Rare Daily Staff

Sanofi at the annual meeting of the American Society of Hematology in Orlando, Florida

presented said a pivotal phase 3 open-label, single-arm trial evaluating the safety and efficacy of sutimlimab in people with primary cold agglutinin disease met its primary and secondary endpoints.

Cold agglutinin disease (CAD) is a serious, chronic rare blood disease in which a part of the body’s immune system called the complement system mistakenly attacks a person’s own healthy red blood cells. People with CAD suffer from chronic anemia, debilitating fatigue, acute hemolytic crisis, and a poor quality of life. They also have an increased risk of thromboembolic events and early mortality. CAD occurs in approximately 16 people per million, including an estimated 12,000 people in the United States, Europe and Japan.

“Cold agglutinin disease can be a debilitating condition, with many patients suffering from crippling fatigue and generally experiencing a poor quality of life,” said Alexander Röth of the Department of Hematology at University Hospital at the University of Duisburg-Essen, Germany and principal investigator and presenting author. “These positive data from the phase 3 CARDINAL study provide clinically significant evidence that sutimlimab, by inhibiting hemolysis and improving anemia, has the potential to be an important new treatment for CAD and make a meaningful impact on patients’ lives.”

Sutimlimab is an experimental, first-in-class humanized monoclonal antibody that has been specifically designed to target C1s, a serine protease within the C1-complex, which is the first step in activating the classical complement pathway of the immune system. Activation of the classical complement pathway is the central mechanism of hemolysis in CAD and blocking it may potentially halt the CAD disease process. With a novel mechanism of action and high target specificity, sutimlimab is designed to selectively inhibit disease processes upstream in the classical complement pathway while leaving intact the alternative and lectin complement pathways and their immune surveillance functions.

The CARDINAL trial is a pivotal, open-label, single-arm study to assess the efficacy and safety of sutimlimab in adult patients with primary CAD who received a recent blood transfusion. The phase 3 trial enrolled 24 patients (mean age of 71.3 years) who received at least one weight-based dose of sutimlimab via intravenous infusion on Day 0, Day 7 and then once every other week up to Week 26.

Almost two thirds of patients had received one or more targeted therapies over the past five years. Two patients withdrew from the study early for reasons unrelated to study drug. All of the other 22 patients who completed Part A of the study elected to continue sutimlimab in Part B, an ongoing safety and durability of response extension study.

The primary efficacy outcome was a responder rate based on a composite of an increase in hemoglobin ≥2 g/dL from baseline or reaching a hemoglobin level ≥12 g/dL at the 26-week treatment assessment time point and the absence of transfusions from weeks 5 to 26. Patients were not allowed to receive other CAD-related treatments. The secondary efficacy measures assessed improvement in key indicators of the disease process: hemoglobin, bilirubin (a measure of red blood cell destruction in CAD), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score (a quality of life measure of fatigue), lactate dehydrogenase (LDH), and transfusion usage.

The pre-specified primary endpoint was met. More than half the patients (n=13) met the composite endpoint criteria, with 62.5 percent (n=15) of patients achieving a hemoglobin ≥ 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.

The study showed an overall mean increase in hemoglobin of 2.6 g/dL at treatment assessment timepoint, and 83 percent (n=20) of the 24 patients enrolled achieved a clinically significant mean hemoglobin improvement of ≥1 g/dL.

Mean FACIT-Fatigue score demonstrated a clinically meaningful improvement in fatigue by week 1 of treatment with an increase of 7.2 points. The overall mean FACIT-Fatigue score increase from baseline at the 26-week treatment assessment timepoint was 10.9 points.

Almost all the patients (n=22) experienced at least one treatment-emergent adverse event with sevent patients experiencing a treatment-emergent serious adverse event that the investigator assessed as not related to sutimlimab. Two patients experienced infection, again assessed as not related to the treatment and no patients discontinued the therapy due to infection.

“CAD is a disease in which the immune system attacks red blood cells and causes a cascade of symptoms for patients. In our study, sutimlimab achieved clinically meaningful results by impacting the central mechanism of CAD, bringing about marked improvements in patients’ hemolysis, anemia and fatigue,” said John Reed, global head of R&D at Sanofi. “We believe [it] has the potential to change the treatment paradigm for CAD.”

Sanofi plans to submit results from this trial to regulatory authorities, starting with the U.S. Food and Drug Administration in the near future. Sutimlimab has been granted Breakthrough Therapy designation by the FDA and has Orphan Drug status in the United States, European Union, and Japan.

Photo: John Reed, global head of R&D at Sanofi

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