Drug Update · Hematology

FDA Approves Fitusiran for Hemophilia A/B: Median Treated ABR 3.7

July 11, 2026

Approval date

2025-03-28

Indication

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients aged 12 years and older with hemophilia A or B with or without factor VIII or IX inhibitors

Median treated ABR

3.7 (IQR 0.0; 7.5) [ATLAS-OLE]

Starting dose (approved)

50 mg once every 2 months

AT activity target

Maintain antithrombin activity 15–35%

Clinical Perspective

This approval affects hematology clinicians prescribing prophylaxis for adults and adolescents (≥12 years) with hemophilia A or B with or without factor VIII/IX inhibitors; the FDA label specifies QFITLIA for routine prophylaxis to prevent or reduce bleeding episodes ^[5]^[4]. The approved dosing strategy starts at 50 mg once every 2 months with antithrombin monitoring and individualized dose/frequency adjustments to maintain AT activity 15–35%, and clinicians must follow AT-guided dosing and monitoring schedules described in the label ^[5]^[4]. Because of specific safety risks observed in trials — thrombotic events, gallbladder disease, and liver enzyme elevations — clinicians will need to follow the label guidance on baseline and on-treatment testing and interrupt therapy for thrombotic events or significant hepatobiliary disease ^[4]^[5].

Dr. Shruti Pandey · Hematology

The FDA approved QFITLIA (fitusiran) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients aged 12 years and older with hemophilia A or B with or without factor VIII or IX inhibitors on 2025-03-28 based on data from the ATLAS program showing a median observed annualized bleeding rate for treated bleeds of 3.7 (IQR 0.0; 7.5) in the ATLAS-OLE analysis ^[5]. The approved starting regimen is 50 mg once every 2 months with antithrombin-directed dose adjustment to target antithrombin activity 15–35% ^[5]^[4]. Clinicians should consult current prescribing information for full dosing guidance.

Clinical Context

Fitusiran (QFITLIA) is a double-stranded small interfering RNA (siRNA) that reduces antithrombin (AT) messenger RNA, lowering plasma AT levels to enhance thrombin generation and reduce bleeding risk in people with congenital hemophilia A or B ^[5]. The agent is developed and marketed by Genzyme Corporation (a Sanofi company) and is supplied as a 50 mg prefilled pen and a 20 mg vial for subcutaneous administration ^[3]^[4]^[2]. Clinicians should consult current prescribing information for full dosing guidance. Regulatory reviews and labeling implement an antithrombin-directed dosing regimen (AT-DR) that uses serial AT measurements and dose adjustments to maintain AT activity between 15–35% after initiation, with a recommended starting dose of 50 mg once every 2 months ^[5]^[4]. Non-clotting factor prophylactic strategies such as emicizumab and fitusiran have been evaluated against on-demand therapy in randomized trials and systematic reviews comparing effects on annualized bleeding rates and the proportion of participants with zero bleeds ^[1]^[5].

Key Findings

In the long-term extension study ATLAS-OLE using an antithrombin-based dosing regimen, the median observed annualized bleeding rate (ABR) for treated bleeds was 3.7 (IQR 0.0; 7.5) in patients treated with fitusiran (AT-DR: starting dose 50 mg every two months with AT-guided adjustments) ^[5].
Clinicians should consult current prescribing information for full dosing guidance.
In the randomized trials and pooled program that supported regulatory review, ATLAS-INH randomized 57 participants with inhibitors (2:1 fitusiran 80 mg monthly vs on-demand BPA) and ATLAS A/B randomized 120 participants without inhibitors (2:1 fitusiran 80 mg monthly vs on-demand CFC), with subsequent transition of participants into ATLAS-OLE and implementation of the AT-DR after thrombotic signals with fixed dosing were identified ^[5]^[4].
A Cochrane systematic review of randomized controlled trials reported that fitusiran likely reduced annualized bleeding rates for all bleeds versus on-demand therapy with a mean difference of -28.80 (95% CI -40.07 to -17.53) in one trial of 57 participants with inhibitors, and reported a 12.5-fold increase in the proportion of participants with no bleeds for fitusiran versus on-demand therapy in included studies ^[1]. These comparative estimates come from RCT data synthesized in the Cochrane review rather than single-arm medians ^[1].

