In Brief | Blood Disorders | Haemophilia
Breakthrough in Haemophilia A: Gene Therapy Shows Lasting Benefits in Phase 3 Trial
Time to read: 04:56
Time to listen: 08:51
Originally Published: December 2024
Sourced: American Society of Haematology
Type of article: In Brief
MedED Catalogue Reference: MIBRD002
Category: Blood Disorders
Cross Reference: Haemophilia, Gene Therapy
Keywords: haemophilia, gene therapy, vector-therapy
The AFFINE study provides strong evidence that giroctocogene fitelparvovec could be a transformative one-time gene therapy for haemophilia A, significantly reducing bleeding rates and increasing FVIII activity, potentially improving patient quality of life.
This article is a review of the results of a clinical trial originally presented at the American Society of Haematology, December 2024. This article does not represent the original research, nor is it intended to replace the original research. Access the full Disclaimer Information.
Physicians may soon have a new tool for managing haemophilia A, as promising early results from an ongoing Phase 3 AFFINE study suggest that giroctocogene fitelparvovec, a one-time gene therapy, could become the second U.S. Food and Drug Administration (FDA)-approved gene therapy for this condition.
Giroctocogene fitelparvovec is a hepatocyte-directed recombinant adeno-associated virus serotype 6 (AAV6) vector, which encodes a B-domain-deleted variant of human factor VIII (FVIII).
The findings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting, indicate that the therapy has the potential to provide long-term bleeding control, reducing the need for ongoing FVIII replacement therapy.
If approved, giroctocogene fitelparvovec would follow efanesoctocog alfa, the first FDA-approved gene therapy for haemophilia A, which was authorized in 2023 for both paediatric and adult patient.
Editors Note
The term "hepatocyte-directed recombinant adeno-associated virus serotype 6 (AAV6) vector" describes a specialized gene therapy delivery system designed to target hepatocytes specifically. This vector is engineered for the efficient expression of therapeutic genes within the liver.
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Recombinant adeno-associated virus (AAV) vector: AAV is a non-pathogenic virus that has been genetically modified (recombinant) to prevent replication and disease transmission, ensuring safety during gene delivery. As a viral vector, it acts as a carrier for the gene of interest, facilitating its introduction into human cells.
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Serotype 6 (AAV6): AAV is classified into different serotypes, each with distinct characteristics. AAV6 is particularly effective at transducing hepatocytes, making it an optimal choice for liver-directed gene therapies, such as those aimed at treating haemophilia A by introducing a functional copy of the factor VIII gene.
In this context, AAV6 vectors offer a promising approach for gene therapies that require long-term expression of therapeutic proteins within the liver.
Study Purpose
Study Methodology
Secondary endpoints included FVIII activity levels, the number of treated bleeds, and safety assessments.
Findings
The trial met its primary endpoint, demonstrating a significant reduction in total ABR:
The AFFINE study offers compelling evidence that giroctocogene fitelparvovec could be a game-changing one-time gene therapy for haemophilia A. The findings highlight a significant reduction in bleeding rates and a lasting increase in FVIII activity, suggesting that gene therapy could really ease the treatment burden and enhance patients' quality of life.
Of course, individual responses can vary, so it's something to keep in mind, but the safety profile is looking positive overall. Most of the adverse events reported were short-term and manageable. That said, long-term follow-up is still crucial to better understand how durable the FVIII expression is and how it might fit into everyday clinical practice.
Conclusion
Importance of this study for South Africa
Gene therapy holds significant promise for South Africa, particularly in addressing conditions like haemophilia A.
Currently, of the 3,142 patients diagnosed with inherited clotting factor deficiencies in the country, 1,986 have haemophilia A. Traditional treatments, such as factor replacement therapy, are not only costly but also require regular administration, posing challenges in resource-limited settings.1,2
The high cost of these treatments often limits accessibility, leading to suboptimal care and increased morbidity. Introducing gene therapy could revolutionize haemophilia management by potentially offering a one-time treatment that provides long-term benefits, thereby reducing the ongoing financial burden on both patients and the healthcare system. 2
While gene therapy research in South Africa has been primarily limited to laboratory-based studies and preclinical trials, the establishment of haemophilia gene therapy programs as extensions of international trials marks a positive step forward. If the costs associated with gene therapy can be controlled, this approach could become a viable and sustainable solution, improving the quality of life for many South Africans living with haemophilia.3
Access the Original Trial
ClinicalTrials.gov Study to evaluate the efficacy and safety of PF-07055480 / Giroctocogene fitelparvovec gene therapy in moderately severe to severe haemophilia A adults (AFFINE)
Additional References
1. Mahlangu, J., Bassa, F., Bassingthwaighte, M., Cruickshank, A.-L., du Plessis, J., Goga, Y., Joubert, J., & Louw, V. (2022). Prophylaxis is the new standard of care in patients with haemophilia. South African Medical Journal, 112(6). https://hdl.handle.net/10520/ejc-m_samj_v112_n6_a7
2. Hendricks, C.L., Alessandrini, M. & Pepper, M.S. Equitable access to cell and gene therapies in South Africa: opportunities and hurdles. Gene Ther 30, 180–186 (2023). https://doi.org/10.1038/s41434-021-00309-y
3. Ely, A., Bloom, K., Maepa, M. B., Mahlangu, J. N., Pepper, M. S., & Arbuthnot, P. (2019). Gene and cell therapy in South Africa: Current status and future prospects. South African medical journal = Suid-Afrikaanse tydskrif vir
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