Qfitlia (fitusiran) / Sanofi, Alnylam - LARVOL DELTA

ATLAS-PEDS: Fitusiran Prophylaxis in Male Pediatric Subjects Aged 1 to Less Than 12 Years With Hemophilia A or B (clinicaltrials.gov) - P3 | N=32 | Completed | Sponsor: Genzyme, a Sanofi Company | Active, not recruiting ➔ Completed | Phase classification: P2/3 ➔ P3 | Trial completion date: Dec 2026 ➔ Aug 2026

Phase classification • Trial completion • Trial completion date • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Pediatrics • Rare Diseases

Transforming Hemophilia Treatment With Novel Rebalancing Agents: Clinical Studies and Practical Perspectives. (PubMed, Clin Appl Thromb Hemost) - "Rebalancing agents, including fitusiran (antithrombin-lowering small interfering ribonucleic acid), concizumab and marstacimab (tissue factor pathway inhibitor antagonists), are novel nonfactor therapies that restore hemostatic balance by targeting natural anticoagulants rather than replacing missing clotting factors. In addition, the use of rebalancing agents in pediatric patients (<12 years old) remains under investigation. While promising, successful implementation depends on individualized treatment approaches, appropriate monitoring protocols, and thorough patient education to improve current care for PwH."

Journal • Review • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Pediatrics • Rare Diseases

Bridging the Gap: A Systematic Review of Modern Hemophilia Therapies and Global Inequities in Clinical Trial Participation. (PubMed, Haemophilia) - "Modern therapies demonstrate strong efficacy and acceptable safety, with several approved agents. However, persistent global inequities in trial participation and access highlight the need for more inclusive research and equitable implementation strategies."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

New and novel pharmacotherapies for hemophilia A: an update. (PubMed, Expert Opin Pharmacother) - "In replacement therapy, efanesoctocog alfa maintains normal-to-near-normal factor VIII (FVIII) levels weekly by bypassing endogenous von Willebrand factor dependence. In non-replacement therapies, the focus centers on rebalancing agents - the anti-tissue factor pathway inhibitor (TFPI) monoclonal antibodies concizumab and marstacimab, and the antithrombin-targeting small interfering RNA (siRNA) fitusiran - as well as next-generation FVIII-mimetics like denecimig...Rebalancing therapies present potential thromboembolic risks, complex breakthrough bleed protocols, and standard laboratory assay interference (requiring antithrombin monitoring or specialized assays). Critical goals for contemporary hemophilia management include tailoring therapies through multidisciplinary collaboration, monitoring subclinical joint disease via point-of-care ultrasound, and implementing standardized, real-world protocols for emergency hemostasis."

Journal • Review • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • Rheumatology

Advances in treatments for hemophilia A/B with inhibitors: current treatment gaps and promising therapies. (PubMed, Expert Rev Hematol) - "A literature search was conducted using PubMed/MEDLINE, Embase, and Google Scholar for publications from January 2000 to March 2026 using combinations of the terms 'hemophilia A,' 'hemophilia B,' 'inhibitors,' 'immune tolerance induction,' 'bypassing agents,' 'emicizumab,' 'concizumab,' 'marstacimab,' 'fitusiran,' and 'gene therapy.' Relevant clinical trials, observational studies, guidelines, and review articles were evaluated. Despite transformative progress, important unmet needs remain, including incomplete hemostatic control, lack of predictive biomarkers, limited laboratory standardization, and inequitable global access. Future advances will depend on biomarker-guided personalized therapy, rational combination strategies, and integration of immune-modulatory and gene-based approaches to achieve durable tolerance and potentially curative outcomes."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Preventive care • Rare Diseases

New recombinant human Factor X to Optimize Chromogenic Anti-Factor Xa Antithrombin Assay (ISTH 2026) - "Background Measurement of Antithrombin (AT) activity is a key specialized assay for investigating thrombosis, and new applications arise with the introduction of Fitusiran for the treatment of hemophilia...These findings demonstrate that rFXa is a reliable raw material for manufacturing AT reagents and can ensure a stable supply for clinical laboratories. DOI*10.1016/j.rpth.2026.105894"

Cardiovascular • Hematological Disorders • Hemophilia • Rare Diseases • Thrombosis

Antithrombin Is the Main Physiological Inhibitor of Factor XIa: Implications for Hemostatic Control in Patients with Hereditary Angioedema and Antithrombin Deficiency (ISTH 2026) - "Aims To evaluate the physiological regulation of FXIa and its clinical implications Methods We studied plasma-purified α and βAT as well as 93 patients with ATD (89 heterozygotes, ~50% Anti-FXa activity; 4 homozygotes, ~20%), 1 haemophilia B patient on fitusiran (<5% Anti-FXa activity), 4 HAE patients with C1INH deficiency, and 33 healthy controls...In AT deficiency, quantifying anti ‑ FXIa activity provides prognostic information, supporting its integration into risk stratification and reinforcing the central role of FXI/FXIa in thromboinflammation.PI2400106_PI2400429_(ISCIII_NH_EU)and_23022_GERM_25, Page 2 ATTRACT_RYC2023_CNS2024_154203. Table or Figure Upload (1) Table or Figure Upload (2) DOI*10.1016/j.rpth.2026.105753"

