodium Chloride Injection infusion bags; withdraw 0.9% Sodium Chloride Injection equal to the total etranacogene dezaparvovec dose (in mL) as one-half of the dose equivalent volume from each of the 2 infusion bags.[68294]

    Injection of etranacogene dezaparvovec into the 0.9% Sodium Chloride Injection infusion bags:

    • Dilute etranacogene dezaparvovec with 0.9% Sodium Chloride Injection only prior to administration.
    • Gently swirl the vials 3 times for approximately 10 seconds to homogenize the etranacogene dezaparvovec suspension. Do not shake the vials to avoid foaming.
    • Withdraw etranacogene dezaparvovec from each vial using a 20 G needle/vial adapter and syringe. Use a 20 mL luer-lock or larger syringe that is suitable for volume measuring and a needle; do not use filter needles during preparation of etranacogene dezaparvovec. Use a new needle/vial adapter and syringe for each etranacogene dezaparvovec vial.
    • Slowly add the required etranacogene dezaparvovec dose from the syringe(s) directly to the 0.9% Sodium Chloride Injection infusion bag(s) to bring the total volume in each infusion bag back to 500 mL. Do not add etranacogene dezaparvovec into the airspace of the bag to avoid foaming throughout this process.
    • Repeat the above steps with additional needles/vial adaptors and syringes to inject the total calculated etranacogene dezaparvovec infusion bag(s) required for the patient dose.
    • Gently invert the infusion bag(s) at least 3 times (about 10 seconds) to mix the solution and ensure even distribution of the diluted product. Do not shake the diluted etranacogene dezaparvovec infusion bags to avoid foaming.
    • Connect the infusion bag(s) to an infusion tube pre-filled with sterile 0.9% Sodium Chloride Injection to decrease the risk of spill and/or aerosol formation.
    • Transport the diluted etranacogene dezaparvovec infusion bag(s) in the transport container/bag protected from light to the administration site, avoiding any shaking or excessive agitation.
    • Storage: Infuse the diluted etranacogene dezaparvovec within 24 hours after dose preparation.[68294]

    Intravenous (IV) Infusion

    • Administer etranacogene dezaparvovec as a single-dose IV infusion through a peripheral venous catheter. Do not infuse through a central line or port.
    • Use an integrated (in-line) 0.2 micron filter made out of polyether sulfone (PES).
    • Connect the pre-filled IV infusion line to the main IV line that has been primed with sterile 0.9% Sodium Chloride Injection prior to use.
    • Infuse diluted etranacogene dezaparvovec at a constant IV infusion rate of 500 mL/hour (8 mL/minute). Do not administer as an IV push or bolus dose.
    • Do not infuse the diluted etranacogene dezaparvovec in the same IV line with any other products.
    • If an infusion reaction occurs during administration, the rate of the infusion may be reduced or stopped to manage the infusion reaction.
      • If the infusion is stopped, restart at a slower rate when the infusion reaction is resolved.
      • If the infusion rate needs to be decreased, or stopped and restarted, etranacogene dezaparvovec should be infused within 24 hours after the dose preparation.
    • After the entire content of the bag(s) is infused, flush the IV infusion line at the same infusion rate with 0.9% Sodium Chloride Injection to ensure all etranacogene dezaparvovec is delivered.[68294]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Etranacogene Dezaparvovec

      Revision Date: 09/29/2023, 01:50:00 AMCopyright 2004-2024 by Lawrence A. Trissel. All Rights Reserved.

      References

      68294 - Hemgenix (etranacogene dezaparvovec) suspension package insert. Kankakee, IL; CSL Behring LLC; 2022 Nov.

      Adverse Reactions

      Moderate

      • antibody formation
      • chest pain (unspecified)
      • elevated hepatic enzymes
      • infusion-related reactions
      • sinus tachycardia

      Mild

      • abdominal pain
      • chills
      • dizziness
      • fatigue
      • fever
      • flushing
      • headache
      • injection site reaction
      • malaise
      • nausea
      • pruritus

