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 | Active, not recruiting | Sponsor: Genzyme, a Sanofi Company | Trial completion date: Aug 2028 ➔ Dec 2026 | Trial primary completion date: Feb 2028 ➔ Aug 2026

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

Rebalancing agents in hemophilia: knowns, unknowns, and uncertainties. (PubMed, Haematologica) - "Fitusiran is a small interfering RNA agent that reduces antithrombin synthesis in hepatocytes, favoring a procoagulant state. Other promising rebalancing agents are concizumab and marstacimab, which selectively bind to the K2 domain of the tissue factor pathway inhibitor, thus restoring thrombin generation. SerpinPC is a subcutaneous biological inhibitor that blocks the anticoagulant activated protein C pathway, while VGA039 is a monoclonal antibody that targets its cofactor protein S. Although the available clinical data are promising, several important challenges remain. These include the thrombotic risk of rebalancing agents, perioperative and bleeding management, availability in low-income countries, efficacy and FVIII equivalence compared to existing treatments, ideal target populations, and potential application in other hemostatic disorders. The primary aim of this review is to summarize the best available evidence on these novel rebalancing agents, while..."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Utilising Thrombin Generation Assay to Guide Co-Administration of Factor Therapies With Fitusiran. (PubMed, Haemophilia) - No abstract available

Journal

Press Release: Q2: double-digit sales and solid business EPS growth. 2025 sales guidance is now high single-digit growth, at upper end of range (GlobeNewswire) - "ALTUVIIIO (hemophilia A) sales were €291 million of which 82% were in the US. Growth was driven by continued patient switches from older plasma-derived and recombinant factor medicines and to a lesser extent from non-factor treatments. Rest of World sales of €53 million benefited from the launch in Japan and supply sales to the collaborator Sobi. The hemophilia A franchise (ALTUVIIIO and Eloctate combined) sales were €356 million and increased by 41.1%, primarily driven by ALTUVIIIO’s strong performance of €291 million, while Eloctate contributed €65 million...Rezurock (chronic graft-versus-host disease, third line) sales were €132 million and increased by 21.1%, driven by launches gaining further momentum in Europe (sales of €14 million) and in Rest of World (sales of €11 million), including in China...Cablivi (acquired thrombotic thrombocytopenic purpura) sales were €69 million...Qfitlia (hemophilia A and B) sales were €1 million..."

Sales • Chronic Graft versus Host Disease • Hemophilia • Hemophilia A • Hemophilia B • Thrombocytopenic Purpura

Rebalancing therapy for congenital hemophilia (PubMed, Rinsho Ketsueki) - "The anti-TFPI agents concizumab and marstacimab are administered subcutaneously and have been approved for use in Japan. The siRNA drug fitusiran is used as an anti-AT agent that reduces the synthesis of AT, and SerpinPC as an anti-APC agent that specifically inhibits APC. This article will outline the concept of rebalancing therapy and the results of clinical trials, as well as precautions and potential issues during treatment."

Journal • Review • Hematological Disorders • Hemophilia • Rare Diseases

Fitusiran (Qfitlia) for hemophilia A and B. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Fitusiran: First Approval. (PubMed, Drugs) - "Fitusiran has the potential to be administered less frequently than other prophylactic treatments for haemophilia. This article summarizes the milestones in the development of fitusiran leading to this first approval for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and paediatric patients aged 12 years and older with haemophilia A or B with or without factor VIII or IX inhibitors."

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

PHYSICIANS OPTIMISTIC ABOUT NEXT EVOLUTION IN HEMOPHILIA PATIENT CARE (EHA 2025) - "Advancements in therapy are moving beyond factor replacement, with novel approaches such as gene therapy and non-factor therapies, including emicizumab, marstacimab, concizumab, fitusiran, and Mim8...The greatest challenges were cited as selecting the best treatment option (30%), patient adherence (28%) and securing insurance coverage (20%) - especially for newer options.45% of hematologists have made changes to the way they manage hemophilia A patients in the past year with more adoption of emicizumab and efanesoctocog alfa, for which they report high satisfaction... Managing hemophilia patients throughout their lifetime is challenging for hematologists as they aim to improve patient quality of life and lifestyle. Newer options are providing better efficacy for different patient types and with favorable administration. As these options are approved and launched, hematologists expect many patients will be candidates and they will quickly begin prescribing these agents as..."

