SUTIMLIMAB, A COMPLEMENT C1S INHIBITOR, IMPROVES QUALITY OF LIFE IN PATIENTS WITH COLD AGGLUTININ DISEASE: PATIENT-REPORTED OUTCOMES RESULTS OF THE PHASE 3 CARDINAL STUDY
Author(s): ,
Alexander Röth
Affiliations:
Department of Hematology, West German Cancer Center, University Hospital Essen,University of Duisburg-Essen,Essen,Germany
,
Wilma Barcellini
Affiliations:
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico,Milan,Italy
,
Tor Henrik Anderson Tvedt
Affiliations:
Section for Hematology, Department of Medicine,Haukeland University Hospital,Bergen,Norway
,
Yoshitaka Miyakawa
Affiliations:
Thrombosis and Hemostasis Center,Saitama Medical University Hospital,Saitama,Japan
,
David J. Kuter
Affiliations:
Division of Hematology,Massachusetts General Hospital, Harvard Medical School,Boston, MA,United States
,
William Hobbs
Affiliations:
Sanofi,Waltham, MA,United States
,
Jun Su
Affiliations:
Sanofi,Cambridge, MA,United States
,
Xiaoyu Jiang
Affiliations:
Sanofi,Waltham, MA,United States
,
Jaime Morales Arias
Affiliations:
Sanofi,Cambridge, MA,United States
Ilene C. Weitz
Affiliations:
Jane Anne Nohl Division of Hematology, Department of Medicine,University of Southern California – Keck School of Medicine,Los Angeles, CA,United States
EHA Library. Röth A. 06/12/20; 295152; S333
Alexander Röth
Alexander Röth
Contributions
Abstract

Abstract: S333

Type: Oral Presentation

Session title: Integrating the patient's voice in hematology

Background
Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia characterized by activation of the classical complement pathway (CP) and extravascular hemolysis, resulting in a variety of symptoms, including profound fatigue, that may lead to a reduced quality of life (QoL). However, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and other QoL measures have not been previously evaluated in CAD. Sutimlimab (formerly BIVV009) is a first-in-class humanized monoclonal anti-C1s antibody that selectively inhibits the C1 complex of complement, preventing CP activation. It has recently been shown to stop hemolysis and significantly improve anemia in CAD.

Aims
Describe the effect of sutimlimab on patient-reported outcomes (PRO) as a measure of QoL, as assessed in Part A of the Phase 3 Cardinal study (NCT03347396).

Methods
Cardinal is an open-label, single-arm study in patients with CAD. Part A evaluated the efficacy and safety of sutimlimab over 26 weeks. Patients with primary CAD and ≥1 blood transfusion in the prior 6 months were enrolled. Informed consent was provided. Sutimlimab was administered intravenously on Days 0 and 7, and biweekly thereafter. Patients weighing <75 kg or ≥75 kg received a 6.5 g or 7.5 g dose, respectively. Mean change from baseline in fatigue was assessed as a secondary endpoint using the FACIT-F scale at the treatment assessment time point (TAT; defined as the average of the values from Weeks 23, 25, and 26). Mean change from baseline for exploratory endpoints of QoL was assessed using the 5-level EuroQol 5 dimensions questionnaire (EQ-5D-5L) and the 12-Item Short Form Health Survey (SF-12). Results were reported using descriptive statistics.

Results
Patients with CAD in this study were characterized by abnormal baseline QoL measures consistent with conditions such as cancer and autoimmune disorders and demonstrated clinically meaningful improvements across all PROs measured after treatment with sutimlimab. Of 24 patients enrolled, 17 had evaluable FACIT-F values at the TAT. Improvements in FACIT-F score were observed by Week 1 and were maintained through Week 26. Mean (standard deviation [SD]) FACIT-F scores increased from 32.5 (10.6) at baseline (a score indicative of severe fatigue) to 44.3 (6.5) at the TAT, with an estimated mean (standard error) FACIT-F score increase of 10.9 (1.4). Clinically meaningful FACIT-F improvements (≥3-point increases) were achieved in ≥75% of patients (interquartile range: 5.0–15.5 points). Among the 16 patients evaluable for EQ-5D-5L, the mean (SD) increases in index and visual analog scale scores from baseline to Week 26 were 0.074 (0.185) and 16.8 (16.9), respectively. Mobility and usual activities domains had the greatest improvements. The mean (SD) increases in SF-12 physical and mental component scores from baseline to Week 26 were 5.37 (7.60) and 4.37 (10.02) points (n=16), respectively. Improvements in all these QoL measures correlated with resolution of hemolysis, near-complete inhibition of CP activity, and rapid normalization of complement C4 (Figure 1A and 1B).

