Systematic Literature Review and Network Meta-Analysis of Crovalimab Compared With Eculizumab, Ravulizumab and Best Supportive Care in Paroxysmal Nocturnal Hemoglobinuria
Author(s)
Christian Bührer, PhD1, Elsbeth Frick, PhD2, Pablo Katz, PhD2, Xenia Studera, PhD2, Lori Yin, M.Sc.3.
1Evidence Lead, Roche, Basel, Switzerland, 2F. Hoffmann-La Roche Ltd, Basel, Switzerland, 3Hoffmann-La Roche Limited, Toronto, ON, Canada.
1Evidence Lead, Roche, Basel, Switzerland, 2F. Hoffmann-La Roche Ltd, Basel, Switzerland, 3Hoffmann-La Roche Limited, Toronto, ON, Canada.
Presentation Documents
OBJECTIVES: Crovalimab is a novel anti-C5 antibody for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). In the randomized, Phase III COMMODORE 2 (C5 inhibitor-naive) study, crovalimab showed non-inferior efficacy outcomes vs eculizumab. These findings were supported by results from the randomized, Phase III COMMODORE 1 (C5 inhibitor-pretreated) study. This research aims to investigate the relative effectiveness of crovalimab vs eculizumab, ravulizumab, and best supportive care (BSC) for patients with PNH.
METHODS: A systematic literature review was conducted to identify randomized clinical trials investigating complement inhibitors for patients with PNH. The main endpoints were the proportions of patients with transfusion avoidance (TA) and breakthrough hemolysis (BTH) as well as the change in FACIT-Fatigue score from baseline. Data from trials with C5 inhibitor-naive and pre-treated patients were pooled for the base case and analyzed separately for subgroup analyses. Five studies with relevant data were eligible, informing a Bayesian Network Meta-Analysis (NMA) to estimate the effectiveness of crovalimab vs eculizumab, ravulizumab and BSC. Mean differences and the probability of crovalimab being non-inferior were calculated using simulated data from random-effect (RE) models (base case) and fixed-effects (FE) models (subgroup analysis).
RESULTS: The probability of crovalimab being non-inferior to ravulizumab for TA and BTH was consistently >90% in the base case analysis. The respective probability of crovalimab being associated with a greater change in FACIT-Fatigue score vs ravulizumab was higher than 80%. Compared with eculizumab, change in FACIT-Fatigue score was statistically greater for crovalimab. BSC was consistently associated with worse outcomes compared with crovalimab. Results of subgroup and base case analyses were generally consistent.
CONCLUSIONS: NMA results indicated a high probability that crovalimab is associated with non-inferior clinical outcomes vs ravulizumab for C5 inhibitor-naive and pre-treated patients. Quality of life measured by FACIT-Fatigue score was numerically better vs ravulizumab and statistically better vs eculizumab.
METHODS: A systematic literature review was conducted to identify randomized clinical trials investigating complement inhibitors for patients with PNH. The main endpoints were the proportions of patients with transfusion avoidance (TA) and breakthrough hemolysis (BTH) as well as the change in FACIT-Fatigue score from baseline. Data from trials with C5 inhibitor-naive and pre-treated patients were pooled for the base case and analyzed separately for subgroup analyses. Five studies with relevant data were eligible, informing a Bayesian Network Meta-Analysis (NMA) to estimate the effectiveness of crovalimab vs eculizumab, ravulizumab and BSC. Mean differences and the probability of crovalimab being non-inferior were calculated using simulated data from random-effect (RE) models (base case) and fixed-effects (FE) models (subgroup analysis).
RESULTS: The probability of crovalimab being non-inferior to ravulizumab for TA and BTH was consistently >90% in the base case analysis. The respective probability of crovalimab being associated with a greater change in FACIT-Fatigue score vs ravulizumab was higher than 80%. Compared with eculizumab, change in FACIT-Fatigue score was statistically greater for crovalimab. BSC was consistently associated with worse outcomes compared with crovalimab. Results of subgroup and base case analyses were generally consistent.
CONCLUSIONS: NMA results indicated a high probability that crovalimab is associated with non-inferior clinical outcomes vs ravulizumab for C5 inhibitor-naive and pre-treated patients. Quality of life measured by FACIT-Fatigue score was numerically better vs ravulizumab and statistically better vs eculizumab.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO54
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Comparative Effectiveness or Efficacy
Disease
SDC: Rare & Orphan Diseases, SDC: Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)