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hemophilia • Hemophilia B • Hereditary Angioedema • Inflammation • Thrombosis

Hepatobiliary events in the Phase 3 ATLAS-OLE trial: 120-day safety update (ISTH 2026) - P3 | "These data demonstrate the enhanced safety profile of fitusiran with the AT-DR. Table or Figure Upload (1) Page 2 DOI*10.1016/j.rpth.2026.104838"

Clinical • P3 data • Gastroenterology • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Hepatology • Rare Diseases

Safety and efficacy of the fitusiran antithrombin-based dose regimen people with hemophilia A and B by age group (ISTH 2026) - P3 | "These data indicate the suitability of fitusiran prophylaxis for bleeding control for all PwH, irrespective of age . Table or Figure Upload (1) Page 2 Table or Figure Upload (2) DOI*10.1016/j.rpth.2026.104866"

Clinical • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Correction of haemostasis in severe Haemophilia A patients on Fitusiran – Assessment by ROTEM (ISTH 2026) - "ROTEM parameters and antithrombin (AT) levels. NS- not significant, p value: * ≤0.05,** ≤0.01,*** ≤0.001,**** ≤0.0001 DOI*10.1016/j.rpth.2026.104812"

Clinical • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • Thrombosis

Performance characteristics of Antithrombin laboratory assays in the low range concentrations and between assay consistence (ISTH 2026) - "Background With Fitusiran therapy, low to very low AT concentrations must be measured on plasma, requiring a new focus on AT assays for accuracy, sensitivity and trueness in the low range...Conclusions The various AT-FXa, AT-FIIa assays, and LIA can be safely used for measuring low-range AT concentrations till < 5%, while remaining accurate at the clinical threshold or in the normal range; all AT assays correlate correctly. Table or Figure Upload (1) Page 2 DOI*10.1016/j.rpth.2026.104082"

A chemiluminescent-based immunoassay to probe antithrombin antigen levels in plasma. (ISTH 2026) - "Background Fitusiran is a subcutaneous RNA interference therapy that suppresses the production of antithrombin (AT), thereby increasing thrombin generation to restore hemostasis in people with hemophilia...Subsequently the luminescent antithrombin assay will be compared to the diagnostic INNOVANCE antithrombin assay. DOI*10.1016/j.rpth.2026.104124"

Hematological Disorders • Hemophilia • Rare Diseases • Thrombosis

ATLAS-PEDS: Fitusiran Prophylaxis in Male Pediatric Subjects Aged 1 to Less Than 12 Years With Hemophilia A or B (clinicaltrials.gov) - P2/3 | N=32 | Active, not recruiting | Sponsor: Genzyme, a Sanofi Company | Phase classification: P3 ➔ P2/3

Phase classification • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Pediatrics • Rare Diseases

EVOLVING TREATMENT PRIORITIES IN HEMOPHILIA: PHYSICIAN AND PATIENT PERSPECTIVES ON CONVENIENCE, QUALITY OF LIFE, AND THE EMERGING ROLE OF REBALANCING AGENTS ACROSS THE US AND EU5 (EHA 2026) - "Rebalancing agents such as fitusiran (Qfitlia) , marstacimab (Hympavzi) , and concizumab (Alhemo) have introduced opportunities to reduce treatment burden and better align with patient lifestyle and preference, marking a fundamental evolution in disease management. Summary/Conclusion The emergence of rebalancing agents has accelerated a global paradigm shift toward shared decision-making and individualized care in hemophilia. As treatment expectations expand beyond bleed control to encompass lifestyle and mental well-being, convenience and patient voice have become defining measures of therapeutic success."

Clinical • HEOR • Hematological Disorders • Hemophilia • Rare Diseases

SFY17741: A Study to Test a Medicine (Fitusiran) for Preventing Bleeds in People With Severe Hemophilia Who Previously Received Preventive Treatment With Emicizumab (clinicaltrials.gov) - P4 | N=20 | Recruiting | Sponsor: Sanofi | Trial primary completion date: Sep 2026 ➔ May 2028

Trial primary completion date • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

A computational model-powered platform to inform the development of GalNAc-conjugated siRNA therapeutics. (PubMed, Mol Ther Nucleic Acids) - "This platform integrates preclinical and clinical data from all seven FDA-approved GalNAc-siRNA drugs-fitusiran, givosiran, inclisiran, lumasiran, vutrisiran, nedosiran, and plozasiran-spanning multiple species (mouse, rat, monkey, and human). The platform successfully predicted the PK and simulated the PD profiles of SAL0132 in humans, which demonstrated model-informed strategies to support efficient drug development of this modality. In conclusion, this platform enables users to predict GalNAc-siRNA PK/PD profiles across species by inputting specific model parameters, providing a powerful resource to guide the development of next-generation GalNAc-siRNA therapeutics."