Conclusion
The Phase 3 Cardinal study demonstrated that, in addition to the degree of anemia, CP activation with subsequent hemolysis plays a critical role as a driver of fatigue symptoms and poor QoL in patients with CAD. Treatment with sutimlimab, an inhibitor of complement C1s, resulted in rapid, clinically meaningful improvements in all PRO measures evaluated, further supporting the effectiveness of targeting the CP in the management of patients with this condition.

Session topic: 35. Quality of life, palliative & supportive care, ethics and health economics

Keyword(s): Autoimmune hemolytic anemia (AIHA), Complement, Phase III, Quality of life

Abstract: S333

Type: Oral Presentation

Session title: Integrating the patient's voice in hematology

Background
Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia characterized by activation of the classical complement pathway (CP) and extravascular hemolysis, resulting in a variety of symptoms, including profound fatigue, that may lead to a reduced quality of life (QoL). However, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and other QoL measures have not been previously evaluated in CAD. Sutimlimab (formerly BIVV009) is a first-in-class humanized monoclonal anti-C1s antibody that selectively inhibits the C1 complex of complement, preventing CP activation. It has recently been shown to stop hemolysis and significantly improve anemia in CAD.

Aims
Describe the effect of sutimlimab on patient-reported outcomes (PRO) as a measure of QoL, as assessed in Part A of the Phase 3 Cardinal study (NCT03347396).

Methods
Cardinal is an open-label, single-arm study in patients with CAD. Part A evaluated the efficacy and safety of sutimlimab over 26 weeks. Patients with primary CAD and ≥1 blood transfusion in the prior 6 months were enrolled. Informed consent was provided. Sutimlimab was administered intravenously on Days 0 and 7, and biweekly thereafter. Patients weighing <75 kg or ≥75 kg received a 6.5 g or 7.5 g dose, respectively. Mean change from baseline in fatigue was assessed as a secondary endpoint using the FACIT-F scale at the treatment assessment time point (TAT; defined as the average of the values from Weeks 23, 25, and 26). Mean change from baseline for exploratory endpoints of QoL was assessed using the 5-level EuroQol 5 dimensions questionnaire (EQ-5D-5L) and the 12-Item Short Form Health Survey (SF-12). Results were reported using descriptive statistics.

Results
Patients with CAD in this study were characterized by abnormal baseline QoL measures consistent with conditions such as cancer and autoimmune disorders and demonstrated clinically meaningful improvements across all PROs measured after treatment with sutimlimab. Of 24 patients enrolled, 17 had evaluable FACIT-F values at the TAT. Improvements in FACIT-F score were observed by Week 1 and were maintained through Week 26. Mean (standard deviation [SD]) FACIT-F scores increased from 32.5 (10.6) at baseline (a score indicative of severe fatigue) to 44.3 (6.5) at the TAT, with an estimated mean (standard error) FACIT-F score increase of 10.9 (1.4). Clinically meaningful FACIT-F improvements (≥3-point increases) were achieved in ≥75% of patients (interquartile range: 5.0–15.5 points). Among the 16 patients evaluable for EQ-5D-5L, the mean (SD) increases in index and visual analog scale scores from baseline to Week 26 were 0.074 (0.185) and 16.8 (16.9), respectively. Mobility and usual activities domains had the greatest improvements. The mean (SD) increases in SF-12 physical and mental component scores from baseline to Week 26 were 5.37 (7.60) and 4.37 (10.02) points (n=16), respectively. Improvements in all these QoL measures correlated with resolution of hemolysis, near-complete inhibition of CP activity, and rapid normalization of complement C4 (Figure 1A and 1B).

Conclusion
The Phase 3 Cardinal study demonstrated that, in addition to the degree of anemia, CP activation with subsequent hemolysis plays a critical role as a driver of fatigue symptoms and poor QoL in patients with CAD. Treatment with sutimlimab, an inhibitor of complement C1s, resulted in rapid, clinically meaningful improvements in all PRO measures evaluated, further supporting the effectiveness of targeting the CP in the management of patients with this condition.

Session topic: 35. Quality of life, palliative & supportive care, ethics and health economics

Keyword(s): Autoimmune hemolytic anemia (AIHA), Complement, Phase III, Quality of life

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies