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FDA approves valoctocogene roxaparvovec gene therapy for adults with severe hemophilia A

On June 29, 2023, the FDA approved the use of valoctocogene roxaparvovec (AAV5-hFVIII-SQ), an adeno-associated virus serotype 5 (AAV5) vector-based gene therapy, for the treatment of adults with severe hemophilia A without pre-existing anti-AAV5 antibodies, detectable using the FDA-approved companion diagnostic test AAV5 DetectCDx. 1

Severe hemophilia A is a bleeding disorder characterized by extremely low levels of the blood clotting protein factor VIII (FVIII) due to a mutation in the gene producing FVIII.1 Valoctocogene roxaparvovec is a one-time gene therapy consisting of an AAV5 viral gene vector carrying a gene for human FVIII. This drives production of FVIII in the liver to increase blood levels of FVIII and ultimately reduce the risk of uncontrolled bleeding.1,2

The FDA approval is based on the results of the Phase III GENEr8-1 trial (NCT03370913), a multicenter study evaluating the efficacy and safety of valoctocogene roxaparvovec in men over 18 years old with severe hemophilia A who had previously been treated with prophylactic FVIII replacement therapy.1,3 This is the largest and longest global Phase III study to date for any gene therapy in hemophilia.3 The study reported a mean increase in FVIII activity levels of 41.9 UI/dL in weeks 49 through 52 following infusion.2 After at least three years following infusion, the mean annualized bleeding rate for a cohort of 112 decreased from 5.4 bleeds per year at baseline, to 2.6 bleeds per year.1 The three-year analysis also reported that 92% of patients remained off prophylaxis at the end of year three.3

Elevation in levels of the liver enzyme alanine aminotransferase was the most common adverse effect (seen in 85.5% of participants) but was managed using immunosuppressants.2 Close monitoring for infusion-related reactions and liver enzyme elevation is advised with valoctocogene roxaparvovec administration.1

Johannes Oldenburg, MD, University Clinic Bonn, Bonn, Germany, discussed AAV-based therapies in hemophilia in an interview at the 31st Congress of the International Society on Thrombosis and Haemostasis (ISTH), held in Montréal, Canada. Prof. Oldenburg comments on the benefits and challenges of these treatments which, he says, “will become a very promising option for the future.”

Valoctocogene roxaparvovec is the first gene therapy approved by the FDA for adults with severe hemophilia A and has the potential to transform the treatment of these patients.

References

  1. U.S. Food and Drug Administration. FDA Approves First Gene Therapy for Adults with Severe Hemophilia A. Available here (Accessed: 30/06/2023).
  2. Ozelo MC, Mahlangu J, Pasi KJ, et al. Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A. The New England Journal of Medicine. 2022 Mar 17; 386(11):1013-1025.
  3. BioMarin Announces Stable and Durable Annualized Bleed Control for ROCTAVIAN™ in Largest Phase 3 Gene Therapy Study in Adults with Severe Hemophilia A; 134-Participant Study Met All Primary and Secondary Efficacy Endpoints at 3-Year Analysis. Available here (Accessed: 30/06/2023).

Written by Louise Collinson
Edited by Elitsa Kamberska