Sustained improvements in patient-reported outcomes after long-term sutimlimab in patients with cold agglutinin disease: results from the CADENZA study open-label extension

Alexander Röth; Catherine M Broome; Wilma Barcellini; Bernd Jilma; Quentin A Hill; David Cella; Tor Henrik Anderson Tvedt; Masaki Yamaguchi; Irina Murakhovskaya; Michelle Lee; Frank Shafer; Marek Wardęcki; Deepthi Jayawardene; Ronnie Yoo; Jerome Msihid; Ilene C Weitz

doi:10.1016/j.eclinm.2024.102732

Sustained improvements in patient-reported outcomes after long-term sutimlimab in patients with cold agglutinin disease: results from the CADENZA study open-label extension

EClinicalMedicine. 2024 Jul 18:74:102732. doi: 10.1016/j.eclinm.2024.102732. eCollection 2024 Aug.

Authors

Alexander Röth¹, Catherine M Broome², Wilma Barcellini³, Bernd Jilma⁴, Quentin A Hill⁵, David Cella⁶, Tor Henrik Anderson Tvedt⁷, Masaki Yamaguchi⁸, Irina Murakhovskaya⁹, Michelle Lee¹⁰, Frank Shafer¹⁰, Marek Wardęcki¹¹, Deepthi Jayawardene¹², Ronnie Yoo¹², Jerome Msihid¹³, Ilene C Weitz¹⁴

Affiliations

¹ Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
² Division of Hematology, MedStar Georgetown University Hospital, Washington, DC, USA.
³ Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁴ Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
⁵ Leeds Teaching Hospitals NHS Trust, Leeds, UK.
⁶ Department of Medical Social Sciences, Center for Patient-Centered Outcomes, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
⁷ Section for Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
⁸ Ishikawa Prefectural Central Hospital, Japan.
⁹ Department of Hematology and Oncology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA.
¹⁰ Sanofi, Bridgewater, NJ, USA.
¹¹ Sanofi, Warsaw, Poland.
¹² Sanofi, Cambridge, MA, USA.
¹³ Sanofi, Gentilly, France.
¹⁴ Keck School of Medicine of USC, Los Angeles, CA, USA.

Abstract

Background: Cold agglutinin disease (CAD) is a rare subtype of autoimmune haemolytic anaemia characterised by classical complement pathway-mediated haemolysis, fatigue, and poor quality of life (QoL). Sutimlimab, a C1s inhibitor, rapidly halted haemolysis, and improved patient-reported outcomes (PROs) in patients with CAD in two phase 3 trials (CARDINAL and CADENZA). Here we report PROs from the CADENZA open-label extension (Part B).

Methods: The first patient was enrolled in CADENZA (NCT03347422) in March 2018 (Part A) and the last patient completed the study in December 2021 (Part B). All patients who completed the 26-week Part A were eligible to receive biweekly doses of sutimlimab in Part B for up to 1 year after the last patient completed Part A. PROs were assessed throughout Part B, until the last on-treatment visit with available assessment (LV), and after a 9-week washout.

Findings: In total, 32/39 patients completed Part B; median Part B treatment duration: 99 weeks. Patients switching from placebo to sutimlimab in Part B experienced rapid improvement in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score and other PROs. Sustained, clinically important improvements in FACIT-Fatigue were observed throughout Part B in patients who switched to sutimlimab and those continuing sutimlimab treatment (combined-group mean [SE] change from baseline at LV: 8.8 [2.1]). Similarly, the combined-group mean [SE] change for 12-Item Short Form Health Survey physical (4.9 [1.7]) and mental (4.0 [1.8]) component scores exceeded clinically important changes from baseline at LV. EuroQol visual analogue scale showed consistent and sustained increases from baseline with sutimlimab treatment. Following a 9-week washout, all PROs approached baseline values.

Interpretation: Continued inhibition of the classical complement pathway with sutimlimab results in meaningful long-term improvements in PROs (fatigue and QoL) in patients with CAD.

Funding: Sanofi.

Keywords: Cold agglutinin disease; Fatigue; Patient-reported outcomes; Quality of life; Sutimlimab.