Qfitlia (fitusiran) / Sanofi, Alnylam - LARVOL DELTA

Fitusiran for Hemophilia A and Hemophilia B (ASH 2025) - "My presentation will detail the FDA approval of Fitusiran for Hemophilia A and B"

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

Efficacy, quality of life, and safety of non-clotting factor prophylaxis in Hemophilia A and b: A meta-analysis across inhibitor status (ASH 2025) - "Eligible studies included double-arm randomized controlled trials (RCTs) comparing non-clotting factor prophylaxis (emicizumab, fitusiran, or concizumab) with on-demand treatment in patients with hemophilia A or B, regardless of inhibitor status. Compared to on-demand therapy, non-factor prophylactic therapies significantly reduce bleeding episodes, improve quality of life, and increase the likelihood of zero bleeds in patients with hemophilia. Although associated with a higher rate of adverse events, the therapies themselves did not increase the risk of serious adverse events. While efficacy outcomes were similar across agents, cost differences may influence treatment selection.These findings support the clinical utilization of non-factor prophylaxis in managing hemophilia A and B, regardless of inhibitor status."

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

Efficacy and safety of the antithrombin siRNA fitusiran as prophylaxis in haemophilia a and B: A systematic review and meta-analysis (ASH 2025) - "Fitusiran significantly reduces bleeding rates and improves quality of life without a corresponding increase in adverse events, including thromboembolic complications. These findings underscore the therapeutic potential of fitusiran as a transformative treatment option in haemophilia care and warrant further integration into clinical practice guidelines and long-term safety surveillance."

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

New fitusiran 10 mg dose increases proportion of people with hemophilia within target antithrombin range of 15–35% (ASH 2025) - P3 | "Overall, these findings are the basis for the FDAs decision to include the lower dose of fitusiran to benefit a broader population with hemophilia A or B, regardless of inhibitor status. Real-world data collection of participants receiving AT-DR will further aid understanding of the effects of this lower fitusiran dose."

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

Evaluating the safety and tolerability of switching from emicizumab to fitusiran prophylaxis in adult males with severe hemophilia A, with or without inhibitors: SWITCH study, a trial in progress (ASH 2025) - "This poster will present early clinical trial date from a study assessing the safety of switching from emicizumab to fitusiran in patients with hemophilia A who are on emicizumab."

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

Experience with minor surgeries in people with hemophilia A or B with and without inhibitors receiving fitusiran (ASH 2025) - P1/2, P3 | "In total, 67% of dental surgeries and 87% of all minor surgerieswere performed without the use of antifibrinolytics. Overall, these data contribute to the growingevidence base for the perioperative management of PwH receiving fitusiran prophylaxis."

Surgery • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Ophthalmology • Orthopedics • Rare Diseases

Comparison of hemosil and innovance antithrombin assays using Hemophilia A plasma and antithrombin lowering (to mimic fitusiran) (ASH 2025) - "The SIL and INN AT assays are both licensed for the detection of physiologic AT deficiency. Both functionwell and demonstrate good concordance at higher AT levels (≥50%), but significant discrepancies arise atlower AT levels, particularly below 25%. Specifically, the INN assay, the only one approved in the US forfitusiran monitoring, consistently reports higher AT activity compared to SIL at lower target levels."

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

Evaluating the safety and tolerability of switching from emicizumab to fitusiran prophylaxis in adult males with severe hemophilia A, with or without inhibitors: SWITCH study, a trial in progress (ASH 2025) - P4 | "Secondary endpoints include: laboratoryassessments (peak thrombin generation and AT levels) from Day 1 to Month 4 of fitusiran treatment; emicizumab plasma concentrations up to complete washout (~Month 4 of fitusiran treatment); incidence,severity and seriousness of adverse events from Day 1 to Month 18 of fitusiran treatment; health-relatedquality of life measures from baseline to the end of the study; change in participant joint health; andannualized bleeding rate during the 14-month extension period.ConclusionThe SWITCH study will continue recruitment following evaluation of the 3 sentinel patients. This analysiswill provide critical evidence to inform healthcare providers on how to safely transition patients fromemicizumab to fitusiran, an important consideration in hemophilia clinical practice."

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

Efficacy and safety of fitusiran prophylaxis in people with haemophilia a or haemophilia B: A systematic review and meta-analysis (ASH 2025) - "Fitusiran prophylaxis is an effective therapy for reducing bleeding rates in patients withhemophilia A or B with inhibitors. While a similar trend was observed in patients without inhibitors, theresult was not statistically significant. The safety profile indicates an increased risk of TEAEs, most notablytransient elevations in ALT, but not an increase in severe adverse events."

