Enjaymo (sutimlimab-jome) / Sanofi - LARVOL DELTA

Pure IgA-mediated hemolytic anemia. a rare and challenging diagnosis of "Coombs Negative" hemolytic anemia, with successful management (ASH 2025) - "The patient received a course of dexamethasone IV 40 mg X 4 days and IVIG 1 gram/Kg, daily X2...She was transitioned to prednisone at discharge, and the dose was gradually tapered to 20 mg daily, without relapse 10 months later... Educational Points: "When you have eliminated all which is impossible, then whatever remains, however improbable, must be the truth," per Sherlock Holmes, in The Sign of Four, Sir Arthur Conan Doyle. This case illustrates a true diagnostic dilemma, as the standard approach to the diagnosis of severe, life-threatening hemolytic anemia was unrevealing. It was only when we considered an improbable etiology, i.e. pure IgA-mediated immune hemolytic anemia, despite repeated negative DAT, did we identify the diagnosis."

Anemia • Hematological Disorders • HP

Real-world outcomes of sutimlimab in cold agglutinin disease: A multicenter trinetx analysis (ASH 2025) - "Conclusions Prior to the development of sutimlimab, there were no approved treatments for cold agglutinin disease(CAD); traditional therapies such as rituximab and cytotoxic agents offered only partial or delayedresponses and were limited by frequent relapse and significant toxicity. This large-scale, real-worldanalysis confirms that sutimlimab confers durable hematologic response and favorable outcomes inpatients with CAD. This data supports the integration of sutimlimab into standard CAD management.Prospective studies are warranted to evaluate predictors of treatment durability, long termcomplications, and effect of discontinuation."

Clinical • Real-world • Real-world evidence • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Malignancies • Immunology • Infectious Disease • Rheumatology • Septic Shock • HP

Real-world safety of sutimlimab in patients with CAD/CAS: A multinational, multi-center, observational, prospective cohort Study (ASH 2025) - "Furthermore,1 death was reported in a patient with CAD (SAE of low right lung pneumonia) unrelated to sutimlimab.Adverse events of special interest (AESIs) were observed within the sutimlimab cohort in patientsdiagnosed with CAD, including 3 patients who experienced serious infections (sepsis, urinary tractinfection, positive Gram-negative rods blood culture [klebsiella], cellulitis, and bilateral pneumonia), 2patients who experienced arterial hypertension (reported as non-serious), and 3 patients withconcomitant use of rituximab; none of of these AESIs were considered related to sutimlimab. After a mean treatment duration of over 2 years, no new safety concerns were identified inthis updated analysis of CADENCE registry patients with CAD and CAS chronically treated withsutimlimab. Safety findings are consistent with earlier clinical trial data and continue to support the long-term safety profile of sutimlimab in patients with CAD. Final follow-up results are expected..."

Clinical • Observational data • Real-world • Real-world evidence • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Meningococcal Infections • Nephrology • Pneumonia • Pulmonary Arterial Hypertension • Respiratory Diseases • Septic Shock • Systemic Lupus Erythematosus

Dysregulation of the complement system in immune thrombocytopenia (ASH 2025) - "This issupported by promising results of recent trials of sutimlimab, a monoclonal antibody targeting C1s, inchronic ITP...These results suggest possible variations in the underlying pathways and pathophysiology ofdifferent ITP disease phases.In summary, our results corroborate existing data and introduce novel insights into specific complementcomponents and distinct pathway mechanisms across ITP disease phases. These observations could offernew tools for patient stratification in future clinical trials and treatments."

Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • CFB

NLRP3 inflammasome inhibition fails to prevent red blood cell lysis in PNH (ASH 2025) - "Experimental conditions included heat inactivated serum (56OC for 30 min toinactivate complement proteins), specific complement inhibitors including eculizumab (Ecu, terminalcomplement inhibitor, 0.34 µM ), factor d inhibitor (Fdi, alternative pathway 1 µM), and sutimlimab (Suti,0.041µM), pan-caspase inhibitor (Z-VAD-FMK, 5 µM) and Caspase 8 inhibitor (Z-IETD-FMK, 5 µM), andNLRP3 inhibitor (MCC950, 5µM), and NLRP3 inflammasome activator (Nigericin, 1µM). Our findings reinforce complement inhibition as the primary clinical strategy for PNH, withlittle evidence supporting inflammasome/caspase targeting for hemolysis. Although inflammasomeactivation may contribute to PNH-associated inflammation, its role in RBC destruction appears negligible."

Complement-mediated Rare Disorders • Hematological Disorders • Inflammation • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • CASP8 • NLRP3 • TINCR

Complement-induced procoagulant platelets in patients with antiphospholipid antibodies (ASH 2025) - "On certain occasions sera were heat inactivated at 56º C for30 min or pre-treated with IdeS (IgG cleaving enzyme) (10000 U/ml at 37º C for 30 min), eculizumab (1mg/ml), sutimlimab (C1s inhibitor) (1.5 mg/ml) and/or danicopan (Factor D inhibitor) (100 µM). Also, onother occasions platelets were pre-incubated with antagonists of C3aR (SB290157), FcgRIIa (IV.3) or C5aR1(Avacopan) (10 µM) before serum.ResultsWe found that although activation and responsiveness to agonists of platelets from aPL+/APS patientswere like those from healthy individuals, unstimulated platelets from APS patients exhibited higherphosphatidylserine (PS) exposure (19.6±3.9% vs 4.0±1.0% controls) and P-selectin expression (15.9±2.3%vs 8.6±1.8% controls) than controls suggesting induction of procoagulant activity...Pre-incubating platelets with FcgRIIa, C3aR or C5aR1 antagonistsdid not reverse the procoagulant activity induced by APS serum.ConclusionWe demonstrate..."

Clinical • Cardiovascular • Genetic Disorders • Hematological Disorders • Immunology • Thrombosis • ANXA5 • CASP3 • CASP7 • SELP

Real world use of sutimlimab in patients with cold agglutinin disease: An international study (ASH 2025) - "Prior CAD treatments (median 3, 1-4) includedcorticosteroids (31), rituximab (40), and rituximab–bendamustine (12). At the last follow up only one patient had died due toprogressive WM with sepsis. Sutimlimab confirmed to be an effective treatment in improving anemia andresolving transfusion dependence in more than 70% patients in the real world."

Clinical • Real-world • Real-world evidence • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Influenza • Lymphoma • Lymphoplasmacytic Lymphoma • Pneumonia • Respiratory Diseases • Septic Shock • Thrombosis • Waldenstrom Macroglobulinemia

Autoimmune Outcomes in Patients with Concurrent Autoimmune Disease Receiving CD19 CAR T-Cell Therapy for Lymphoma (ASH 2024) - "Products included axicabtagene ciloleucel (axi-cel), brexucabtagene autoleucel (brexu-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel)...Medications that were discontinued included hydroxychloroquine, rituximab, and sulfasalazine. The fourth patient, who had paraneoplastic cold agglutinin disease, experienced improvement in symptom burden but remained on sutimlimab (last follow-up 2 months post-CAR T-cell therapy)...CAR T-cell therapy may be a potential treatment option for patients with severe AID. Although our study was limited by a small sample size, these data support prospective trials to determine both the efficacy and toxicity of CAR-T cell therapy for patients with AID."

CAR T-Cell Therapy • Clinical • Anemia • Autoimmune Hemolytic Anemia • CNS Disorders • Complement-mediated Rare Disorders • Dermatology • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lymphoma • Multiple Myeloma • Multiple Sclerosis • Oncology • Psoriasis • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus

Optimizing Complement Inhibitor Monitoring in PNH and Beyond (ASH 2024) - "Results : In vitro addition of C5 inhibitors (eculizumab, ravulizumab, crovalimab) to healthy control serum demonstrated a dose-dependent increase of complement blockade in GVB++ buffer. In isolated AP buffer, we observed dose-dependent inhibition with increasing concentrations of eculizumab, danicopan (factor D inhibitor), iptacopan (factor B inhibitor), and pegcetacoplan (C3 inhibitor)...Interestingly, in the baseline and 1-week serum, either danicopan or sutimlimab completely inhibited AP activity...Using this assay, EVH can be more precisely defined as full blockade of complement activity with persistent evidence of hemolysis. Furthermore, the assay has applications for not only PNH but also other diseases in which complement inhibitors are indicated, such as atypical hemolytic uremic syndrome."

Anemia • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • CD46 • CD55 • CD59

Cold Agglutinin Disease (CAD) Real-World Evidence (CADENCE) Registry: Update to the Study Design of the First International, Prospective CAD Registry (ASH 2023) - P | "CADENCE is the first global registry for patients with CAD and will help advance understanding of the natural history and disease process of this rare condition. This registry will also assess the long-term safety and effectiveness of sutimlimab in patients with CAD in a real-world setting, providing clinicians with data that may help improve treatment practices."

Clinical • HEOR • Real-world • Real-world evidence • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Arterial Hypertension • HP

Efficacy of Sutimlimab in Improving FACIT-Fatigue Scores in Patients with Cold Agglutinin Disease: A Post-Hoc Analysis of the Phase 3 Cadenza (Part A) Study (ASH 2023) - P3 | "Number needed to treat to observe a sutimlimab-related FACIT-Fatigue benefit was 4. The proportion of severe FACIT-Fatigue answers for fatigue and energy items was noticeably lower in sutimlimab-treated patients at Week 26 compared to placebo, highlighting the effect of sutimlimab in improving almost all dimensions of FACIT-Fatigue scale."

Clinical • P3 data • Retrospective data • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Immunology • Inflammation

Targeting Complement Inhibition in Cold Hemolysis; A Multifaceted Approach Using Sutimlimab and Washed Red Cell Transfusions (ASH 2023) - "Over a period of two weeks, she received three doses of IVIG, prednisone, and 17 transfusions units of warmed red blood cells in the setting of persistent hemolytic anemia...The patient was kept warm and started on Danazol and Sutimlimab... Here, we describe a challenging case of CAS caused by a rare Pr autoantibody, with a failure of first-line treatments for CAS. This report is the first to describe the use of Sutimlimab as a treatment for CAS. After initiating Sutimlimab, the patient continued to experience significant hemolysis shortly after transfusions, exhibiting hemoglobinuria and an inadequate increase in hematocrit."

Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Novel Coronavirus Disease

The Bioluminescent Modified Ham Test Identifies the Classical Pathway As the Major Driver of Complement Activation in Atypical Hemolytic Uremic Syndrome and Primary Antiphospholipid Syndrome (ASH 2023) - "The complement specificity of the luminescent changes were demonstrated with heat inactivation, terminal complement blockade with eculizumab, and calcium/magnesium dependence. The relative contribution of CP to changes in luminescence was confirmed with the specific CP inhibitor sutimlimab as well as use of pathway specific buffers... The bioluminescent mHam test is an exquisitely sensitive real-time measure of abnormal complement activity. It is easy to perform, more closely approximates the complement regulators on renal endothelium, can be utilized for therapeutic monitoring, and has already offered novel disease insights through the use of specific pathway inhibitors. Although aHUS is traditionally categorized as a disorder of the AP, these results suggest the "trigger" mediating disease pathology is the classical pathway."

Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Genetic Disorders • Hematological Disorders • Nephrology • Thrombocytopenic Purpura • CD55 • CD59

Combined Safety Data for Sutimlimab in Cold Agglutinin Disease: A Post-Hoc Analysis of the Phase 3 Cardinal and Cadenza Studies (ASH 2023) - P3 | "The combined safety analysis of the Phase 3 CARDINAL and CADENZA studies (Part A and B) demonstrated that sutimlimab was generally well tolerated, with the type and frequency of TEAE consistent with an older and medically complex population."

Clinical • P3 data • Retrospective data • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Gastrointestinal Cancer • Hematological Disorders • Hepatocellular Cancer • Hypertension • Immunology • Infectious Disease • Inflammatory Arthritis • Liver Cancer • Lupus • Meningococcal Infections • Non Small Cell Lung Cancer • Oncology • Pneumonia • Retinal Disorders • Rheumatology • Solid Tumor • Systemic Lupus Erythematosus • Thrombosis

Cost-Effectiveness of Sutimlimab Versus Standard-of-Care in Transfusion Dependent Patients with Primary Cold Agglutinin Disease in the United States (ASH 2023) - P3 | "For SOC, we assumed that all patients undergo the costs and risks of chemoimmunotherapy with bendamustine-rituximab, followed by rituximab monotherapy and subsequent treatment with mycophenolate mofetil, with all patients remaining dependent on transfusion care. Sutimlimab is conventionally cost-ineffective compared to SOC in transfusion-dependent patients with CAD. Distributional cost-effectiveness analysis (DCEA) to potentially justify sutimlimab as an equitable therapeutic option despite cost-ineffectiveness in the United States context is needed."

Clinical • Cost effectiveness • HEOR • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

Classical Complement Inhibition By SAR445088 (BIVV020) in Adults with Cold Agglutinin Disease: Safety, Tolerability and Activity Results from the Open-Label, Non-Randomized, Single-Dose Phase 1b Study (ASH 2023) - "The classical complement inhibitor sutimlimab, is the first approved pharmacotherapy for treating patients with CAD. SAR445088 was generally well tolerated; no safety concerns were identified in patients with CAD. A single IV dose of SAR445088 led to classical complement inhibition, control of hemolysis, and improvement in anemia, which was sustained for 15 weeks."

Clinical • P1 data • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Meningococcal Infections

First Interim Analysis of Patients with Cold Agglutinin Disease (CAD) Patients and the Sutimlimab-Treated Subgroup from the Cadence Registry (ASH 2024) - P | "At enrollment, among the pts receiving ongoing CAD treatment other than SUT (n=33), the most common treatments were rituximab (15.2%), folic acid derivatives (57.6%), direct factor Xa inhibitors (12.1%) and erythropoietin (12.1%). This initial real-world data on SUT-treated pts is consistent with results from clinical trials, demonstrating the benefit of SUT in managing anemia and hemolysis, and in addressing PROs. Further analyses will provide more insights about the natural history of CAD and CAS and long-term clinical outcomes of SUT."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders

A Rare Case of Cold Agglutinin Mediated Hemolytic Anemia, Thrombocytopenia, Acute Renal Failure, and Venous Thromboembolism Due to Mycoplasma Pneumoniae infection: A Toxic Combination (ASH 2024) - "The patient received treatment with cryoprecipitate, FFP and PRBC, and doxycycline...A decision is made to start the patient on sutimlimab (complement C1s inhibitor), and pneumococcal and meningococcal vaccinations are administered in preparation for the sutimlimab therapy.Discussion : Only a few case reports of secondary CAHA have been described in the literature...Corticosteroids, cytotoxic medications, and plasmapheresis are of limited value in secondary CAHA, but may be recommended in refractory cases.Conclusion : CAHA is a rare disorder that may occur in patients presenting with M. pneumoniae infection. It is, therefore, imperative to have a high index of suspicion in patients presenting with pneumonia and hemolysis, so as to ensure early diagnosis and prompt treatment."

Clinical • Acute Kidney Injury • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Cough • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Inflammatory Arthritis • Lymphoma • Meningococcal Infections • Oncology • Pneumococcal Infections • Pneumonia • Rare Diseases • Renal Disease • Respiratory Diseases • Thrombocytopenia • Venous Thromboembolism • C1S • HP

Anti-Complement Therapy Decreases Endogenous Thrombin Potential in Patients with Cold Agglutinin Disease (ASH 2024) - "All patients on therapeutic AC were on rivaroxaban...The 2 patients on AC and sutimlimab had a mean ETP of 622.58nM.min, lag time of 6.16min, and peak of 97.23nM...Given the limited sample size, it will be important to expand this study to a larger number of centers and patients to verify our findings. Robust knowledge of the thrombotic potential of patients with CAD as well as the effects of various therapeutic interventions for CAD will better inform clinicians regarding morbidity risks and treatment decisions for this rare disease."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Rare Diseases • Thrombosis