      Severe

      • anaphylactoid reactions
      • hepatotoxicity
      • new primary malignancy

      Infusion-related reactions, including hypersensitivity and anaphylaxis, occurred in 33% of subjects during clinical trials with etranacogene dezaparvovec. Closely monitor for signs and symptoms of an infusion-related reaction throughout the infusion period and for at least 3 hours after the end of the infusion. Do not infuse etranacogene dezaparvovec faster than 500 mL/hour. If an infusion-related reaction develops during administration, the infusion may be slowed or stopped. Restart infusion at a lower rate once the infusion reaction has resolved. Consider treatment with a corticosteroid or antihistamine for management of an infusion-related reaction. Infusion-related reaction symptoms occurred during infusion in 7 subjects and after infusion in 12 subjects. Symptoms resolved on the day or day 1 after infusion in 11 subjects and within 8 days after infusion in 8 subjects. Infusions were temporarily discontinued in 3 subjects and restarted at a slower infusion rate after treatment with antihistamines and/or corticosteroids. The infusion was stopped and not restarted in 1 subject. Symptoms may include chest tightness, headache (18%), abdominal pain (less than 5%), lightheadedness, flu-like symptoms (14%), shivering, flushing (less than 5%), rash, and hypertension. Dizziness occurred in 5% or more of subjects. Abdominal discomfort, chest discomfort [chest pain (unspecified)], chills, eye pruritus, fever, hives, injection site reaction, and sinus tachycardia occurred in less than 5% of subjects. Hypersensitivity or anaphylactoid reactions occurred in 2 subjects (4%). A subject experienced a hypersensitivity reaction at 12 minutes after initiation of administration of etranacogene dezaparvovec consisting of high blood pressure, red eyes, feeling warm, dizziness, coughing, dyspnea, elevated heart rate, shivering, and leg cramps. The infusion was stopped and not restarted; only 10% of the etranacogene dezaparvovec dose was administered. The patient recovered on the same day after treatment with intravenous diphenhydramine and intramuscular epinephrine. Another subject experienced a hypersensitivity reaction at 10 minutes after initiation of administration of etranacogene dezaparvovec consisting of itching, tightness of throat, and swelling of the right side of the neck. The dose was not interrupted and administered in full. All symptoms resolved on the same day without treatment.[68294]

      Intravenous administration of a liver-directed adeno-associated virus (AAV) vector could potentially lead to liver transaminase elevations (transaminitis). Transaminitis, particularly when observed in the first 3 months after etranacogene dezaparvovec administration, is presumed to occur due to immune-mediated injury of transduced hepatocytes (hepatotoxicity) and may reduce the therapeutic efficacy of the AAV-vector based gene therapy. Monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations weekly for 3 months after administration of etranacogene dezaparvovec. Continue to monitor transaminases in any person who develops elevated liver enzymes until liver enzymes return to baseline. If ALT increases to above the upper limit of normal or to twice the baseline value in the first 3 months post-dose, consider initiating a course of corticosteroids, along with factor IX activity monitoring: prednisone or prednisolone 60 mg/day PO for 1 week, 40 mg/day PO for 1 week, 30 mg/day PO for 2 weeks, 20 mg/day PO until ALT returns to baseline, then taper dosage by 5 mg/week to discontinue. The mean duration of corticosteroid use for elevated transaminases was 81.4 days (range, 51 to 130 days) in clinical trials. Medications equivalent to prednisone or prednisolone may also be used. A combined immunosuppressant regimen or the use of other products can be considered in case of prednisone or prednisolone treatment failure or contraindication. Elevated hepatic enzymes (i.e., ALT and AST) were reported in 42% of subjects in clinical trials. Most subjects had asymptomatic, mild elevations in transaminases. Elevated ALT concentrations occurred most often during the first 4 months after etranacogene dezaparvovec administrations. Some subjects had a late onset of elevated ALT concentrations between months 6 to 24; however all of these ALT values were less than 2 times the upper limit of normal (ULN) except for 1 subject. An additional 3 subjects had AST elevations between months 6 to 12. In a single subject, an ALT elevation more than 5 times the ULN occurred 24 days after etranacogene dezaparvovec administration and resolved by 51 days post-administration. There was a single subject who had an AST elevation more than 5 times the ULN that occurred 11 months post-administration and resolved to less than 2 times the ULN 8 days later. The majority of elevated ALT values returned to baseline; however, ALT values never resolved to normal at 2-year follow up in 9 subjects.[68294]

      After treatment with etranacogene dezaparvovec, all subjects experienced antibody formation of neutralizing anti-adeno-associated virus serotype 5 (AAV5) antibodies. In clinical studies, sustained humoral immune response to infused AAV5 capsid was observed in all subjects after treatment with etranacogene dezaparvovec. The neutralizing anti-AAV5 antibody concentrations raised above the upper limit of quantification by week 3 post-administration and remained elevated, as measured at month 24 post-dose. In a subject with a preexisting neutralizing anti-AAV5 antibody titer of 1:3,212, no human factor IX expression was observed, and restart of the exogenous factor IX prophylaxis was needed for bleeding events. Readministration of etranacogene dezaparvovec in the presence of high anti-AAV5 antibody titer has not been evaluated.[68294]

