Qfitlia (fitusiran) / Sanofi, Alnylam - LARVOL DELTA

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

Advances in Development of Drug Treatment for Hemophilia with Inhibitors. (PubMed, ACS Pharmacol Transl Sci) - "More recently, emicizumab, a bispecific antibody that mimics the function of activated clotting factor VIII, has demonstrated favorable efficacy for prophylaxis in patients with hemophilia A and inhibitors, representing a promising new therapeutic strategy...This review summarizes the current understanding of the pathophysiology of inhibitor development in hemophilia, outlines existing treatment options, and discusses advancements in novel therapeutic biologics, including a recombinant activated clotting factor VII variant (marzeptacog alfa), a new bispecific antibody (Mim8), antitissue factor pathway inhibitor antibodies (concizumab and marstacimab), and small interfering RNA targeting antithrombin (fitusiran). All of these agents are administered subcutaneously, with some offering the convenience of less frequent dosing (e.g., weekly or monthly). These potential drug candidates may provide significant benefits for the prophylaxis or treatment of bleeding disorders in..."

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

Reduced Doses of Factor Concentrates and Bypassing Agents to Treat Breakthrough Bleeds in Patients with Hemophilia A and B on Fitusiran Antithrombin-Based Dosing Regimen: ATLAS-OLE (ASH 2024) - P3 | "These results support the hemostatic capacity of fitusiran prophylaxis which led to a reduction in the number of bleeds and the amount of CFC/BPA required for the management of breakthrough bleeding events. These data further support the modeled factor equivalency of 20-40% in both PwHA and PwHB on fitusiran prophylaxis."

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

Gene Therapy and Hemophilia A: What Is the Future of Curative Therapy in the Age of Emicizumab? (ASH 2024) - "Additionally, the beneficial results seen in hemophilia A gene therapy clinical trials have occurred with meaningful challenges. This talk will review the risks and benefits of gene therapy for hemophilia A and consider them within the context of therapies (emicizumab and Fc-VWF-XTEN fusion protein-eht) that have shown consistent benefit compared with previously available factor VIII products as well as other promising therapies (Mim8, fitusiran, concizumab, and marstacimab) in late-stage clinical trials."

Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Mechanistic Modeling to Support Hemostatic Equivalency of Antithrombin Lowering in People with Hemophilia A or B (ASH 2024) - P3 | "This analysis predicted similar factor equivalency of 20-40% in both PwHA and PwHB for the target therapeutic range of fitusiran (15-35% AT). Clinical data on the efficacy and safety of treatment of breakthrough bleeds with reduced dosing of CFC/BPA further support these results."

Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases • A2M

Innovations in Hemophilia Research: Fitusiran, An Investigational Rebalancing Agent for the Treatment of Hemophilia (ASH 2024) - "Sponsored by Sanofi For in-person participants only"

Hematological Disorders • Hemophilia • Rare Diseases