Sustained sutimlimab response for 3 years in patients with cold agglutinin disease: A phase I, open‐label, extension trial

Abstract

Cold agglutinin disease (CAD) is a rare autoimmune haemolytic anaemia (AIHA), which leads to fatigue and acrocyanosis. [1][2][3][4] Until recently, treatment of CAD was mainly based on reduction of the B-cell clone by rituximab or chemo-immunotherapy. While rituximab has a slow onset of action and variable efficacy with frequent relapses, 2 chemo-immunotherapy may be accompanied by pronounced toxicity. 5 Patients may still remain transfusion-dependent, which may lead to alloimmunisation or iron overload. 6 Sutimlimab, a monoclonal antibody targeting the C1s protein of the classical complement pathway, effectively reduced haemolysis, increased haemoglobin levels and reduced fatigue in prior studies. [7][8][9] In this open-label trial, we evaluated the safety and efficacy of long-term sutimlimab in four patients with CAD. The protocol was approved by the Ethics Committee of the Medical University of Vienna and the trial was conducted according to the principles set forth in the Declaration of Helsinki. The trial was conducted between December 2017 and March 2021 at the Medical University of Vienna. Following the first-in-human trial 10 and participation in a named patient programme, 9 four patients with CAD resumed treatment with sutimlimab every 2 weeks as

Sustained inhibition of complement C1s with sutimlimab over 2 years in patients with cold agglutinin disease

“…Sutimlimab is a humanized monoclonal antibody that prevents CP activation by targeting C1s; the alternative and lectin pathways of complement are left intact 15,16 . Sutimlimab's safety and efficacy for the treatment of patients with CAD have been demonstrated in a Phase 1b trial, subsequent extensions, and two pivotal Phase 3 studies 16–20 . In Part A of the open‐label, single‐arm, CARDINAL study of sutimlimab in patients with CAD and a recent history of transfusion, sutimlimab rapidly halted hemolysis, improved hemoglobin (Hb) levels, and reduced fatigue over 26 weeks 15 .…”

“…15,16 Sutimlimab's safety and efficacy for the treatment of patients with CAD have been demonstrated in a Phase 1b trial, subsequent extensions, and two pivotal Phase 3 studies. [16][17][18][19][20] In Part A of the open-label, single-arm, CARDINAL study of sutimlimab in patients with CAD and a recent history of transfusion, sutimlimab rapidly halted hemolysis, improved hemoglobin (Hb) levels, and reduced fatigue over 26 weeks. 15 In Part A of the randomized, double-blind, placebo-controlled, CADENZA study of sutimlimab in patients with CAD with no recent history of transfusion, sutimlimab, but not placebo, led to improvements in mean Hb levels and markers of hemolysis, and clinically meaningful improvements in fatigue that were sustained over 26 weeks.…”

Sutimlimab for the Treatment of Cold Agglutinin Disease

“… 44 Another small prospective study aimed to determine response duration in 4 patients who already had achieved remission on sutimlimab. 47 Treatment was discontinued for drug-unrelated reasons in 1 patient, but 3 patients continued for a mean duration of 52 months, including previous sutimlimab therapy. Sustained effects on Hb and bilirubin levels were observed throughout the study.…”

“…In a follow‐up study of 6 responders who had discontinued sutimlimab, all patients had an immediate relapse of hemolytic anemia after discontinuation, but complement inhibition and control of hemolysis were rapidly restored on retreatment 44 . Another small prospective study aimed to determine response duration in 4 patients who already had achieved remission on sutimlimab 47 . Treatment was discontinued for drug‐unrelated reasons in 1 patient, but 3 patients continued for a mean duration of 52 months, including previous sutimlimab therapy.…”

Sutimlimab: A Complement C1s Inhibitor for the Management of Cold Agglutinin Disease–Associated Hemolysis

“…Following the completion of this first-in-human phase I trial, 4 patients continued to receive sutimlimab every 2 weeks as part of an open-label, extension phase of this trial. 14 Each patient had a sutimlimab washout of at least 6 weeks following the transition to the extension phase of the trial. Treatment duration for these patients in the study ranged from 13 to 39 months.…”