Retrospective data • Review • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Infectious Disease • Musculoskeletal Pain • Rare Diseases • Respiratory Diseases

Real‑world experience with anti‑TFPI agent (Marstacimab) in severe and non‑severe hemophilia: First reported successful use in a female with non-severe hemophilia b (ASH 2025) - "Recent approval of rebalancing agents—includingMarstacimab, a tissue factor pathway inhibitor (TFPI) monoclonal antibody for people with hemophilia Aand B without inhibitors, along with Fitusiran and Concizumab—herald a new era of expanded, andeffective patient-friendly therapeutic options.To date, regulatory approvals and pivotal trials have focused predominantly on severe hemophilia (factorVIII or IX activity <1%), often excluding non-severe (1–5% activity) and female pwh...50% switchedfrom a CFC based prophylaxis while the remaining switched to weekly SQ regimen from on demandtherapy in the moderate cohort whereas 75% of severe Hemophilia A/B patients switched from CFC andremaining from previous Emicizumab prophylaxis... Our findings underscore the critical need to consider bleeding phenotype—not merely factorlevels—when selecting candidates for rebalancing therapies. Women with hemophilia endure recurrent,debilitating bleeds related to menorrhagia or obstetric..."

Clinical • Real-world • Real-world evidence • Cardiovascular • Gynecology • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Musculoskeletal Diseases • Obstetrics • Rare Diseases • Rheumatology

Tissue factor pathway inhibitor-reduced and antithrombin-reduced hemophilia state exhibit different coagulation responses to bypassing agents (ASH 2025) - "Fitusiran is an investigationalsiRNA which reduces antithrombin (AT) to rebalance hemostasis in PwH...In addition, previous basic studies have demonstrated that even FX supplementation augmentsemicizumab-driven hemostasis (Shimizu K. Thromb Haemost... FX or pd-FVIIa/FX supplementation increased coagulation potentials in TFPI-reduced PwHmodel plasmas and AT-reduced PwH model plasmas due to FVIIa/TF-induced activation of FX. However,caution is warranted because the effects of rFVIIa, pd-FVIIa/FX and FX were different between TFPI-reduced PwH state and AT-reduced PwH state."

Hematological Disorders • Hemophilia • Rare Diseases

High treatment compliance and tolerability with fitusiran antithrombin-based dose regimen in people with hemophilia A or B, with or without inhibitors: ATLAS-OLE study (ASH 2025) - P3 | "Other commonTEAEs included gastrointestinal disorders (n=65 [30.5%]), nervous system disorders (n=34 [16%]), andmusculoskeletal and connective tissue disorders (n=67 [31.5%]), of which arthralgia (n=22 [10.3%]) wasthe most common AE.ConclusionsThis analysis confirms that in participants receiving the AT-DR, fitusiran was associated with high overalllevels of compliance (96.0%) and was well tolerated as demonstrated by low discontinuation rates due toAEs (2.3%). The high treatment compliance observed in ATLAS-OLE is likely due to reduced treatmentburden afforded by the Q2M regimens (that 78% of participants were receiving), supporting the clinicalutility of fitusiran in PwHA or B, with or without inhibitors."

Compliance • Cardiovascular • CNS Disorders • Dermatology • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Hepatocellular Cancer • Infectious Disease • Mood Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Novel Coronavirus Disease • Pruritus • Rare Diseases • Rheumatology • Solid Tumor • Thrombosis

In vitro comparison of eptacog beta and eptacog alfa with antithrombin lowering (simulated fitusiran) using thrombin generation assay (ASH 2025) - "These results demonstrate that in vitro both eptacog beta and eptacog alfa similarly increase TG when ATlevels are reduced to fitusiran target ranges. Eptacog alfa doses of 45µg/kg, used to treat bleeds inpatients on fitusiran, had similar TG parameters to the 75µg/kg and 125µg/kg doses of eptacog beta. Thisdata provides in vitro proof of concept supporting the use of eptacog beta for the treatment ofbreakthrough bleeds of patients on fitusiran prophylaxis."

