Fitusiran (Qfitlia) as a first-in-class RNAinterference therapeutic - targeting antithrombinfor prophylactic hemostasis in hemophilia

Sep 29, 2026

Fitusiran (Qfitlia) is an FDA-approved small-interfering RNA (siRNA) therapy designed for pan-hemophilia prophylaxis in both hemophilia A and B. It silences hepatic antithrombin (SERPINC1) to boost thrombin generation and restore hemostatic balance without relying on factor VIII or IX, including in patients with inhibitors. Extended-interval subcutaneous dosing improves adherence and convenience, with phase 3 trials reporting markedly lower annualized bleeding rates across ATLAS-INH, ATLAS-A/B, and ATLAS-OLE studies. Safety monitoring is emphasized due to risks such as thrombosis, gallbladder problems, viral or bacterial infections, and liver injury.

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Editorial

Background: hemophilia A/B and current prevention challenges

Mechanism of action: hepatic antithrombin silencing

Evidence from phase 3 ATLAS trials

Safety monitoring and management of adverse events

Clinical significance and potential to redefine prophylaxis

Editorial Fitusiran (Qfitlia) as a first-in-class RNAinterference therapeutic: targeting antithrombinfor prophylactic hemostasisin hemophilia Ehtisham Haider, MBBSa , FNU Preety, MBBSb , Mahnoor Sheikh, MBBSc , Riaz Akhtar, MBBSd ,Chijioke Vitalus Iloke, MBBSe , Malik Olatunde Oduoye, BScf ,* To the Editor, Hemophilia A and B are inherited bleeding disorders causedby low levels of clotting factors VIII and IX[1] . Despite improve -ments, current prevention methods with factor replacement ornonfactor agents like emicizumab still face challenges. Theseinclude a heavy treatment burden, the need for intravenousadministration, and occurrences of breakthrough bleeding[2] .Fitusiran (Qfitlia) is a new small-interfering RNA (siRNA) ther -apy that takes a different approach. It was first developed in2014 by Alnylam Pharmaceuticals[3] . It works by silencing theproduction of hepatic antithrombin (SERPINC1), which booststhrombin generation and restores hemostatic balance withoutrelying on factor VIII or IX. Early-phase studies showed that itreduced antithrombin levels in a dose-dependent manner, lead -ing to lasting improvements inhemostasis[4] . Despite advances in hemophilia care, significant challengespersist. Factor replacement therapy, the standard prophylacticapproach using factor VIII or IX concentrates, restores coagula -tion but is limited by poor adherence, frequent infusions,reduced quality of life, and inhibitor development[2] . Non-factortherapies, such as bispecific antibodies andrebalancing agents,improve convenience with less frequent dosing but do not fullyprevent bleeding and are largely restricted to hemophilia A[5] .A therapy that provides broad, durable prophylaxis for bothhemophilia A and B is needed. Fitusiran, the first FDA-approved aDepartment of Medicine, Punjab Medical College, Faisalabad, Punjab, Pakistan,bDepartment of Medicine, Jinnah Sindh Medical University, Karachi, Sindh,Pakistan, cDepartment of Medicine, Pak International Medical College, Peshawar,KPK, Pakistan, dDepartment of Medicine, Bacha Khan Medical College, Mardan,KPK, Pakistan, eDepartment of Community Medicine, Alex Ekwueme FederalUniversity Ndufu Alike Ikwo (AEFUNAI), Ebonyi, Nigeria and fDepartment ofResearch, The Medical Research Circle (MedReC), Goma, Democratic Republic ofCongo (DRC) Sponsorships or competing interests that maybe relevant to content are disclosedatthe end of this article. *Corresponding author. Address: Department of Research, The Medical ResearchCircle (MedReC), Goma 73, Democratic Republic of Congo (DRC). Tel.: +2349035928801. E-mail: malikolatunde36@gmail.com (M.O. Oduoye).Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is anopen access article distributed under the terms of the Creative CommonsAttribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where itispermissible to download and share the work provided itis properly cited. The workcannot be changed in any way or used commercially without permission from thejournal. Annals of Medicine & Surgery (2026) 88:45–46 Received 29 September 2025; Accepted 19 November 2025Published online 4 December 2025http://dx.doi.org/10.1097/MS9.0000000000004496 siRNA therapeutic, suppresses hepatic antithrombin to enhancethrombin generation, providing pan-hemophilia prophylaxis forboth hemophilia A and B, irrespective of inhibitor status.Administered subcutaneously with extended dosing intervals, itaddresses many drawbacks of existing therapies and may redefinetreatment paradigms. Through RNA interference, fitusiran selec -tively targets antithrombin mRNA in hepatocytes, reducing circu -lating levels and restoring thrombin generation. This mechanismrebalances coagulation even inpatients with inhibitors and repre -sents a unifying prophylactic strategy independent of factordeficiency[1,6] . Pivotal phase 3 trials demonstrate significant reduc -tions in annualized bleeding rates (ABRs) across hemophiliasubtypes, marking a

FAQs

How does fitusiran (Qfitlia) prevent bleeding in hemophilia?

It uses RNA interference to silence hepatic antithrombin (SERPINC1), which increases thrombin generation and rebalances coagulation without depending on factor VIII or IX.

What do the ATLAS-INH and ATLAS-A/B trials show about annualized bleeding rates?

ATLAS-INH reported a median ABR of 0.0 with monthly fitusiran versus 16.8 with on-demand therapy. ATLAS-A/B reported a median ABR of 0.0 versus 21.8 with on-demand therapy in patients without inhibitors.

What safety issues require monitoring during fitusiran therapy?

Monitoring focuses on thrombotic risk and prevention of gallbladder and liver complications. Doctors check antithrombin levels and liver blood tests before treatment and then monthly, and they watch for signs of gallbladder disease and blood clots.

Sep 29, 2026

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