      Integration of liver-targeting adeno-associated viral (AAV) vector DNA into the genome may carry the theoretical risk of developing a new primary malignancy of hepatocellular carcinoma. In clinical trials, a single subject with preexisting risk factors for developing hepatic cancer developed a hepatocellular carcinoma, which was assessed as not likely related to etranacogene dezaparvovec treatment based on vector integration site analyses and whole genome sequencing. Etranacogene dezaparvovec-associated clonal expansion or carcinogenicity was not observed in clinical trials.[68294]

      Fatigue and malaise were reported in 12% of subjects given etranacogene dezaparvovec in clinical trials. Nausea was reported in 7% of subjects given etranacogene dezaparvovec in clinical trials.[68294]

      Revision Date: 09/29/2023, 01:50:00 AM

      References

      68294 - Hemgenix (etranacogene dezaparvovec) suspension package insert. Kankakee, IL; CSL Behring LLC; 2022 Nov.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • antibody formation
      • blood donation
      • breast-feeding
      • ethanol ingestion
      • factor IX inhibitors
      • geriatric
      • hepatic disease
      • hepatitis
      • laboratory test interference
      • new primary malignancy
      • pregnancy

      Preexisting neutralizing anti-adeno-associated viral vector (AAV) antibody formation may impede transgene expression at desired therapeutic concentrations in AAV-vector based gene therapies. A validated neutralizing anti-adeno-associated virus serotype 5 (AAV5) antibody assay is currently not available. In clinical trials with etranacogene dezaparvovec, an unvalidated clinical trial assay was utilized to assess preexisting neutralizing anti-AAV5 antibodies. The subgroup with detectable preexisting neutralizing anti-AAV5 antibodies up to titers of 1:678 had mean factor IX activity that was numerically lower compared to the subgroup without preexisting neutralizing anti-AAV5 antibodies. Subjects with and without preexisting neutralizing AAV5 antibodies demonstrated hemostatic protection. Persons who intend to receive treatment with etranacogene dezaparvovec are encouraged to enroll in a study to measure preexisting anti-AAV5 neutralizing antibodies by calling the manufacturer for etranacogene dezaparvovec. The study evaluates the effect of preexisting anti-AAV5 neutralizing antibodies on the risk of bleeding.[68294]

      Prior to administration of etranacogene dezaparvovec, perform liver health assessments, including enzyme testing [i.e., alanine aminotransferase (ALT), aspartate, aminotransferase (AST), alkaline phosphatase, and total bilirubin] and 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 etranacogene dezaparvovec. Integration of liver-targeting adeno-associated viral (AAV) vector DNA into the genome may carry the theoretical risk of developing a new primary malignancy of hepatocellular carcinoma. Persons with preexisting risk factors for hepatocellular carcinoma, such as advanced (geriatric) age and hepatic disease, including cirrhosis, advanced hepatic fibrosis, hepatitis B or C, non-alcoholic fatty liver disease (NAFLD), chronic ethanol ingestion, and non-alcoholic steatohepatitis (NASH), should receive abdominal ultrasound screenings and be monitored annually for alpha-fetoprotein (AFP) elevations in the 5 years after etranacogene dezaparvovec administration.[68294]

      Obtain factor IX inhibitor titer testing prior to administration of etranacogene dezaparvovec. In the event of a positive test result for human factor IX inhibitors, perform a retest within 2 weeks. If the initial factor IX inhibitor test and the retest are positive, do not administer etranacogene dezaparvovec. Also monitor for development of factor IX inhibitors after administration of etranacogene dezaparvovec. Perform an assay that detects factor IX inhibitors if bleeding is not controlled, or plasma factor IX activity concentrations decrease. When using an in vitro activated partial thromboplastin time (aPTT)-based one-stage clotting assay (OSA) for determining factor IX activity, plasma factor IX activity results can be affected by both the type of aPTT reagent and the reference standard used in the assay. This is important to consider particularly when changing the laboratory and/or reagents used in the assay. Therefore, the same assay and reagents are recommended to be used to monitor factor IX activity over time. The results of factor IX activity tests are lower if measured with chromogenic substrate assay (CSA) compared to OSA. Use of exogenous factor IX concentrates before and after etranacogene dezaparvovec may result in laboratory test interference and impede assessment of endogenous etranacogene dezaparvovec-derived factor IX activity.[68294]

      Advise patients to avoid cell, organ, tissue, and blood donation after receiving treatment with etranacogene dezaparvovec.[68294]

      There is no information on etranacogene dezaparvovec use during human pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. No adverse effects on mating rate, fertility indices, or fetal weights were observed in healthy mice given an intravenous predecessor of etranacogene dezaparvovec 6 days prior to mating. Vector DNA was not detected in the uterus, placenta, or fetus.[68294]

      There is no information on etranacogene dezaparvovec use during breast-feeding.[68294]

      Revision Date: 09/29/2023, 01:50:00 AM

      References

      68294 - Hemgenix (etranacogene dezaparvovec) suspension package insert. Kankakee, IL; CSL Behring LLC; 2022 Nov.

