Valoctocogene Roxaparvovec: First Approval

Overview

Journal Drugs

Specialty Pharmacology

Date 2022 Oct 10

PMID 36214970

Authors

Hannah A Blair

Affiliations

Soon will be listed here.

Abstract

Valoctocogene roxaparvovec (ROCTAVIAN) is a gene therapy being developed by BioMarin Pharmaceutical Inc. for the treatment of haemophilia A. In August 2022, valoctocogene roxaparvovec was granted conditional marketing authorization in the EU for the treatment of severe haemophilia A [congenital factor VIII (FVIII) deficiency] in adults without a history of FVIII inhibitors and without detectable antibodies to adeno-associated virus serotype 5 (AAV5). This article summarizes the milestones in the development of valoctocogene roxaparvovec leading to this first approval for severe haemophilia A.

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References

Fassel H, McGuinn C . Haemophilia: factoring in new therapies. Br J Haematol. 2021; 194(5):835-850. DOI: 10.1111/bjh.17580. View

Bunting S, Zhang L, Xie L, Bullens S, Mahimkar R, Fong S . Gene Therapy with BMN 270 Results in Therapeutic Levels of FVIII in Mice and Primates and Normalization of Bleeding in Hemophilic Mice. Mol Ther. 2018; 26(2):496-509. PMC: 5835117. DOI: 10.1016/j.ymthe.2017.12.009. View

Sihn C, Handyside B, Liu S, Zhang L, Murphy R, Yates B . Molecular analysis of AAV5-hFVIII-SQ vector-genome-processing kinetics in transduced mouse and nonhuman primate livers. Mol Ther Methods Clin Dev. 2022; 24:142-153. PMC: 8749450. DOI: 10.1016/j.omtm.2021.12.004. View

Long B, Sandza K, Holcomb J, Crockett L, Hayes G, Arens J . The Impact of Pre-existing Immunity on the Non-clinical Pharmacodynamics of AAV5-Based Gene Therapy. Mol Ther Methods Clin Dev. 2019; 13:440-452. PMC: 6513774. DOI: 10.1016/j.omtm.2019.03.006. View

Fonck C, Su C, Arens J, Koziol E, Srimani J, Henshaw J . Lack of germline transmission in male mice following a single intravenous administration of AAV5-hFVIII-SQ gene therapy. Gene Ther. 2022; 30(7-8):581-586. PMC: 10457182. DOI: 10.1038/s41434-022-00318-5. View

Zhang L, Handyside B, Murphy R, Sihn C, Xie L, Vitelli C . Prednisolone Does Not Regulate Factor VIII Expression in Mice Receiving AAV5-hFVIII-SQ: Valoctocogene Roxaparvovec. Mol Ther Methods Clin Dev. 2020; 17:13-20. PMC: 6923509. DOI: 10.1016/j.omtm.2019.11.007. View

Ozelo M, Mahlangu J, Pasi K, Giermasz A, Leavitt A, Laffan M . Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A. N Engl J Med. 2022; 386(11):1013-1025. DOI: 10.1056/NEJMoa2113708. View

Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M . AAV5-Factor VIII Gene Transfer in Severe Hemophilia A. N Engl J Med. 2017; 377(26):2519-2530. DOI: 10.1056/NEJMoa1708483. View

Pasi K, Rangarajan S, Mitchell N, Lester W, Symington E, Madan B . Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A. N Engl J Med. 2020; 382(1):29-40. DOI: 10.1056/NEJMoa1908490. View

10.

Pasi K, Laffan M, Rangarajan S, Robinson T, Mitchell N, Lester W . Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. Haemophilia. 2021; 27(6):947-956. PMC: 9291073. DOI: 10.1111/hae.14391. View

11.

Long B, Veron P, Kuranda K, Hardet R, Mitchell N, Hayes G . Early Phase Clinical Immunogenicity of Valoctocogene Roxaparvovec, an AAV5-Mediated Gene Therapy for Hemophilia A. Mol Ther. 2020; 29(2):597-610. PMC: 7854299. DOI: 10.1016/j.ymthe.2020.12.008. View