Male; ≥18 years of age; has congenital hemophilia B classified as moderately severe or severe (factor IX activity ≤2% of normal), and had both >150 previous exposure days to factor IX and received continuous prophylaxis for ≥2 months.
Factor IX inhibitors, active hepatitis B or hepatitis C infection, and/or uncontrolled HIV infection—as well as evidence of advanced liver disease.
* The full analysis set (FAS) included 1 patient who died at month 15 post-dose due to unrelated concomitant disease.
HEMGENIX is a suspension for intravenous infusion after dilution. It is provided in kits containing 10-48 vials; each kit is ordered based on the patient’s body weight. HEMGENIX has a nominal concentration of 1 x 1013 genome copies (gc)/mL, and each vial contains an extractable volume of not less than 10 mL. The recommended dose of HEMGENIX is 2 x 1013 gc per kg of body weight (or 2 mL per kg body weight) administered as an intravenous infusion after dilution with 0.9% normal saline.
*Further dilution with 0.9% normal saline is required.
References: 1. Miesbach W, Frank WG, Leebeek FWG, Recht M, et al; for the HOPE-B Investigators. Final analysis from the pivotal phase 3 HOPE-B gene therapy trial: stable steady-state efficacy and safety of etranacogene dezaparvovec in adults with severe or moderately severe haemophilia B. Presented at: 15th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD 2022); February 2-4, 2022; Virtual. 2. Pipe S, Leebeek FWG, Ferreira V, Sawyer EK, Pasi J. Clinical considerations for capsid choice in the development of liver-targeted AAV-based gene transfer. Mol Ther Methods Clin Dev. 2019;15:170-178. doi:10.1016/j.omtm.2019.08.015 3. Vance MA, Mitchell A, Samulski RJ. AAV biology, infectivity and therapeutic use from bench to clinic. In: Hashad D, ed. Gene Therapy: Principles and Challenges [Internet]. IntechOpen; 2015. Accessed October 13, 2022. doi: 10.5772/61988 4. Perrin GQ, Herzog RW, Markusic DM. Update on clinical gene therapy for hemophilia. Blood. 2019;133(5):407-414. doi:10.1182/blood-2018-07-820720 5. Bulcha JT, Wang Y, Ma H, Tai PWL, Gao G. Viral vector platforms within the gene therapy landscape. Signal Transduct Target Ther. 2021 Feb 8;6(1):53. doi:10.1038/s41392-021-00487-6 6. Arruda VR, Doshi BS. Gene therapy for hemophilia: facts and quandaries in the 21st century. Mediterr J Hematol Infect Dis. 2020;12(1):e2020069. doi:10.4084/MJHID.2020.069
Warning and Precautions
Infusion reactions, including hypersensitivity reactions and anaphylaxis, may occur. Monitor during administration and for at least 3 hours after end of infusion. If symptoms occur, slow or interrupt administration. Re-start administration at a slower infusion once resolved.
Post-dose, monitor for elevated transaminase levels. Consider corticosteroid treatment should elevations occur. The integration of liver-targeting AAV vector DNA into the genome may carry the theoretical risk of hepatocellular carcinoma development. For patients with preexisting risk factors for hepatocellular carcinogenicity, perform regular (eg, annual) abdominal ultrasound and alpha-fetoprotein testing following administration.
Immune-mediated neutralization of the AAV5 vector capsid
Preexisting neutralizing anti-AAV antibodies may impede transgene expression at desired levels.
Monitoring Laboratory Tests
In addition to monitoring liver function, monitor for Factor IX activity and Factor IX inhibitors after administration.
The most common adverse reactions (incidence ≥5%) were elevated ALT, headache, blood creatine kinase elevations, flu-like symptoms, infusion-related reactions, fatigue, nausea, malaise, and elevated AST.
HEMGENIX®, etranacogene dezaparvovec-drlb, is an adeno-associated virus vector-based gene therapy indicated for the treatment of adults with Hemophilia B (congenital Factor IX deficiency) who:
HEMGENIX is for single use intravenous infusion only.
Please see full prescribing information for HEMGENIX.
To report SUSPECTED ADVERSE REACTIONS, contact the CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.