Qfitlia (fitusiran) / Sanofi, Alnylam - LARVOL DELTA

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

Assessment of the Combined Effects of Emicizumab and Fitusiran with in Vitro Spiking of Simulated Fitusiran (using anti-thrombin antibody) into Plasma from Hemophilia a Patients on Emicizumab (ASH 2024) - "Conclusion From this early data, we show that AT lowering in the presence of emicizumab leads to an increase in peak thrombin and ETP and an optimal wash out period needs to be determined as patients are transitioned from emicizumab to fitusiran or vice versa. This also establishes a model for studying other combinations of non-factor therapies in hemophilia to inform transitions from one to the other."

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

Comparison of Drugs Used for Prophylaxis in Hemophilia a or B with Inhibitors: A Systematic Review and Frequentist Network Meta-Analysis of Randomized Clinical Trials (ASH 2024) - "NMA was registered on PROSPERO CRD42024532136.Results : In 6 RCTs (N=457), 38 patients were treated with fitusiran prophylaxis, 114 patients with concizumab prophylaxis, 147 patients with emicizumab prophylaxis, 17 patients with FEIBA NF prophylaxis, 26 patients with AICC prophylaxis, and 115 patients were only treated on demand without prophylaxis. Emicizumab and fitusiran had higher efficacy as compared to other prophylactic agents in hemophilia. More large-scale randomized head-to-head comparisons are needed to confirm these results."

Retrospective data • Review • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management in people with hemophilia A or B. (PubMed, Blood Adv) - P1, P1/2 | "Overall, fitusiran was well tolerated and effective bleeding control was maintained on an AT-based dose regimen. This trial was registered at www.clinicaltrials.gov as #NCT02554773."

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

Non-factor Therapies for Hemophilia: Achievements and Perspectives. (PubMed, Semin Thromb Hemost) - "Factor VIII (FVIII)-mimetic agents, such as emicizumab, have transformed the management of hemophilia A with inhibitors, offering a lower treatment burden and an effective alternative for those without inhibitors as well. Rebalancing agents, including anti-tissular factor pathway inhibitor agents (concizumab and marstacimab) and serpin inhibitors like fitusiran, have shown promising efficacy for patients with hemophilia B with inhibitors and other hemophilia subtypes...Unresolved issues include optimal management strategies for major surgeries and tailored approaches for safe use in older populations. This review highlights the progress and future potential of NFTs in treating persons with hemophilia."

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

ATLAS-NEO: A Study to Test a Medicine (Fitusiran) Injected Under the Skin for Preventing Bleeding Episodes in Male Adolescent or Adult Participants With Severe Hemophilia (clinicaltrials.gov) - P3 | N=79 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2028 ➔ Jun 2028 | Trial primary completion date: Apr 2026 ➔ Sep 2026

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

INTRINSIC ACTIVATED THROMBIN GENERATION FOR EFFICACY AND MONITORING OF FACTOR VIII REPLACEMENTS AND MIMETICS (EHA 2024) - "Various extended half-life FVIII products and non-factor(mimetics) agents (such as emicizumab and fitusiran) were introduced as alternatives...TG was assessed by means of the CAT assay,optimized, and validated for the new PPP Reagent INT (contact activator, 4 µM phospholipids) for increasedsensitivity towards octocog alfa and/or emicizumab... Intrinsic activated thrombin generation may be used for efficacy and monitoring of different Hemophilia Areplacement therapies. Future applicability for this PPP Reagent INT assay in monitoring SHA patients has to bestudied in more detail."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Intrinsic activated thrombin generation for efficacy and monitoring of emicizumab (ISTH 2024) - "Various extended half-life FVIII and non-factor products (such as emicizumab and Fitusiran) were introduced as alternatives... The TGA assay was optimized and validated for the new PPP Reagent INT (contact activator, 4 µM phospholipids) for measuring octocog alfa and emicizumab... TG in normal plasma triggered by PPP Reagent INT (36 replicates) was characterized by a lag time of 5.39±0.22 min, an endogenous thrombin potential (ETP) of 1451±38 nM.min, a peak height of 420±9 nM and a velocity index of 254±25 nM/min. The overall variability of the assay was < 10%(CV) for all parameters, with a within-run and between-day variation < 5%(CV). PPP Reagent INT failed to induce TG in plasmas deficient for FXII, FXI, FIX, or FVIII, whereas normal profiles were obtained for FVII deficient plasma."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Clinical Characteristics and Genotypic Landscape of Moderate to Severe Hemophilia A patients in a Hemophilia Treatment Center (ISTH 2024) - "2 patients received fitusiran, and 1 patient received activated factor VII (FVIIa)... Thirty-six male patients were reviewed with a median age of 30.5 years old (range 14 – 70). Nine patients (25%) had no significant family history. 6 patients (16.7%) had a documented history of inhibitors."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Surgical experience in people with hemophilia A or B with and without inhibitors receiving fitusiran (ISTH 2024) - "Sixty major surgeries (24 in inhibitor patients) were performed. In 47 (78.3%) major surgeries, BMG were followed, and reduced doses were used as perioperative prophylaxis. Four major surgeries were conducted without additional CFC/BPA."

Cardiovascular • Hematological Disorders • Hemophilia • Rare Diseases • Thrombosis

Hepatobiliary events in the fitusiran clinical development program with the revised AT-based dose regimen (ISTH 2024) - P1/2, P3 | "Overall, 286 participants were included in the analysis, with total patient-years of exposure of 486.0 (≥12 months exposure n=237) with the AT-DR. A total of 8/286 (2.8%) and 6/286 (2.1%) participants experienced ALT or AST elevations >3x upper limit of normal (ULN) with the AT-DR, respectively. The mean (SD) time to elevation was 241 (204.6), and 255 (240.6) days, respectively."

Clinical • Gastroenterology • Hematological Disorders • Hemophilia • Hepatology • Liver Failure • Rare Diseases

Fitusiran displays efficient pro-hemostatic activity in a mouse model of inducible factor X-deficiency (ISTH 2024) - "We developed a novel mouse model for FX-deficiency, expressing FX-levels below 0.5% of normal plasma (termed F10low-mice, controls were F10WT-mice). PT and aPTT were increased from 19±1s to 112±39s and 42±3s to 170±42s (p=0.0002), respectively. TG was severely reduced, with the Endogenous Thrombin Potential (ETP) being reduced from 894±58 nM•min to 149±126 nM•min."

Preclinical • Hematological Disorders • MX1