Written by Aishwarya Shinde (B.Pharm)
Reviewed and Fact Checked by Vikas Londhe M.Pharm (Pharmacology)
The U.S. Food and Drug Administration (FDA) has granted approval for Qfitlia (fitusiran), a groundbreaking therapy designed for the routine prophylaxis of bleeding episodes in individuals with haemophilia A or B. This approval, announced on March 28, 2025, marks a significant advancement in the treatment of these rare genetic bleeding disorders. Qfitlia is authorized for use in adults and pediatric patients aged 12 years and older, regardless of the presence of factor VIII or IX inhibitors.
Haemophilia A and B
Haemophilia is a rare, inherited bleeding disorder caused by deficiencies in clotting factors, leading to prolonged bleeding episodes. The two main types are Haemophilia A (deficiency of Factor VIII) and Haemophilia B (deficiency of Factor IX), both inherited as X-linked recessive disorders. Since the defective gene is located on the X chromosome, males (XY) are typically affected, while females (XX) are usually carriers. However, rare cases of female haemophilia can occur due to lyonization, where the healthy X chromosome is inactivated.
Conventional treatments for haemophilia focus on managing bleeding episodes and preventing complications. Replacement therapy includes recombinant or plasma-derived Factor VIII concentrates for Haemophilia A and Factor IX concentrates for Haemophilia B. Prophylactic treatment involves regular infusions to prevent bleeding, particularly in severe cases. Additional therapies include Desmopressin (DDAVP) for mild Haemophilia A, which stimulates Factor VIII release, and antifibrinolytics like tranexamic acid to stabilize clots, especially in mucosal bleeding.
Recent advances in treatment include gene therapy, such as etranacogene dezaparvovec for Haemophilia B, offering potential long-term solutions. Haemophilia A is more prevalent, affecting approximately 1 in 5,000 male births, while Haemophilia B occurs in 1 in 30,000 male births. Globally, an estimated 400,000 people are affected by the disorder. Ongoing research and novel therapies aim to improve quality of life and reduce the burden of this chronic condition.
Need of an Advance Therapy
However the advanced therapies are needed for haemophilia A and B to address the limitations of conventional treatments and improve patient outcomes. While traditional factor replacement therapies are effective, they require frequent intravenous infusions, which can be burdensome for patients and may lead to complications like inhibitor development (antibodies against clotting factors). Additionally, some patients experience breakthrough bleeding despite prophylaxis, highlighting the need for more durable and convenient solutions.
Qfitlia: A Novel Approach to Haemophilia Management
Developed by Sanofi, Qfitlia (Fitusiran) is an RNA interference (RNAi) therapeutic developed for the treatment of haemophilia A and B, as well as other bleeding disorders. It is designed to reduce bleeding episodes by silencing the production of antithrombin (AT), a natural anticoagulant protein, through RNA interference rather than replacing the missing clotting factors (as in conventional therapies).
Fitusiran is a synthetic siRNA molecule encapsulated in a lipid nanoparticle for targeted delivery to hepatocytes (liver cells). Once inside the liver, it binds to the messenger RNA (mRNA) encoding antithrombin (SERPINC1 gene).
The siRNA triggers the degradation of antithrombin mRNA, reducing antithrombin production. Lower antithrombin levels shift the hemostatic balance toward a pro-coagulant state, promoting thrombin generation and improving clot formation.
In haemophilia, deficient Factor VIII (Haemophilia A) or Factor IX (Haemophilia B) leads to impaired thrombin burst, by reducing antithrombin, fitusiran bypasses the need for exogenous clotting factors, allowing even low levels of endogenous Factors VIII/IX to work more effectively.
The therapy is administered via subcutaneous injections as few as six times per year, offering a significant reduction in treatment burden compared to existing options. It is available in a convenient prefilled pen or vial-and-syringe format, making it easier for patients and caregivers to manage.
Clinical Efficacy
The FDA’s approval was based on data from Sanofi’s ATLAS clinical trial program, which included phase 3 studies such as ATLAS-A/B and ATLAS-INH.
ATLAS-A/B study was a Phase 3, multicenter, open-label, randomized trial evaluating the efficacy and safety of fitusiran prophylaxis in males aged 12 years and older with severe haemophilia A or B without inhibitors. The study enrolled 120 participants across 45 sites in 17 countries.Participants were randomized in a 2:1 ratio to receive either once-monthly 80 mg subcutaneous fitusiran prophylaxis or continue with on-demand clotting factor concentrates for duration of 9 months.
Key Findings includes, Annualized Bleeding Rate (ABR): The median ABR was 0.0 (interquartile range [IQR] 0.0–3.4) in the fitusiran group, compared to 21.8 (IQR 8.4-41.0) in the on-demand group. The estimated mean ABR was significantly lower in the fitusiran group (3.1) than in the on-demand group (31.0), representing an approximate 90% reduction. Bleed-Free Participants: Approximately 51% of participants in the fitusiran group experienced no treated bleeds during the study period, compared to 5% in the on-demand group.
ATLAS-INH study, was a Phase 3, open-label, randomized trial evaluating the efficacy and safety of fitusiran in individuals aged 12 years and older with severe haemophilia A or B who have inhibitors to factor VIII or IX. Participants were randomly assigned in a 2:1 ratio to receive once-monthly 80 mg subcutaneous fitusiran prophylaxis or to continue with on-demand treatment using bypassing agents (BPAs).
Fitusiran prophylaxis led to a significant reduction in the annualized bleeding rate (ABR), with a 90.8% decrease compared to the on-demand BPA group. Approximately 66% of participants receiving fitusiran experienced zero treated bleeds during the study period, compared to 5% in the BPA group.
Based on the results from the ATLAS-INH and other related trials, the U.S. Food and Drug Administration (FDA) approved fitusiran, marketed as Qfitlia, for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients aged 12 years and older with haemophilia A or B, with or without inhibitors.
Safety Profile
The safety profile of Qfitlia includes warning for serious thrombotic event and acute and recurrent gall bladder disease. The most common treatment-emergent adverse event in the fitusiran group was increased alanine aminotransferase levels, observed in 32% of participants.
Benefits for Patients
Qfitlia represents a paradigm shift in haemophilia care by combining effective bleed protection with infrequent dosing and simplified administration. “This approval highlights our commitment to advancing innovation and improving care for the rare blood disorders community,” said Brian Foard, executive vice president at Sanofi Tanya Wroblewski, MD, deputy director at the FDA’s Center for Drug Evaluation and Research, emphasized that this therapy “can be administered less frequently than other existing options,” improving quality of life for patients.
Conclusion
The FDA’s approval of Qfitlia marks a transformative moment for individuals living with haemophilia A or B. By offering effective bleed prevention with minimal treatment burden, this innovative therapy has the potential to significantly improve patient outcomes and redefine standards of care worldwide.
References
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