The American Society of Hematology (ASH) Annual Meeting 2024 showcased substantial advancements in hemophilia treatment, spanning prophylactic, curative, and on-demand care approaches. Physicians reflected on the transformative impact of Roche's Hemlibra (emicizumab) and the recent approvals of adeno-associated virus (AAV) gene therapies, including CSL Behring’s Hemgenix (etranacogene dezaparvovec) for hemophilia B, BioMarin’s Roctavian (valoctocogene roxaparvovec) for hemophilia A, and Pfizer’s Beqvez (fidanacogene elaparvovec) for hemophilia B. Pfizer's Hympavzi (marstacimab), a weekly subcutaneous injection, also received FDA approval in 2024 for both hemophilia A and B without inhibitors. However, significant unmet needs remain, including breakthrough bleeds, access limitations, and long-term safety concerns.
Unmet Needs and Emerging Therapies
Despite the availability of new therapies, many hemophilia patients on regular prophylaxis still experience spontaneous bleeding episodes, and the frequent injections contribute to a high disease burden. Access to gene therapies is limited, as highlighted at ASH 2024, where few physicians had prescribed gene therapy products commercially, despite using them in clinical trials. Concerns persist regarding the long-term risks of gene therapies, particularly hepatocellular carcinoma and the effects of prolonged corticosteroid use to manage liver toxicity.
Pfizer presented Phase III results from the AFFINE trial of its gene therapy, giroctocogene fitelparvovec, in moderately severe to severe hemophilia A patients without inhibitors. Two years post-dosing, approximately 10% of patients had factor VIII levels below 1%, necessitating a return to prophylaxis. While this efficacy data mirrors that of Roctavian, giroctocogene fitelparvovec demonstrated a better safety profile, with 62.7% of patients experiencing elevated alanine aminotransferase (ALT) levels compared to 85.8% for Roctavian. GlobalData anticipates FDA approval for giroctocogene fitelparvovec in 2025.
Prophylaxis and On-Demand Treatment Options
Sanofi presented results from its Phase III open-label expansion trial for fitusiran, a small-interfering RNA (siRNA) therapy in pre-registration for hemophilia A and B with or without inhibitors. Fitusiran significantly reduced annual bleeds compared to bypassing agents and delivered efficacy similar to clotting factor replacement therapy. While older prophylaxis treatments require multiple intravenous infusions per week, fitusiran, administered via weekly subcutaneous injections, will likely be compared to monoclonal antibodies like Hympavzi and Hemlibra, or Sanofi’s Altuviio (efanesoctocog alfa). Hemlibra's monthly subcutaneous injections may allow it to maintain a high market share.
For price-sensitive markets and patients with mild hemophilia, on-demand treatment options remain crucial. Staidson presented data on its novel fusion protein, bemiltenase alfa, which activates factor X and functions in both hemophilia A and B with or without inhibitors. Bemiltenase alfa achieved an 83% 12-hour bleed clearance rate, compared to 60% for Novo Nordisk’s NovoSeven (inneptacog alfa). Staidson has completed a Phase II pivotal trial in China and received FDA Investigational New Drug (IND) clearance to expand into the US.
The Future of Hemophilia Treatment
Significant advancements are being made across curative, prophylactic, and on-demand hemophilia treatment categories. Novel modalities and mechanisms of action are expanding treatment options, addressing unmet patient needs. While curative therapies offer the promise of a hemophilia-free life, current options for hemophilia A may not provide lifelong cures, potentially requiring a return to prophylaxis or on-demand treatment. Access to advanced therapies remains a major challenge, sustaining a significant market for prophylaxis and on-demand treatments.
