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Fidanacogene Elaparvovec: First Approval

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Abstract

Fidanacogene elaparvovec (PrBEQVEZ™) is an adeno-associated viral (AAV) vector-based gene therapy developed by Spark Therapeutics (a subsidiary of Roche) and Pfizer (under a license from Spark Therapeutics) for the treatment of haemophilia B. In December 2023, fidanacogene elaparvovec received its first approval for the treatment of adults (aged ≥ 18 years) with moderately severe to severe haemophilia B (congenital factor IX deficiency) who are negative for neutralizing antibodies to variant AAV serotype Rh74 (AAVRh74var). Fidanacogene elaparvovec is under regulatory review in the USA and the European Union and clinical studies are ongoing in multiple countries. This article summarizes the milestones in the development of fidanacogene elaparvovec leading to this first approval for moderately severe to severe (factor IX activity ≤ 2%) haemophilia B who are negative for neutralizing antibodies to AAVRh74var.

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References

  1. Miller CH. The clinical genetics of hemophilia B (factor IX deficiency). Appl Clin Genet. 2021;14:445–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Samelson-Jones BJ, George LA. Adeno-associated virus gene therapy for hemophilia. Annu Rev Med. 2023;74:231–47.

    Article  CAS  PubMed  Google Scholar 

  3. Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020;26(Suppl 6):1–158.

    Article  PubMed  Google Scholar 

  4. George LA, Sullivan SK, Giermasz A, et al. Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med. 2017;377(23):2215–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Manno CS, Pierce GF, Arruda VR, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med. 2006;12(3):342–7.

    Article  CAS  PubMed  Google Scholar 

  6. Monahan P, Walsh C, Powell J, et al. Update on a phase 1/2 open-label trial of BAX335, an adeno-associated virus 8 (AAV8) vector-based gene therapy program for hemophilia B [abstract no. LB010]. J Thromb Haemost. 2015;13(Suppl 2):010.

    Google Scholar 

  7. Nathwani AC, Reiss UM, Tuddenham EG, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014;371(21):1994–2004.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Crudele JM, Finn JD, Siner JI, et al. AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice. Blood. 2015;125(10):1553–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pfizer Canada ULC. PrBEQVEZTM (fidanacogene elaparvovec): Canadian prescribing information 2023. https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=103268. Accessed 8 Jan 2024.

  10. Spark Therapeutics. Spark Therapeutics Launched with $50 Million in Financing to Advance Late- and Mid-Stage Gene Therapy Programs with Clinical Proof of Concept [media release]. https://www.prnewswire.com/news-releases/spark-therapeutics-launched-with-50-million-in-financing-to-advance-late--and-mid-stage-gene-therapy-programs-with-clinical-proof-of-concept-228752221.html. Accessed 22 Oct 2013.

  11. Spark Therapeutics. Amedment to form S-1. 2015. https://www.sec.gov/Archives/edgar/data/1609351/000119312515013888/d776249ds1a.htm. Accessed 28 Jan 2024.

  12. Pfizer. Spark Therapeutics and Pfizer announce that SPK-9001, an investigational hemophilia B Medicine, has been granted access to the PRIority MEdicines (PRIME) program by the European Medicines Agency [media release]. https://sparktx.com/press_releases/spark-therapeutics-and-pfizer-amend-license-agreement-for-investigational-spk-9001-in-hemophilia-b/. Accessed 1 Mar 2017.

  13. Spark Therapeutics. Spark Therapeutics reports 2017 financial results and recent business progress. 2018. https://sparktx.com/press_releases/spark-therapeutics-reports-2017-financial-results-and-recent-business-progress/. Accessed 28 Jan 2024.

  14. Roche. Roche concludes acquisition of Spark Therapeutics, Inc. to strengthen presence in gene therapy [media release]. https://www.roche.com/media/releases/med-cor-2019-12-17b. Accessed 17 Dec 2019.

  15. George LA, Sullivan SK, Rasko JEJ, et al. Efficacy and safety in 15 hemophilia B patients treated with the AAV gene therapy vector fidanacogene elaparvovec and followed for at least 1 year [abstract no. 3347]. Blood. 2019;134(Suppl 1):3347.

    Article  Google Scholar 

  16. Frenzel L, Alzahrani H, Cuker A, et al. Vector clearance following administration of fidanacogene elaparvovec gene therapy in adults with haemophilia B [abstract no. PO132]. Haemophilia. 2024;30(Suppl 1):124–5.

    Google Scholar 

  17. Cuker A, Alzahrani H, Astermark J, et al. Efficacy and safety of fidanacogene elaparvovec in adults with moderately severe or svere hemophilia B: results from the phase 3 BENEGENE-2 gene therapy trial [abstract no. OC 52.3]. Res Pract Thromb Haemost. 2023;7(Suppl 2):124–5.

    Google Scholar 

  18. Frenzel L, Kavakli K, Klamroth R, et al. Characterizing a cohort of patients with hemophilia B treated with fidanacogene elaparvovec from the phase 3 BENEGENE-2 study who returned to factor IX prophylaxis. Blood. 2023;142(Suppl 1):2257.

    Article  Google Scholar 

  19. von Mackensen S, Bagot CN, Lienhart A, et al. Health-related quality of life in adults with haemophilia B after gene therapy with fidanacogene elaparvovec in the BENEGENE-2 trial [abstract no. PO116]. Haemophilia. 2024;30(Suppl 1):92.

    Google Scholar 

  20. Rasko JEJ, Chhabra A, Ducore JM, et al. Patterns of joint bleeds in patients with hemophilia B following fidanacogene elaparvovec adeno-associated virus gene therapy. Haemophilia. 2023;29(Suppl 1):113–4.

    Google Scholar 

  21. Samelson-Jones BJ, Sullivan SK, Rasko JEJ, et al. Follow-up of more than 5 years in a cohort of patients with hemophilia B treated with fidanacogene elaparvovec adeno-associated virus gene therapy. Blood. 2021;138(Suppl 1):3975.

    Article  Google Scholar 

  22. von Mackensen S, Ducore JM, George LA, et al. Health-related quality of life in adults with hemophilia B after receiving gene therapy with fidanacogene elaparvovec. Blood. 2023;142(Suppl 1):3628.

    Article  Google Scholar 

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    Sohita Dhillon

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  1. Sohita Dhillon
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Correspondence to Sohita Dhillon.

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The preparation of this review was not supported by any external funding.

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During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Sohita Dhillon is a contracted employee of Adis International Ltd/Springer Nature and declares no relevant conflicts of interest. All authors contributed to this article and are responsible for its content.

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This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

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Dhillon, S. Fidanacogene Elaparvovec: First Approval. Drugs 84, 479–486 (2024). https://doi.org/10.1007/s40265-024-02017-4

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