      Mechanism of Action

      Etranacogene dezaparvovec is an adeno-associated virus serotype 5 (AAV5) based gene therapy designed to deliver a copy of a gene encoding the Padua variant of human coagulation Factor IX (hFIX-Padua). A single infusion of etranacogene dezaparvovec results in cell transduction and an increase in circulating factor IX activity in persons with hemophilia B.[68294]

      Revision Date: 09/29/2023, 01:50:00 AM

      References

      68294 - Hemgenix (etranacogene dezaparvovec) suspension package insert. Kankakee, IL; CSL Behring LLC; 2022 Nov.

      Pharmacokinetics

      Route-Specific Pharmacokinetics

      Intravenous Route

      Subjects achieved mean uncontaminated (i.e., excluding measurements within 5 half-lives of factor IX replacement therapy) factor IX activity concentrations of 39%, 41.5%, 36.9%, and 36.7% of normal, at 6, 12, 18, and 24 months after etranacogene dezaparvovec administration, respectively. The time to onset of factor IX protein expression post-dose was detectable by first uncontaminated measurement at week 3. A total of 56% of subjects achieved absence of vector DNA from blood and 69% from semen by month 24 as confirmed by 3 subsequent measurements below limit of detection. Considering results obtained from 2 available consecutive samples below limit of detection, 74% and 87% of subjects were identified to have reached absence of vector DNA from blood and semen, respectively, at 24 months post-administration.[68294]

       

      Affected cytochrome P450 isoenzymes and drug transporters: none

      Special Populations

      Hepatic Impairment

      Factor IX activity was evaluated in subjects with varying degree of baseline liver pathology, specifically the degree of hepatic steatosis with the Controlled Attenuation Parameter (CAP) score. The mean uncontaminated factor IX activity for the subgroups with a CAP score of less than S2 (less than 260 decibels/m; range, 100 to 259) vs. a CAP score of S2 or more (260 decibels/m or more; range, 262 to 400) at 6, 12, 18, and 24 months after etranacogene dezaparvovec administration were 40.8 vs. 34.5, 46.4 vs. 32.6, 41.6 vs. 29.2, and 40.2 vs. 28.4, respectively.[68294]

      Renal Impairment

      Subjects with mild renal impairment (CrCl of 60 to 89 mL/minute) had approximately 37% higher factor IX activity compared to subjects with normal renal function (CrCl of 90 mL/minute or more) after administration of etranacogene dezaparvovec. A single subject with moderate renal impairment (CrCl of 30 to 59 mL/minute) had similar factor IX activity compared to subjects with normal renal function.[68294]

      Geriatric

      Limited data from subjects aged 60 to 75 years showed that the mean factor IX activity concentrations were approximately up to 2-fold higher compared to subjects aged 18 to 39 years, but comparable to subjects aged 40 to 59 years.[68294]

      Revision Date: 09/29/2023, 01:50:00 AM

      References

      68294 - Hemgenix (etranacogene dezaparvovec) suspension package insert. Kankakee, IL; CSL Behring LLC; 2022 Nov.

      Pregnancy/Breast-feeding

      pregnancy

      There is no information on etranacogene dezaparvovec use during human pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. No adverse effects on mating rate, fertility indices, or fetal weights were observed in healthy mice given an intravenous predecessor of etranacogene dezaparvovec 6 days prior to mating. Vector DNA was not detected in the uterus, placenta, or fetus.[68294]

      breast-feeding

      There is no information on etranacogene dezaparvovec use during breast-feeding.[68294]

      Revision Date: 09/29/2023, 01:50:00 AM

      References

      68294 - Hemgenix (etranacogene dezaparvovec) suspension package insert. Kankakee, IL; CSL Behring LLC; 2022 Nov.

      Interactions

      There are no drug interactions associated with Etranacogene Dezaparvovec products.
      Revision Date: 09/29/2023, 01:50:00 AM

      References

      Monitoring Parameters

      • clotting inhibitor titers
      • factor IX concentrations
      • LFTs

      US Drug Names

      • HEMGENIX
      ;