HEMGENIX AAV5 GENE THERAPY
Specifically designed to target hemophilia B
HEMGENIX is a gene therapy that uses an in vivo method of gene transfer, introducing a functional copy of the F9 gene to compensate for the F9 mutation. See how it works:
What does HEMGENIX consist of?
Liver-directed AAV5 vector
This nonreplicating, nonpathogenic AAV5 (adeno-associated viral vector serotype 5)
was chosen because there is a lower prevalence of preexisting immunity (neutralizing
antibodies or NAbs) to it in the general population.
AAV5 targets liver cells,* and also has a serotype-specific tropism for hepatocytes,
which are an ideal target for transduction since they are where factor IX is normally
*Based on animal studies.
Highly active factor IX-Padua gene variant
Factor IX-Padua has been shown to generate 5 to 8 times higher mean endogenous factor IX activity than the more common wild-type gene. The factor IX-Padua gene is under the control of a liver-specific promoter.7,8
With HEMGENIX, the factor IX-Padua gene is contained within an AAV5 vector to introduce a functional copy of the F9 gene into a patient’s hepatocytes.
References: 1. Zincarelli C, Soltys S, Rengo G, Rabinowitz JE. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol Ther. 2008;16(6):1073-1080. doi:10.1038/mt.2008.76 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. Louis Jeune V, Joergensen JA, Hajjar RJ, Weber T. Pre-existing anti–adeno-associated virus antibodies as a challenge in AAV gene therapy. Hum Gene Ther Methods. 2013;24(2):59-67. doi:10.1089/hgtb.2012.243 4. 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 5. Ronzitti G, Gross DA, Mingozzi F. Human immune responses to adeno-associated virus (AAV) vectors. Front Immunol. 2020;11:670. Published April 17, 2020. doi:10.3389/fimmu.2020.00670 6. 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 7. Simioni P, Tormene D, Tognin G, et al. X-linked thrombophilia with a mutant factor IX (factor IX Padua). N Engl J Med. 2009;361(17):1671-1675. doi:10.1056/NEJMoa0904377 8. Nathwani AC. Gene therapy for hemophilia. Hematology Am Soc Hematol Educ Program. 2019;2019(1):1-8. doi:10.1182/hematology.2019000007
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.