Abstract Topic: 28. Enzymopathies, membranopathies and other anemias
Background: Sutimlimab (SUT) is a humanized monoclonal antibody approved for patients with cold agglutinin disease (CAD), a rare chronic autoimmune hemolytic anemia. Through selective C1s inhibition, SUT prevents classical complement pathway-mediated hemolysis, characteristic of CAD. In Part A of CADENZA (NCT03347422), a randomized, double-blind, placebo-controlled Phase 3 study, SUT treatment resulted in rapid and sustained improvements in hemoglobin (Hb), hemolytic markers and quality of life (QoL).
Aims: To report long-term safety and efficacy findings of SUT treatment in patients (pts) with CAD, from CADENZA Part B, the open-label extension.
Methods: In Part A (26 weeks), pts with CAD, without a history of recent blood transfusion, received SUT or placebo (PBO) on Days 0 and 7, then biweekly. Pts completing Part A could enter Part B and receive biweekly SUT for ≥1 year after the last pt completed Part A. Efficacy endpoints included change from baseline (BL) in Hb, hemolytic markers, and FACIT-Fatigue score. The proportion of subjects achieving pre-defined Hb increases and normalized bilirubin was analyzed. Safety data were recorded throughout the study; treatment emergent adverse events (TEAEs) and serious TEAEs (TESAEs).
Results: In total, 39 pts completed Part A and entered Part B, and 32 (82.1%) completed Part B. At the end of Part A, in SUT and PBO groups, respectively, mean (SE) Hb was 11.51 (0.40) g/dL and 9.43 (0.40) g/dL (Figure), Hb levels ≥11 g/dL were observed in 73.7% and 20.0% of pts, and change from BL in Hb ≥1.5 g/L was seen in 84.2% and 15.0% of pts (Table). In Part B, improvements in Hb were sustained in the SUT group and the ex-PBO group saw rapid, comparable increases in Hb upon initiation of SUT. At Week 79 (Part B), in the SUT-only and ex-PBO groups, respectively, mean (SE) Hb levels were 11.86 (0.54) g/dL and 11.76 (0.58) g/dL, Hb levels ≥11 g/dL were observed in 76.9% and 66.7% of pts, and change from BL in Hb ≥1.5 g/L was seen in 69.2% and 73.3% of pts (Table). Mean total bilirubin was normalized (≤20.5 μmol/L) at the end of Part A in 88.2% of pts with SUT, versus 22.2% with PBO. In Part B, Week 79, bilirubin normalization was observed in 83.3% and 80.0% of SUT only and ex-PBO pts, respectively (Table). Further efficacy data are shown in the table. Improvements in mean [SE] FACIT-Fatigue scores (BL: 32.96 [1.79]) observed in Part A were sustained in Part B in the SUT-only group (44.31 [2.19] at Week 87); the mean FACIT-Fatigue score increased to comparable levels in the ex-PBO group (41.40 [2.71] at Week 87). In Part B, 36 (92.3%) pts experienced ≥1 TEAE. A total of 11 TESAEs were experienced by 7 (17.9%) pts; one TESAE of hypertension was assessed as related to SUT by the investigator. Thromboembolic events were observed in 2 (5.1%) pts (transient ischemic attack [n=1]; deep vein thrombosis [n=1]); both events occurred in pts with underlying risk factors for thromboembolism and were assessed as non-serious and unrelated to SUT by the Investigator. One TESAE of infection (urinary tract infection Grade ≥3) was reported. No meningococcal infections, serious events of hypersensitivity, anaphylaxis or systemic lupus erythematosus were reported. One pt with a history of tobacco use (received PBO in Part A) experienced a TESAE of squamous cell carcinoma of the lung with fatal outcome. SUT was withdrawn due to this TESAE prior to death.
Summary/Conclusion: Long-term SUT treatment was well-tolerated, and was associated with sustained efficacy, with improvements in anemia, hemolysis and QoL.
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Keywords: Autoimmune hemolytic anemia (AIHA)