Clinical • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Musculoskeletal Pain • Pain • Rare Diseases

Antithrombin activity measurement via the INNOVANCE Antithrombin assay to manage fitusiran dosing (ISTH 2025) - "Therapeutic doses of multiple medications potentially being used by the hemophilia population (e.g., FVIII, FIX, FVIIa) were demonstrated to not interfere with the assay. LoQ was shown to be 7% of norm, which ensures that the measuring range is suitable to monitor patients treated with fitusiran."

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

FX and FVIIa/FX product enhances coagulation potential in antithrombin-reduced hemophilia model (ISTH 2025) - "Aims To assess the coagulation potential of pd-FVIIa/FX or FX supplementation in AT-reduced PwH model in vitro (fitusiran-treated)...We previously reported that additional FX alone augmented emicizumab-driven hemostasis...The addition of FX to FVIII-depleted or FIX-depleted FX-deficient plasmas increased TG potential dose-dependently. Moreover, the addition of FX increased FVIIa/TF-triggered FXa generation dose-dependently."

Hematological Disorders • Hemophilia • Rare Diseases

Low incidence of anti-drug antibodies to fitusiran in people with hemophilia A or B with or without inhibitors (ISTH 2025) - "No participants discontinued due to ADAs. Table or Figure Upload"

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

Fitusiran-treatment modulates the ratio between alpha- and beta-antithrombin isoforms (ISTH 2025) - "This was also found for fitusiran-treated FVIII-KO mice, with the high/low salt activity ratio being increased 5-6-fold in fitusiran-treated versus untreated mice (4±1 vs 0.7±0.1, p<0.0001).Immunoprecipitation experiments confirmed relative increase of the beta-AT/alpha-AT ratio in both human and murine plasma. Importantly, the beta-AT/alpha-AT ratio remained unchanged in supernatants of untreated and fitusiran-treated hepatocytes, suggesting that changes in this ratio occurs after secretion into circulation."

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Pharmacodynamics and pharmacokinetics of fitusiran antithrombin-based dose regimen (AT-DR): clinical and population modeling data (ISTH 2025) - P3 | "Median (IQR) time to reach final dose was 111 days (0; 280). Table or Figure Upload"

Clinical • PK/PD data • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Association of antithrombin levels with efficacy of fitusiran prophylaxis in people with hemophilia A or B with and without inhibitors: a predictive modeling approach (ISTH 2025) - "A monotonic increasing relationship between ABR and AT levels was confirmed by modelling and simulation, with a median (95% CI) ABR of 0.73 (0.48, 1.05) at 10% AT activity levels, 2.31 (1.69, 3.18) at 15%, and 4.58 (3.55, 6.30) at 35% (Figure 1). Table or Figure Upload"

Clinical • Predictive model • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases • Thrombosis

ISTH: new data highlight innovation from Sanofi’s pipeline in rare diseases (Sanofi Press Release) - "New data from 18 abstracts, including five oral presentations, will be presented at the 33rd congress of the International Society on Thrombosis and Haemostasis (ISTH) in Washington D.C., US from June 21 to 25, 2025, highlighting Sanofi as a leader in hemophilia committed to rare blood diseases. Data to be presented expand on the potential of rilzabrutinib to address the underlying immune dysregulation of immune thrombocytopenia (ITP) and strengthen Sanofi as a leader in hemophilia with ALTUVIIIO and the newly launched Qfitlia, aimed at providing more treatment options to help improve patients’ lives."

Clinical data • Hemophilia • Thrombocytopenia

Qfitlia (fitusiran). (PubMed, Clin Ther) - No abstract available

Journal

Prediction of Interspecies Translation for Targeting Delivery Coefficients of GalNAc-siRNA Silencing Apolipoprotein C-III Using a Mechanistic Minimal Physiologically Based Pharmacokinetic/Pharmacodynamic Model. (PubMed, Clin Pharmacokinet) - "This study successfully constructed the mPBPK-PD model and conducted interspecies extrapolation for a GalNAc-siRNA targeting APOC3. Promising quantitative insights into a hepatic-targeted GalNAc-siRNA delivery system are provided to characterize the unique temporal disconnection of PK/PD properties and evaluate the key in vivo delivery processes. It will promote model-informed strategies and quantitative mechanistic understanding to support efficient drug development, evaluation, and clinical application of this modality in the future."

Journal • PK/PD data • AGO2

Press Release: Sanofi: strong Q1 performance and 2025 guidance confirmed (Sanofi Press Release) - "ALTUVIIIO (hemophilia A) sales were €251 million of which 87% were in the US. Growth was driven by continued patient switches from older plasma-derived and recombinant factor medicines and to a lesser extent from non-factor treatments. Rest of World sales of €33 million benefited from the launch in Japan and sales to the collaborator in Europe....Qfitlia (hemophilia A and B) was approved in the US on March 28, 2025, with first sales recorded at the beginning of Q2 2025. Dupixent sales were €3,480 million and increased by 20.3%. Global sales were driven by increased use in all approved indications, including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, prurigo nodularis, chronic spontaneous urticaria, and emerging use in COPD."

Sales • Asthma • Atopic Dermatitis • Chronic Obstructive Pulmonary Disease • Chronic Rhinosinusitis With Nasal Polyps • Chronic Spontaneous Urticaria • Eosinophilic Esophagitis • Hemophilia A • Hemophilia B • Prurigo Nodularis

Global Comparative Antithrombin Field Study: Impact of Laboratory Assay Variability on the Assessment of Antithrombin Activity Measurement at Fitusiran Clinical Decision-Making Points. (PubMed, Haemophilia) - "Siemens INNOVANCE AT assay can reliably measure AT activity at clinical decision points of 15-35% of normal and is most suitable for clinical management of patients taking fitusiran."

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

Soleo Health Selected as Exclusive In-Network Specialty Pharmacy for Qfitlia a Treatment Option for Adults With Hemophilia A and B With and Without Inhibitors (Businesswire) - "Soleo Health, an innovative leader and national provider of complex specialty pharmacy services, announced today it has been named the exclusive in-network specialty pharmacy for Qfitlia (fitusiran) by Sanofi, an innovative global healthcare company. Soleo Health will be the specialty pharmacy to dispense Qfitlia, the first antithrombin-lowering therapy for hemophilia."

Commercial • Hemophilia A • Hemophilia B

Fitusiran: The first approved siRNA therapy for hemophilia via reducing plasma antithrombin levels. (PubMed, Drug Discov Ther) - "This first-in-class agent demonstrates pan-hemophilia efficacy by targeting antithrombin to enhance thrombin activity, irrespective of factor VIII/IX deficiency status or plasma inhibitor presence. By pioneering a mechanism of antithrombin suppression, enabling sustained therapeutic action, and facilitating precision monitoring protocols, fitusiran has the potential to redefine hemophilia treatment paradigms."

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

FDA Approves Novel Treatment for Hemophilia A or B, with or without Factor Inhibitors (PRNewswire) - "Today, the U.S. Food and Drug Administration approved Qfitlia (fitusiran) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A or hemophilia B, with or without factor VIII or IX inhibitors (neutralizing antibodies)....Qfitlia's efficacy and safety were assessed in two multicenter, randomized clinical trials which enrolled a total of 177 adult and pediatric male patients with either hemophilia A or hemophilia B."

FDA approval • Hemophilia A • Hemophilia B

Safety and efficacy of a fitusiran antithrombin-based dose regimen in people with hemophilia A or B: the ATLAS-OLE study. (PubMed, Blood) - P3 | "Fitusiran AT‑DR was well tolerated and maintained bleed protection with as few as 6 injections per year. This trial was registered at www.clinicaltrials.gov as #NCT03754790."

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

Improved Overall Quality of Life and Treatment Satisfaction in Patients with Haemophilia Receiving Fitusiran: Analyses of Qualitative Semi-Structured Interviews of Participants in the ATLAS-OLE Trial (EAHAD 2025) - No abstract available

Clinical • HEOR • Interview • Hematological Disorders • Hemophilia • Rare Diseases

Partner-Led Program Highlights (Businesswire) - "Fitusiran – an investigational RNAi therapeutic partnered with Sanofi in development for the treatment of hemophilia A and B, with or without inhibitors. Sanofi expects to secure FDA approval by the PDUFA target action date of March 28, 2025."

FDA approval • PDUFA • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B