Positive results from the sutimlimab pivotal trial for people with cold agglutinin disease published in New England Journal of Medicine.- Sanofi

The New England Journal of Medicine (NEJM) published the final results of Part A of the pivotal Phase III CARDINAL open label, single-arm study evaluating the safety and efficacy of sutimlimab for 26 weeks in people with primary cold agglutinin disease (CAD). Sutimlimab, a first-in-class investigational C1s inhibitor from Sanofi, met the primary and secondary endpoints in the study and demonstrated sustained inhibition of classical complement pathway mediated hemolysis with improvements in anemia within one week of treatment. The NEJM publication included efficacy and safety results from Part A of the Phase III CARDINAL study, a 26-week, open label, single arm study of patients with CAD (n=24) who had a recent history of blood transfusions. The study demonstrated sutimlimab met its pre-specified primary composite endpoint of an increase in hemoglobin greater than 2 g/dL from baseline or reaching a hemoglobin level greater than 2 g/dL at the 26-week treatment assessment timepoint; the absence of transfusions from Weeks 5 to 26; and patients were not allowed to receive other CAD-related treatment. In the study, 54 percent (n=13) of patients met the composite endpoint criteria with 62.5 percent (n=15) of patients achieving a hemoglobin greater than 12 g/dL or an increase of at least 2 g/dL and 71 percent (n=17) of patients remaining transfusion-free after week 5 .Key secondary endpoints were also met and indicate improvements in hemoglobin and normalization of bilirubin. The study showed an overall mean increase in hemoglobin of 2.6 g/dL at treatment assessment timepoint. Hemoglobin improved with a mean increase from baseline of greater than 2 g/dL by week 3. Mean hemoglobin levels were maintained at >11 g/dL (from a mean baseline 8.6 g/dL) after week 3, demonstrating a sustained effect throughout the remainder of the treatment period. Mean total bilirubin was 55 umol/L (2.7-fold ULN) at baseline and 15 umol/L (0.8-fold ULN) at the treatment assessment time point. The study also measured the Functional Assessment of Chronic Illness Therapy-Fatigue Score. In the completed 26-week core treatment period (Part A) of the CARDINAL study, 22 of 24 patients (91.7%) experienced at least one treatment-emergent adverse event. The most common adverse events were increase in blood pressure and infusion-related reactions. Seven patients (29.2%) experienced at least one treatment-emergent serious adverse event (TESAE), including 2 patients (8.3%) that experienced at least one TESAE of infection and 1 death in a patient due to an unrelated event of hepatic cancer. There were no events of meningococcal infections reported, and no patients developed systemic lupus erythematosus. Following the completion of the Part A (26-week) treatment period of the CARDINAL study, eligible patients continue to receive sutimlimab in an on-going extension study for an additional 24 months (Part B) to evaluate the long-term safety and durability of response. See- "Sutimlimab in Cold Agglutinin Disease"-Alexander Röth, M.D., Wilma Barcellini, M.D., ., et al.-April 8, 2021 N Engl J Med 2021; 384:1323-1334. DOI: 10.1056/NEJMoa2027760.