At the turn of the 21st century, there was great excitement and anticipation of gene therapy as a ‘curative’ treatment for hemophilia A and B patients, particularly among those with moderate-to-severe forms of the disease. However, a recent forum piece in the journal Research & Practice in Thrombosis & Haemostasis (RPTH) offers some reasons why the overall commercial uptake of these therapies has been relatively modest, as lingering questions over long-term efficacy (in the case of hemophilia A) and longer-term safety of these first-generation gene therapies. In addition, matters of high cost and delivery infrastructure continue to present major access hurdles for the global hemophilia community.
In late 2024, Pfizer opted to not submit a biological license application for their investigational hemophilia A gene therapy (giroctocogene fitelparvovec) and ceased commercialization of their recently approved hemophilia IX product fidanacogene elaparvovec in February 2025. In Pfizer communications announcing the discontinuation, the onus was put on the hemophilia community citing the “weak demand” from patients and their physicians. The authors pushed back strongly on an industry narrative that might suggest that the slow uptake of gene therapy is indicative of low interest in these curative therapies and necessitated the pullback.
Rather, the authors argue, industry needs to be more focused on developing gene therapies that offer distinct therapeutic benefits over existing novel nonfactor therapies and more favorable risk/benefit ratios especially considering the “one-and-done” nature of currently FDA approved AAV-vectors based therapies.
The paper outlines the many variabilities relevant to overall therapeutic response (e.g. suboptimal vs curative effect) and the presence and management of elevated liver enzymes (transaminitis). The authors also lay out the intrinsic (e.g. durability, side effects), extrinsic (e.g. high cost, reimbursement), and patient decision-making variables (e.g. availability of effective less burdensome non-factor therapies), all of which affect the adoption of gene therapy. Key differences between hemophilia A and hemophilia B therapies, the latter of which has shown better long-term durability, are also described.
“People with hemophilia in countries of all income levels desire to be cured. While the balance between benefits and risks depends on locally available therapies, moving in the direction of zero bleeds and a ‘hemophilia-free mind’ remains the goal,” concluded the authors. “The community looks forward to seeing new technologies exploited to improve the increasingly imbalanced global health equity and provide a functional cure for all people with hemophilia.”
“Why is the Uptake of Gene Therapy in Hemophilia Less than Expected?” was published in RPTH on June 23, 2025. Read the full open access piece here.
Citation
Pierce GF, Skinner M, O’Mahony B, Rotellini D, Kaczmarek R. Why is the Uptake of Gene Therapy in Hemophilia Less Than Expected? Research and Practice in Thrombosis and Haemostasis, Volume 9, Issue 5, 102948, July 28, 2025.
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