Real-World Safety Data Confirms Long-Term Tolerability of ENJAYMO in Cold Agglutinin Disease Patients
Key Insights
Recordati Rare Diseases presented updated real-world safety data from the CADENCE registry showing no new safety signals for ENJAYMO (sutimlimab) after an average treatment duration of more than two years in 63 patients with cold agglutinin disease (search).
The analysis revealed that 52.4% of patients experienced adverse events, with only 9.5% considered related to sutimlimab treatment, and one unexpected serious adverse event of chest pain/stable angina.
The safety findings from this multinational prospective registry were consistent with earlier clinical trial data, supporting the continued use of sutimlimab for treating hemolysis in adults with cold agglutinin disease (search).
Recordati Rare Diseases announced new real-world safety data for ENJAYMO (sutimlimab-jome (search)) at the 67th American Society of Hematology Annual Meeting, demonstrating the therapy's continued safety profile in patients with cold agglutinin disease (search) (CAD) after extended treatment periods. The data, derived from the CADENCE registry, represents the most comprehensive long-term safety analysis of sutimlimab treatment to date.
CADENCE Registry Findings
The updated analysis from the CADENCE registry examined safety data from 63 sutimlimab-treated patients enrolled across the United States, Japan, and Europe between December 12, 2019, and February 4, 2025. The cohort included 58 patients diagnosed with CAD, four with cold agglutinin syndrome (search) (CAS), and one with an unconfirmed diagnosis. The mean age of patients was 72.7 years, with 76.2% being female.
At the time of data analysis, patients had received sutimlimab for a median duration of 22.7 months and a mean duration of 25.1 months. This extended treatment period provides valuable insights into the long-term safety profile of the therapy.
Safety Profile Analysis
The safety analysis revealed that 159 adverse events were reported in 33 patients (52.4%) of the sutimlimab-treated cohort. Notably, only six patients (9.5%) experienced adverse events that investigators considered related to sutimlimab treatment. Of the 37 serious adverse events reported in 11 patients (17.5%), only one—chest pain/stable angina—was deemed an unexpected sutimlimab-related serious adverse event.
The registry documented one death in the cohort due to low right lung pneumonia, which investigators determined was unrelated to sutimlimab treatment. Adverse events of special interest included serious infections in three patients and arterial hypertension in two patients, though none of these were considered related to sutimlimab. Eight patients experienced non-serious acrocyanosis, with two cases considered possibly related to the treatment.
Clinical Significance
"The CADENCE registry comprises the world's largest dataset of treatment patterns and regimens, including a sutimlimab-treated cohort, in patients with cold agglutinin disease (search) and cold agglutinin syndrome (search), offering a unique, real-world view of how patients respond to long-term therapy," said lead investigator Catherine M. Broome, MD, Professor of Medicine and Director of Cellular Apheresis at the Lombardi Cancer Center at MedStar Georgetown University. "Our updated analysis of the sutimlimab cohort did not identify any new safety signals after an average treatment duration of more than two years. The safety findings were consistent with earlier clinical trial data in CAD."
About Cold Agglutinin Disease
Cold agglutinin disease (search) is a rare type of autoimmune hemolytic anemia (search) characterized as a low-grade lymphoproliferative disorder of the bone marrow. In CAD, autoantibodies bind to erythrocytes at temperatures ≤37°C, leading to complement-mediated hemolysis. The condition causes severe, debilitating fatigue and other clinical manifestations including dyspnea and tachycardia that significantly impact patients' quality of life. While the median age of onset is approximately 60 years, CAD has been diagnosed in patients as young as 30.
ENJAYMO Mechanism and Approvals
ENJAYMO is a humanized monoclonal antibody designed to specifically bind to complement protein component 1 (search), s (C1s (search)) subcomponents in the C1 complement complex, part of the classical complement pathway. By binding to C1s, the therapy inhibits activation of the classical complement pathway, preventing deposition of complement opsonins on red blood cells and resulting in inhibition of hemolysis.
The FDA approved ENJAYMO in February 2022 for treating hemolysis in adults with CAD. The Japanese Ministry of Health, Labor and Welfare granted approval in June 2022, followed by European Medicines Agency marketing authorization in November 2022. Both the FDA and EMA have designated ENJAYMO as an orphan drug.
Registry Limitations and Future Directions
Alessandro Albuquerque, MD, PhD, Chief Medical Officer and Vice President of Medical Affairs and Clinical Development at Recordati, commented, "The CADENCE registry data expand upon the real-world evidence base supporting the use of sutimlimab therapy for patients with cold agglutinin disease (search). Recordati remains committed to meeting the needs of individuals living with rare disorders, and we look forward to additional updates from the CADENCE registry as follow-up continues."
The researchers emphasized that CADENCE is an observational registry, and results should be interpreted with caution as they are descriptive in nature. ENJAYMO is not approved for treatment of cold agglutinin syndrome (search), and the safety and efficacy of sutimlimab has not been established in CAS patients.