The investigative monoclonal antibody may become the first therapy indicated for the rare autoimmune disease.
Alexander Roth, MD
Investigative therapy sutimlimab provided significant benefit for patients with cold agglutinin disease (CAD) across a series of symptomatic and patient-burden related outcomes, according to new data presented at the American Society of Hematology (ASH) 2019 Annual Meeting in Orlando.
In a phase 3 clinical trial assessing the novel monoclonal antibody in patients with the red blood cell-destroying autoimmune disease over 26 weeks of care, a team of investigators led by Alexander Roth, MD, found the drug resulted in improved patient hemoglobin levels, fewer blood transfusions, and significantly less fatigue.
Roth, of the University of Duisburg-Essen in Germany, and colleagues now believe they may have found the first treatment that could be indicated for CAD, which predominately affects older patients.
“I think we have finally turned the corner with research related to CAD, and now have the potential to offer a targeted therapy for these patients, pending health authority approvals,” Roth said in a statement.
Investigators enrolled 24 patients with an average age of 71 years old. All patients had evidenced, active CAD, including hemoglobin levels ≤10 g/dL, an above-average total bilirubin count, and at least 1 blood transfusion in the past 6 months.
Patients received sutimlimab intravenously for 26 weeks, with their symptoms being assessed at weeks 23, 25, and 26. Investigators assessed for a primary endpoint of composite hemoglobin increase of 2 or greater, or a total hemoglobin level of 12 or higher, plus the avoidance of blood transfusion from weeks 5-26.
Investigators also assessed for changes in bilirubin levels and patient quality of life, the latter via the FACIT-Fatigue score.
At trial’s end, 22 patients had completed treatment. Patients’ hemoglobin levels improved rapidly following the first dose of sutimlimab, indicating an achieved primary endpoint. Most patients reported a hemoglobin level above 11 g/dL by week 3, and retained normalized total bilirubin.
Quality of life scores improved in alignment with hemoglobin improvement, and was maintained through 26 weeks. Though nearly all (92%) patients reported at least 1 adverse event during the study, most were related to invasive procedures or pre-existing medical conditions unrelated to sutimlimab.
Non-serious adverse events related to the therapy included swelling, raised blood pressure, and runny nose. All 22 patients to complete the trial elected to participate in a continued second phase which will assess the long-term outcomes of sutimlimab.
As a monoclonal antibody, sutimlimab is designed to block C1s proteins from activating the part of the immune system that is overactive in people with CAD—the classical complement pathway.
Roth and colleagues expressed thrill over reaching their several clinical efficacy outcome measures, and the durability of response from classical complement pathway inhibition.
“This really illustrates that targeting C1s in the classical complement pathway can have a meaningful impact on hemolysis, anemia, and fatigue, which are important clinical features of CAD,” Roth said.