FDA Approves Enjaymo™ (sutimlimab-jome), the First and Only Treatment for Cold Agglutinin Disease, Demonstrating Rapid Improvement in Hemolysis, Anemia, and Fatigue Within One Week

News on February 12, 2022 /BioValleyBIOON/ -- Sanofi recently announced that the U.S. Food and Drug Administration (FDA) has approved Enjaymo (sutimlimab-jome): for the treatment of adult patients with cold agglutinin disease (CAD), reducing the need for red blood cell transfusions due to hemolysis. Notably,Enjaymo is the first and only approved drug for the treatment of CAD, working by inhibiting red blood cell destruction (hemolysis).

CAD is a rare, serious, chronic,AutoimmuneHemolyticAnemiaA disease in which the complement system of the immune system mistakenly attacks healthy red blood cells in the body, leading to the rupture of red blood cells (hemolysis). Patients with CAD may experience chronic anemia, severe fatigue, acute hemolytic crisis, 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 active pharmaceutical ingredient of Enjaymo is sutimlimab, a first-in-class humanized monoclonal antibody specifically designed to selectively target and inhibit serine protease C1s in the C1 complex, which is the first step in activating the classical complement pathway of the immune system. The classical complement pathway is part of the innate immune system, and its activation is a central mechanism in CAD-related hemolysis. By targeting and inhibiting C1s, sutimlimab is believed to block the activation of the classical complement pathway, thereby preventing C1 activation-induced hemolysis in CAD.

Cold Agglutinin Disease - CAD (Image Source: medicine-science-and-more.com)

Sutimlimab targets the root cause of CAD hemolysis by selectively inhibiting complement C1s. Sutimlimab, with its novel mechanism of action and high target specificity, selectively inhibits the upstream classical complement pathway involved in the disease process while preserving the intact alternative complement pathway, lectin complement pathway, and their immune surveillance functions. Previously,FDASutimlimab has been granted Breakthrough Therapy Designation (BTD) and Orphan Drug Designation (ODD).

This approval is based on the results from Part A of the pivotal Phase 3 CARDINAL open-label single-arm study. Relevant data have been published in the international medical journal, The New England Journal of Medicine (NEJM). For more details, see the article:Sutimlimab in Cold Agglutinin Disease. This study evaluated the safety and efficacy of sutimlimab in treating adult patients with primary cold agglutinin disease (CAD) over 26 weeks.

The results showed,The study met both the primary and secondary endpoints, with sutimlimab demonstrating rapid and sustained inhibition of hemolysis mediated by the classical complement pathway (C1 activation-induced hemolysis, abnormal destruction of healthy red blood cells) within one week of treatment. It also improved anemia, reduced fatigue, and maintained consistent therapeutic effects throughout the study. Functional assays showed that the activity of the classical complement pathway was quickly suppressed, with increases in hemoglobin levels, decreases in bilirubin levels, and reduction in fatigue, all consistent with the inhibition of the classical complement pathway.

Sutimlimab - Mechanism of Action

CARDINAL is a 26-week, open-label, single-arm study enrolling CAD patients (n=24) with a recent history of transfusions. The study demonstrated that sutimlimab achieved the pre-specified primary composite efficacy endpoint, defined as the proportion of patients meeting all the following composite criteria: an increase in hemoglobin levels by ≥2 g/dL from baseline or reaching a hemoglobin level of ≥12 g/dL at the 26-week treatment evaluation time point, no transfusions between weeks 5 and 26, and no allowance for other CAD-related treatments. Specific data showed that: 54% (n=13) of patients met the composite endpoint criteria, 62.5% (n=15) achieved a hemoglobin level of ≥12 g/dL or an increase of at least 2 g/dL from baseline, and 71% (n=17) required no transfusions during weeks 5-26.

In addition, the trial showed that sutimlimab also met key secondary endpoints: demonstrating improvements in critical indicators of disease progression, including improvement in hemoglobin, normalization of bilirubin, and improvement in Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scores. The results showed an overall average increase in hemoglobin of 2.6 g/dL at the efficacy evaluation time point. By week 3, hemoglobin levels had increased on average by ≥2 g/dL from baseline. After week 3, the average hemoglobin level remained above 11 g/dL (with an average baseline level of 8.6 g/dL), indicating sustained efficacy during the remainder of the treatment period. The average total bilirubin was 55 μmol/L (2.7 times ULN) at baseline and decreased to 15 μmol/L (0.8 times ULN) at the efficacy evaluation time point. Clinically significant reductions in fatigue were observed as early as week 1 of treatment and were maintained throughout the study.

During the 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 (TEAE). The most commonAdverse ReactionsThe increase in blood pressure and infusion-related reactions. Seven patients (29.2%) experienced at least one treatment-emergent serious adverse event (TESAE), of which two patients (8.3%) had at least one TESAE caused by infection, and one patient died from an unrelated event (Liver Cancer). No cases of meningococcal infection were reported, and no patients developed systemicLupus ErythematosusAt the end of the 26-week treatment period in Part A of the CARDINAL study, eligible patients continued to receive sutimlimab for 24 months (Part B) to evaluate long-term safety and the durability of response. (Bioon.com)

Source of the original text:FDA approves Enjaymo™ (sutimlimab-jome), first treatment for use in patients with cold agglutinin disease