Journal

RNA Therapeutics and Their Delivery Methods: A Paradigm for Hemophilia Management. (PubMed, J Drug Target) - "We synthesize clinical and preclinical data to contrast these modalities: siRNA strategies (e.g., fitusiran) have indicated ∼90% reductions in bleeding rates by rebalancing hemostasis independent of factor deficiency; LNP-mRNA platforms offer tunable, transient factor production without genomic integration risks; and CRISPR-based editing aims for permanent correction (up to 170% FIX expression in preclinical studies) but necessitates rigorous monitoring for off-target effects...We evaluate lipid nanoparticles (LNPs) as the current clinical gold standard for hepatic delivery, contrasting them against emerging polymeric systems, aptamer-conjugates, and exosomes designed to overcome rate-limiting barriers such as endosomal entrapment and renal clearance. By juxtaposing the immunogenic limitations of viral vectors, we conclude that next-generation RNA therapeutics, enabled by LNPs and GalNAc-conjugation, offer a strategic pathway to overcome the durability gap observed in..."

Journal • Review • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Fitusiran treatment modulates the ratio between alpha- and beta-antithrombin isoforms. (PubMed, Hemasphere) - "Both conditions were also associated with an up to twofold higher ratio of beta-AT/total AT. Altogether, our results demonstrate that reduced AT production modulates the ratio between beta-AT and alpha-AT."

Journal • Fibrosis • Gastroenterology • Hematological Disorders • Hemophilia • Hemophilia A • Hepatology • Immunology • Liver Cirrhosis • Rare Diseases

COST-EFFECTIVENESS OF FITUSIRAN PROPHYLAXIS VERSUS FACTOR VIII ON-DEMAND OR PROPHYLACTIC THERAPY FOR HEMOPHILIA A PATIENTS WITHOUT INHIBITORS (ISPOR 2026) - "From a US payer perspective, fitusiran prophylaxis was a cost-effective and cost-saving strategy for hemophilia A without inhibitors, providing superior health outcomes at lower overall cost compared with on-demand and prophylactic FVIII therapy."

Clinical • Cost effectiveness • HEOR • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

ATLAS-KIDS: A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B (clinicaltrials.gov) - P3 | N=85 | Recruiting | Sponsor: Sanofi

Trial initiation date • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Analytical validity of the INNOVANCE Antithrombin assay for the measurement of antithrombin activity at fitusiran clinical decision points. (PubMed, Res Pract Thromb Haemost) - "System comparability was confirmed with correlation coefficients of ≥0.997, slopes between 0.976 and 1.005, and intercepts between 0.5% and 2.1% of normal. The study confirms the INNOVANCE Antithrombin assay can precisely and reliably quantify AT activity at fitusiran clinical decision points and further supports its suitability for clinical management of people on fitusiran prophylaxis."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

New Treatment in Haemophilia: Challenges, Controversies and Uncertainties. (PubMed, Haemophilia) - "For nonfactor therapies-including emicizumab, concizumab, marstacimab and fitusiran-critical considerations for bleed management, surgical procedures, and transitioning between products, emphasizing that these agents are for prophylaxis only and require specific, often product-specific, concomitant factor or bypassing agent protocols for acute haemostasis. The role of corticosteroid immunomodulation-both prophylactic and reactive-is explored across clinical trials for haemophilia A and B, highlighting variable responses and the need for tailored strategies. This review synthesizes current evidence to help clinicians navigate this new therapeutic era, optimizing outcomes while mitigating the risks associated with these transformative treatments."

Journal • Review • Cardiovascular • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Immunology • Rare Diseases • Thrombosis

Nonfactor Replacement Treatment and Surgery in Haemophilia: Evidence From the Literature and Selected Clinical Cases. (PubMed, Haemophilia) - "The association of nonfactor prophylaxis with recombinant factors has provided safe, reproducible and effective results, with low rates of complications. However, the experience with rebalancing agents is still limited, and more real-world studies are needed to confirm the most appropriate approach."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Orthopedics • Rare Diseases

Therapeutic Alternatives to Recombinant Biologics: Mechanistic Framework, Clinical Evidence, and Selection Guidance. (PubMed, Drug Des Devel Ther) - "Clinical evidence from multiple FDA approvals demonstrates successful substitution: fitusiran achieves an 84-91% reduction in bleeding, iptacopan provides 61% transfusion independence, and deucravacitinib achieves 58.7% PASI-75 response. The future landscape will feature complementary modality use optimized for clinical scenarios, with AI-driven discovery and personalized selection potentially improving response rates from 30% to 60% to over 80%. Global access requires technology transfer, regulatory harmonization, and value-based pricing to bridge the gap between manufacturing cost advantages and realized patient benefits."

Journal • Review • Targeted Protein Degradation • CD36 • CYP2D6 • SCARB1

ATLAS-KIDS: A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B (clinicaltrials.gov) - P3 | N=85 | Recruiting | Sponsor: Sanofi

Trial initiation date • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases