Enjaymo (sutimlimab-jome) / Sanofi - LARVOL DELTA

A Case of Cold Agglutinin Disease With Transformation to High-Grade Lymphoma During Sutimlimab Treatment. (PubMed, Cureus) - "Subsequent chemotherapy with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone resulted in further improvement in anemia. This case highlights the importance of reassessing underlying conditions through BMB in cases where sutimlimab treatment is ineffective."

Journal • Autoimmune Hemolytic Anemia • B Cell Lymphoma • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • C1S

Cold agglutinin disease (CAD) (PubMed, Inn Med (Heidelb)) - "Knowledge of the specific clinical and laboratory hallmark changes of CAD with the early initiation of specific and targeted therapy or also referral to specialized centers has significantly improved the prognosis of the disease in recent years and reduced the suffering of patients."

Journal • Review • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Infectious Disease • Thrombosis

Enhanced immunocompatibility and hemocompatibility of nanomedicines across multiple species using complement pathway inhibitors. (PubMed, Sci Adv) - "However, both iptacopan and danicopan display poor efficacy with PEGylated liposomal doxorubicin. Sutimlimab, an inhibitor of the classical pathway, demonstrates poor efficacy with PEGylated liposomal doxorubicin, even in sera with anti-PEG antibodies...Iptacopan also alleviates nanoparticle-induced lethargy in rats and severe hypotension in dogs. These data suggest that complement inhibitors can enhance the immunocompatibility and hemocompatibility of nanomedicines in a donor-dependent manner."

Journal • Hypotension • Inflammation

A case of autoimmune hemolytic anemia with cold agglutinin disease post-operation for recurrent ovarian cancer. (PubMed, Int Cancer Conf J) - "Heated blood transfusions, along with rituximab and sutimlimab, led to clinical improvement. Stress from invasive surgery may activate the complement system, triggering cold agglutinin disease. Early diagnosis and treatment are crucial for preventing severe complications."

Journal • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Low Grade Serous Carcinoma • Nephrology • Oncology • Ovarian Cancer • Renal Disease • Solid Tumor

AT THE HEART OF COLD: EXPLORING AND ADVANCING THERAPIES IN COLD AGGLUTININ DISEASE BASED ON 7 CASES (EHA 2025) - "Treatment mainly involves avoiding cold exposure in conjunction with medical treatments, such as rituximab as first-line therapy, either alone or in combination with bendamustine. Cold agglutinin disease (CAD) is an idiopathic clonal B lymphoproliferative disorder without malignancy signs, characterized by the presence of antibodies capable of recognizing red blood cell antigens at low temperatures via complement activation. Its manifestations primarily include fatigue, anemia of varying severity, and ischemic signs exacerbated by cold. From a therapeutic perspective, only patients with poorly tolerated anemia below 8 g/dl, with transfusion dependence or severe circulatory symptoms, should be treated."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Congestive Heart Failure • Diabetes • Fatigue • Heart Failure • Hematological Disorders • Hypertension • Metabolic Disorders • Oncology • Retinal Disorders

ACCESS TO SUTIMLIMAB FOR COLD AGGLUTININ DISEASE THROUGH THE ORPHAN DRUG ACCESS PROTOCOL IN THE NETHERLANDS: INSIGHTS FROM THE FIRST YEAR (EHA 2025) - "Based on the limited data, it remains unclear which patients will benefit most from this long-term treatment compared to currently available fixed-duration treatment options such as rituximab or immunochemotherapy. The ODAP approach led to fast yet controlled access to sutimlimab for CAD patients in the Netherlands. It is too early to draw conclusions about the results of the ODAP sutimlimab while data collection is ongoing. We experienced that the indication committee improves the care of CAD patients through the monthly expert case discussions, preventing inappropriate use."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • C1S

EFFICACY AND SAFETY OF SUTIMLIMAB IN COLD AGGLUTININ DISEASE IN THE REAL WORLD (EHA 2025) - "Patients had received a median of 3 therapy lines (1-4) before sutimlimab, including steroids (N=20), rituximab (23), and rituximab-bendamustine (6)...Sutimlimab was given at 7.5 g iv/14 days after loading in 6 patients, and at 6.5 g in 19, either as single-agent in 16 or along with erythropoietin in 8 and prednisone in 1... Sutimlimab confirmed to be an effective treatment in improving anemia and resolving transfusion dependence in more than 70% patients in the real world."

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

Successful treatment of refractory cold agglutinin syndrome using fixed duration daratumumab, bortezomib and dexamethasone with a sutimlimab bridge. (PubMed, Haematologica) - "Not available."

Journal

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