Complement Biosensors Can be Used to Identify Classical Pathway and Alternative Pathway Dysregulation in Complement-Mediated Thrombotic Microangiopathy (ASH 2024) - "This stimulus is blocked by sutimlimab and eculizumab, but not by alternative pathway inhibitors including, AMY-101 (C3 inhibitor), iptacopan (factor B inhibitor, FBi), danicopan (factor D inhibitor, FDi), or even a combination of all three. In summary, these biosensors can be used as a sensitive method for investigating individual mechanisms of complement pathway activation in CM-TMA and help monitor therapeutic complement blockade. Identification of a CP stimulus in CM-TMA provides a potential explanation for ~50% of CM-TMA patients who lack an AP "driving" variant and suggests at least a subset of CM-TMA is characterized by a breakdown of IgM immunologic tolerance."

Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Nephrology • Thrombocytopenic Purpura • CD46 • CD55 • CD59

Iptacopan Monotherapy in Patients with Cold Agglutinin Disease: Phase II Study Results (ASH 2024) - P2 | "Standard of care for acute CAD has consisted of blood transfusions, plasmapheresis, high-dose steroids and/or early use of rituximab. More recently, several complement inhibitors have shown clinical benefit in refractory CAD, with the classical pathway inhibitor sutimlimab (Röth et al...Iptacopan was well tolerated, with no unexpected safety findings. These results are promising but require confirmation in a larger study."

Clinical • Monotherapy • P2 data • Acute Kidney Injury • Anemia • Autoimmune Hemolytic Anemia • Breast Cancer • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Immunology • Musculoskeletal Diseases • Nephrology • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Solid Tumor • HP

Challenges in PNH and CAD Management Revealed through Educational Interventions over Three Years (ASH 2024) - "This could be explained by the paucity of targeted therapies in 2020, prior to the approval of the first CAD therapy (sutimlimab) in early 2022...These insights necessitate ongoing clinician education and inform the clinical strategies included in future initiatives. These activities were supported by independent educational grants from Apellis Pharmaceuticals and Sanofi."

Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Cold Agglutinin Disease: Virtual Patient Simulation Improves Performance in Diagnosis and Management (ASH 2024) - "In case 2, pre-CG, very few hematologists selected appropriate treatments for the patient who was diagnosed with CAD, but post-CG, there were significant improvements : 26% selected sutimlimab vs 5% pre-GC (P <.01); 24% selected rituximab (RTX) vs 3% pre-GC (P <.01); 13% selected RTX + bendamustine vs 0% pre-GC (P <.05). Conclusions These results demonstrate the success of immersive, online simulation education in improving performance in in recognizing signs and symptoms of CAD, appropriately diagnosing, assessing treatment and needed follow-up as well as adequate patient education. Areas of continued educational need include diagnostic test interpretation to be able to correctly diagnose CAD, patient education needs, treatment selection, and implementation of preventative vaccines."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

Iptacopan Monotherapy in Patients with Cold Agglutinin Disease: Phase II Study Results (ASH 2024) - P2 | "Standard of care for acute CAD has consisted of blood transfusions, plasmapheresis, high-dose steroids and/or early use of rituximab. More recently, several complement inhibitors have shown clinical benefit in refractory CAD, with the classical pathway inhibitor sutimlimab (Röth et al...Iptacopan was well tolerated, with no unexpected safety findings. These results are promising but require confirmation in a larger study."

Clinical • Monotherapy • P2 data • Acute Kidney Injury • Anemia • Autoimmune Hemolytic Anemia • Breast Cancer • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Immunology • Musculoskeletal Diseases • Nephrology • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Solid Tumor • HP

"Sutimlimab as a Bridge to Recovery in a Life-Threatening Case of Secondary Cold Agglutinin Syndrome" (DGHO 2025) - "The patient subsequently received azithromycin. The patient is currently under active surveillance with regular laboratory follow-up, and after 4 months there have been no indications of relapse. Supportive care and treatment of the underlying trigger is the standard of care for secondary CAS. Although spontaneous improvement cannot be completely excluded, the rapid clinical response strongly suggests that Sutimlimab was effective in halting intravascular hemolysis, preventing further organ dysfunction, and facilitating the patient's recovery."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Pneumonia • Renal Disease • Respiratory Diseases • HP