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

fss25-110: Advancing Hemophilia Care—Uniting Expert Insights and Community Voices to Shape the Future of Non-Factor Replacement Therapy (ASH 2025) - "This dynamic event combines expert panel discussions, real-world case challenges, and insights from patients and community HCPs to explore the latest data on novel therapies including fitusiran, concizumab, marstacimab, and Mim8. Through interactive polling and audience Q&A, attendees will gain practical guidance on integrating these therapies into personalized care strategies for patients with moderate to severe hemophilia A and B. Discover how to navigate evolving safety profiles, improve joint health outcomes, and tailor treatment based on patient needs and preferences. This symposium offers a comprehensive view of current challenges, cutting-edge solutions, and future directions in hemophilia management, equipping you with actionable insights to improve clinical practice."

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

The National Medical Products Administration (NMPA) in China has approved two innovative Sanofi medicines for rare hematologic diseases: Qfitlia (fitusiran) for hemophilia and Cablivi (caplacizumab) for acquired thrombotic thrombocytopenic purpura. (The Manila Times) - "Qfitlia is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in pediatric patients 12 years of age and older, and adults with severe hemophilia A (coagulation factor VIII deficiency, FVIII). This approval is based on data from the ATLAS phase 3 studies...Cablivi is the first Nanobody targeted therapy designed to treat acquired/immune-mediated thrombotic thrombocytopenic purpura (aTTP/iTTP) in adults and adolescents aged 12 or older weighing at least 40 kg."

China approval • Hemophilia A • Immune Thrombocytopenic Purpura

Cost-Savings Analysis of Fitusiran Prophylaxis: Reducing Breakthrough Bleeding Treatment Expenditure in the Kingdom of Saudi Arabia (ISPOR-EU 2025) - P3 | "For people with haemophilia (PwH) A without inhibitors, episodic treatments comprised octocog alfa, efmoroctocog alfa and rurioctocog alfa pegol for PwH A and nonacog alfa, albutrepenonacog alfa and eftrenonacog alfa for PwH B. Treatments included for PwH with inhibitors were factor VIII inhibitor bypassing activity (FEIBA) and eptacog alfa. In the KSA, fitusiran AT-DR prophylaxis may considerably reduce breakthrough bleed management costs in PwH versus CFC/BPA prophylaxis. Cost savings are predicted to be more substantial in PwH with inhibitors than in those without inhibitors."

HEOR • Hematological Disorders • Hemophilia • Rare Diseases

Cost-Savings Assessment of Fitusiran Prophylaxis in Minimizing Breakthrough Bleeding Treatment Expenses in the United Arab Emirates (ISPOR-EU 2025) - P3 | "The episodic treatments included were efmoroctocog alfa, octocog alfa and rurioctocog alfa pegol for people with haemophilia (PwH) A without inhibitors and albutrepenonacog alfa, nonacog alfa and eftrenonacog alfa for PwH B without inhibitors...A scenario analysis examined the impact of vial sharing. Among PwH without inhibitors, fitusiran AT-DR enabled per-bleed savings ranging from UAE Dirham (AED) 4,625 (efmoroctocog alfa) to AED 11,521 (rurioctocog alfa pegol) in PwH A and from AED 8,935 (nonacog alfa) to AED 30,053 (albutrepenonacog alfa) in PwH B. In PwH with inhibitors, fitusiran AT-DR usage generated per-bleed savings of AED 71,846 (FEIBA) to AED 90,761 (eptacog alfa). In the UAE, fitusiran AT-DR prophylaxis may considerably reduce costs associated with episodic treatments for breakthrough bleeds in PwH compared with CFC/BPA prophylaxis. PwH with inhibitors might have larger cost savings than those without inhibitors."

HEOR • Hematological Disorders • Hemophilia • 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

Fitusiran Population Pharmacokinetic and Pharmacodynamic Modeling Utilizing Phase 3 Clinical Trial Data to Confirm Doses Tested in Phase 3 Trials to Support an Antithrombin-Based Dose Regimen (ASH 2023) - P1, P1/2, P3 | "PopPK/PD model simulations confirm that the fitusiran AT-based dose regimen with a starting dose of 50 mg Q2M that can be escalated or de-escalated maintains the target AT range of 15–35% in the majority of PwH. It is predicted approximately 88% of PwH will require zero or one dose change. The efficacy and safety of the fitusiran AT-based dose regimen is being evaluated in ongoing clinical trials."

Clinical • P3 data • PK/PD data • Cardiovascular • Hematological Disorders • Hemophilia • 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

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

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

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

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

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=91 | Active, not recruiting | Sponsor: Sanofi | Trial primary completion date: Sep 2026 ➔ May 2027

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