Enjaymo (sutimlimab-jome) / Sanofi - LARVOL DELTA

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 • Bone Marrow Transplantation • CNS Disorders • Complement-mediated Rare Disorders • Dermatology • Gastrointestinal Disorder • 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

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

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 • Novel Coronavirus 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

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 • Oncology

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

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 • Pain • Pneumococcal Infections • Pneumonia • Rare Diseases • Renal Disease • Respiratory Diseases • Thrombocytopenia • Venous Thromboembolism • C1S • HP

Autoimmune Hemolytic Anemias: Challenges in Diagnosis and Therapy. (PubMed, Transfus Med Hemother) - "Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter...Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan)...Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging. This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Oncology • Rare Diseases • Thrombosis • Transplantation

Autoimmune haemolytic anaemias. (PubMed, Nat Rev Dis Primers) - "The management of wAIHAs has long been based around corticosteroids and splenectomy and on symptomatic measures and non-specific cytotoxic agents for CAD. Rituximab and the development of complement inhibitors, such as the anti-C1s antibody sutimlimab, have changed the therapeutic landscape of AIHAs, and new promising targeted therapies are under investigation."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

Torque Teno Virus Control by the Classical Pathway of Complement Activation-A Retrospective Analysis From a First-in-Human Trial Utilizing Sutimlimab. (PubMed, J Med Virol) - "Administering multiple lower doses (30 mg/kg) also showed a trend toward TTV load increase in healthy volunteers (1.8 log10 c/mL, 0-2.3 vs. 1.9, 1.3-2.8; p = 0.054) and a significant increase in transplant recipients (3.5 log10 c/mL, 3.0-6.1 vs. 4.1, 3.5-6.4; p = 0.004). This report suggests a role for the classical complement pathway in controlling TTV load."

Journal • P1 data • Retrospective data • Transplantation

Relationship Between Hemoglobin Levels and EQ-5D-5L Utility Index in Patients With Cold Agglutinin Disease (ISPOR-EU 2024) - P3 | "The current analysis aimed to investigate this relationship using data from the Phase 3 trials of sutimlimab in patients with CAD - CARDINAL (open-label single-arm with recent blood transfusion history - NCT03347396) and CADENZA (randomized double-blind placebo-controlled with no recent blood transfusion history - NCT03347422)... Our findings suggest a direct relationship between hemoglobin levels and EQ-5D-5L utility index scores in patients with CAD. Higher hemoglobin levels were associated with increased EQ-5D-5L utility index scores, indicating a beneficial effect on the quality of life among this patient population."

Clinical • Autoimmune Hemolytic Anemia • CNS Disorders • Complement-mediated Rare Disorders • Depression • Hematological Disorders • Mood Disorders • Pain • Psychiatry

Long-term safety profile of sutimlimab in adult Japanese patients with cold agglutinin disease. (PubMed, Int J Hematol) - "Hemoglobin and bilirubin levels improved during treatment but deteriorated after withdrawal and recovered on retreatment. Sutimlimab was well tolerated over a median of 3.8 years, with no new safety concerns identified during retreatment."

Journal • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Dermatology • Fibrosis • Gastroenterology • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Nephrology • Renal Disease

Combined Safety Data for Sutimlimab in Cold Agglutinin Disease: A Post-Hoc Analysis of the Phase 3 CARDINAL and CADENZA Trials (DGHO 2024) - P3 | "This combined analysis demonstrated that SUT 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 • Hepatology • 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

Sutimlimab in patients with cold agglutinin disease (CAD) – results of the Managed Access Program in Essen (DGHO 2024) - "This is the first report of the results of the MAP in Essen. Sutimlimab rapidly halted hemolytic activity and increased hemoglobin levels in this cohort of CAD patients. :"

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

New drugs for the treatment of primary immune thrombocytopenia (PubMed, Rinsho Ketsueki) - "Two thrombopoietin receptor agonists (eltrombopag and romiplostim), rituximab or splenectomy have been recommended for the treatment of glucocorticoid-resistant ITP in Japanese guidelines. In addition, the Syk inhibitor fostamatinib and FcRn inhibitor efgartigimod were approved in Japan for refractory ITP in 2023 and 2024, respectively. Clinical trials have also reported promising results for the new thrombopoietin receptor agonist avatrombopag, the BTK inhibitor rilzabrutinib, and the C1s inhibitor sutimlimab. These developments will usher in a new era in the treatment of ITP."

Journal • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura • SYK

REAL LIFE CASE SERIES OF HUMANIZED ANTIBODY ANTI-C1S OF COMPLEMENT PATHWAY, SUTIMLIMAB, FOR RELAPSED/REFRACTORY PATIENTS WITH COLD AGGLUTININE DISEASE (CAD) (SIE 2024) - "In 2019 the patient relapsed and was enrolled in a phase II study, available at our center, based on the oral administration of parsaclisib tb, an inhibitor of phosphatidylinositol-3 kinase (PI3Kδ), that discontinued after 7 weeks due to intolerance, albeit in partial remission. In November 2023, due to further recurrence with severe anemia (Hb 6 gr/dl), a third cycle of rituximab was administered but for persistence of severe anemia and positive biochemical hemolysis markers, she started treatment with azathioprine at a dose of 50 mg bis in die, without benefit...Effect of sutimlimab on Hb, haptoglobin and bilirubin level. *B: 30 days before Sutimlimab start."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • HP • PIK3CD

COMBINED SAFETY DATA AND THROMBOEMBOLIC EVENTS FOR SUTIMLIMAB IN COLD AGGLUTININ DISEASE: A POST-HOC ANALYSIS OF THE PHASE 3 CARDINAL AND CADENZA STUDIES (SIE 2024) - "Conclusion. SUT was generally well tolerated, and analysis of matched adjudicated TE events suggested a trend toward a reduced risk of TE ON-SUT versus PRE-SUT period."

Clinical • P3 data • Retrospective data • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hypertension • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Meningococcal Infections • Rheumatology • Systemic Lupus Erythematosus • Thrombosis • Venous Thromboembolism

SERUM BIOMARKERS AS PREDICTORS OF RESPONSE TO SUTIMLIMAB IN COLD AGGLUTININ DISEASE (CAD): A POST-HOC ANALYSIS OF PHASE 3 CARDINAL AND CADENZA STUDY DATA (SIE 2024) - "Conclusion. Predictive serum biomarkers for SUT response in patients with CAD may exist (such as reticulocyte count, reticulocyte index and IgM levels) and should be explored further."

Biomarker • P3 data • Retrospective data • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • HP

Sutimlimab for Cold Agglutinin Disease. (PubMed, J Adv Pract Oncol) - "Previously, eculizumab, a C5 inhibitor, had limited therapeutic effect for CAD. However, there is a paucity of medical literature on CAD and on sutimlimab in particular that is geared toward advanced practice providers (APPs). This article aims to provide APPs with a background in CAD and a focus on sutimlimab, assisting these providers in caring for patients with CAD receiving this therapy."

Journal • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Immunology • Thrombosis

Adult-onset severe paroxysmal cold hemoglobinuria after COVID-19 successfully treated with sutimlimab. (PubMed, Int J Hematol) - "This intervention was performed during a life-threatening hemolytic crisis, at a time requiring swift decision-making when specific tests to differentiate from other hemolytic anemias were not readily available. This case illustrates the potential of using a single dose of sutimlimab to manage life-threatening hemolytic crises in PCH, highlighting the significance of inhibiting the classical complement pathway."

Journal • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • Infectious Disease • Novel Coronavirus Disease • Paroxysmal Nocturnal Hemoglobinuria

The treatment strategies of autoimmune hemolytic anemia (PubMed, Zhonghua Xue Ye Xue Za Zhi) - "Rituximab with or without bendamustine is generally taken as the first-line regimen for cold autoimmune hemolytic anemia (cAIHA), while glucocorticoid and splenectomy are ineffective. Sutimlimab, a kind of complement inhibitor, has been approved for the treatment of cold agglutinin disease (CAD). In recent years, many new drugs have emerged as treatment options for AIHA. Emerging therapies, including B-cell-directed therapies, plasma cell-directed therapies, complement inhibitors, and phagocytosis inhibition, provide a new perspective for AIHA therapy, showing great potential for clinical applications."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

Sustained improvements in patient-reported outcomes after long-term sutimlimab in patients with cold agglutinin disease: results from the CADENZA study open-label extension. (PubMed, EClinicalMedicine) - P3 | "Continued inhibition of the classical complement pathway with sutimlimab results in meaningful long-term improvements in PROs (fatigue and QoL) in patients with CAD. Sanofi."

Journal • Patient reported outcomes • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Immunology