Sanofi's First-in-Class C1s Inhibitor Sutimlimab Receives Complete Response Letter from FDA for Cold Agglutinin Disease

November 18, 2020 News /Bio ValleyBIOON/ -- Sanofi recently announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the Biologics License Application (BLA) for sutimlimab, a monoclonal antibody indicated for the treatment of hemolysis in adult patients with primary cold agglutinin disease (CAD). Sutimlimab targets the underlying cause of hemolysis in CAD by selectively inhibiting complement C1s.

In the CRL, the FDA noted that certain deficiencies were identified during the Pre-license Inspection (PLI) of the third-party facility responsible for manufacturing. No clinical or safety deficiencies related to the application were found in the CRL. The deficiencies mentioned in the CRL must be satisfactorily addressed by the third-party manufacturer before the BLA can be approved. Sanofi will work withFDAMaintain close contact with third-party manufacturers to facilitate timely resolution of issues.

In May this year, the FDA accepted the BLA for sutimlimab and granted it priority review. If approved, sutimlimab will become the first and only drug for treating CAD hemolysis. Previously,FDASutimlimab has been granted Breakthrough Therapy Designation (BTD) and Orphan Drug Designation (ODD).

CAD is a rare, severe, chronic,AutoimmunityHemolyticAnemiaCold Agglutinin Disease (CAD) is a condition in which the complement system of the immune system mistakenly attacks healthy red blood cells, causing them to rupture (hemolysis). Patients with CAD may experience chronic anemia, severe fatigue, acute hemolytic crises, and other potential complications, including an increased risk of thromboembolic events and premature death. It is estimated that there are approximately 5,000 patients with CAD in the United States.

The submission of the Biologics License Application (BLA) for sutimlimab was based on the results from Part A of the pivotal, open-label, single-arm Phase III CARDINAL study conducted in patients with primary cold agglutinin disease (CAD) (n=24). These data were presented at the 61st American Society of Hematology (ASH) Annual Meeting in 2019 and confirmed that sutimlimab met the primary composite efficacy endpoint, defined as the proportion of patients achieving all of the following criteria: an increase in hemoglobin level of ≥2 g/dL from baseline or attainment of a hemoglobin level ≥12 g/dL (based on the mean values at weeks 23, 25, and 26), and no transfusions during weeks 5–26. Furthermore, the trial demonstrated that sutimlimab also met secondary endpoints, showing improvements in key indicators of disease progression, including increased hemoglobin levels, normalization of bilirubin, and improved scores on the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale.

Sutimlimab is a potential first-in-class, investigational, humanized monoclonal antibody specifically designed to selectively target and inhibit C1s, the serine protease within the C1 complex, which constitutes the initial step in the activation of the classical complement pathway of the immune system. The classical complement pathway is a component of the innate immune system, and its activation represents the central mechanism underlying hemolysis in cold agglutinin disease (CAD). By selectively inhibiting C1s, sutimlimab is believed to block the activation of the classical complement pathway, thereby preventing C1-mediated hemolysis in CAD.

Sutimlimab features a novel mechanism of action and high target specificity, selectively inhibiting the upstream classical complement pathway during the disease process while preserving the intact alternative and lectin complement pathways and their immune surveillance functions.

Currently, Sanofi is evaluating sutimlimab in patients with cold agglutinin disease (CAD) who have not received recent transfusions in the Phase III CADENZA trial, and the company is also investigating sutimlimab for the treatment of patients with immune thrombocytopenia (ITP). (Bioon.com)

Original Source:FDA issues Complete Response Letter for sutimlimab, an investigational treatment for hemolysis in adults with cold agglutinin disease