Safety & Tolerability

Thrombotic events: Serious thrombotic events have occurred in QFITLIA-treated patients; risk factors included persistent AT activity <15%, fixed 80 mg once-monthly dosing, indwelling venous catheters, and post-operative settings when bleed-management guidance was not followed; monitoring and interruption are recommended for thrombotic events ^[4]^[5].
Clinicians should consult current prescribing information for full dosing guidance.
Acute and recurrent gallbladder disease: Gallbladder events including cholelithiasis and cholecystitis occurred in clinical studies; in fixed-dose cohorts 17% experienced gallbladder events and 4% underwent cholecystectomy, while lower rates were observed with the AT-DR (3.8% gallbladder events; 0.3% cholecystectomy) ^[4].
Hepatotoxicity: Elevations of alanine and aspartate transaminases were observed; in randomized studies of the fixed 80 mg monthly dose, ALT and AST elevations >3× ULN occurred in 32% of patients with inhibitors and 18% of patients without inhibitors ^[4].
Common adverse reactions: Viral infection, nasopharyngitis, and bacterial infection were listed as common adverse reactions in the prescribing information ^[3]^[4].
Immunogenicity: Transient antidrug antibodies were reported in clinical trials; a Cochrane summary noted transient antibodies to fitusiran and reported 4% (3/80) participants with transient antidrug antibodies in one trial, with no observed effect on antithrombin lowering in that report ^[1].

Study Design

The approval was supported by randomized, multicenter, open-label parent studies ATLAS-INH (N=57; 2:1 randomization to fitusiran 80 mg monthly vs on-demand BPA in participants with inhibitors) and ATLAS A/B (N=120; 2:1 randomization to fitusiran 80 mg monthly vs on-demand CFC in participants without inhibitors), with enrollment into the long-term extension ATLAS-OLE (227 participants rolled over) where an antithrombin-directed dosing regimen (AT-DR) was implemented and 213 patients transitioned to the AT-DR targeting AT activity 15–35% ^[5]. Clinicians should consult current prescribing information for full dosing guidance. The FDA approval date is 2025-03-28 and the label includes recommended AT monitoring time points at Months 1, 3, 5, and 6 and guidance on dose modifications based on measured AT activity ^[5]^[4]. Details on trial eligibility exclusions (e.g., pre-existing thrombophilia) and the AT-DR dosage algorithm are in the full prescribing information ^[5]^[4].

FAQ

Q1 What is QFITLIA (fitusiran) approved for?

QFITLIA is approved for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients aged 12 years and older with hemophilia A or B with or without factor VIII or IX inhibitors. The indication and approval date are specified in the FDA label and prescribing information. Clinicians should refer to the full prescribing information for patient selection and monitoring requirements.

Q2 How does fitusiran work?

Fitusiran is a double-stranded small interfering RNA (siRNA) that targets antithrombin (AT) messenger RNA, causing degradation of AT mRNA through RNA interference and thereby reducing plasma antithrombin levels. Lowering AT increases thrombin generation to help prevent or reduce bleeding episodes in patients with hemophilia A or B. This siRNA mechanism and the antithrombin-directed dosing approach are described in the approved labeling.

Q3 What is the recommended dose of QFITLIA?

The FDA-approved starting regimen is 50 mg administered subcutaneously once every 2 months, with subsequent dose and/or frequency adjustments guided by measured antithrombin activity to maintain an AT activity target range of 15–35%. The label provides specific AT monitoring time points and a dose-modification algorithm. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of QFITLIA?

The prescribing information lists viral infection, nasopharyngitis, and bacterial infection among the most common adverse reactions. The label and safety data also highlight serious risks observed in clinical studies, including thrombotic events, acute and recurrent gallbladder disease (cholelithiasis and cholecystitis), and liver enzyme elevations; transient antidrug antibodies were reported in trials. The label describes monitoring and management recommendations for these risks.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Fitusiran for Hemophilia A/B: Median Treated ABR 3.7

FDA Approves Fitusiran for Hemophilia A/B: Median Treated ABR 3.7

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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