Phase 2 Efficacy and Safety of Riliprubart, a C1s-Complement Inhibitor, in Chronic Inflammatory Demyelinating Polyneuropathy
Luis Querol1, Richard A. Lewis2, Hans-Peter Hartung3, Pieter A. van Doorn4, Erik Wallstroem5, Kristen Auwarter6, Xiaodong Luo7, Miguel Alonso-Alonso5, Nazem Atassi5, Richard A. C. Hughes8
1Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Madrid, Spain, 2Cedars Sinai Medical Center, Los Angeles, CA, USA, 3Department of Neurology, Faculty of Medicine, Heinrich-Heine-University, Düsseldorf, Germany; Brain and Mind Center, University of Sydney, Sydney, NSW, Australia; Department of Neurology, Medical University of Vienna, Vienna, Austria; Department of Neurology, Palacky University Olomouc, Olomouc, The Czech Republic, 4Erasmus MC, University Medical Center, Rotterdam, The Netherlands, 5Sanofi R&D, Neurology Development, Cambridge, MA, USA, 6Sanofi, USA, 7Sanofi R&D, Biostatistics and Programming, Bridgewater, NJ, USA, 8UCL Queen Square Institute of Neurology, University College London, London, UK
Objective:
To report efficacy and safety results of riliprubart in chronic inflammatory demyelinating polyneuropathy (CIDP).
Background:
Riliprubart, a first-in-class humanized IgG4-monoclonal antibody, selectively inhibits activated-C1s within the classical complement pathway.
Design/Methods:
Global, multicenter, Phase-2, open-label trial (NCT04658472) evaluating riliprubart across three subgroups: Standard-of-care (SOC)-Treated (immunoglobulins/corticosteroids), SOC-Refractory, and SOC-Naïve. Participants undergo 24-week treatment (Part-A), followed by optional 52-week treatment-extension (Part-B). Part-A primary-endpoint for SOC-Treated is %-participants with relapse (≥1-point increase in adjusted Inflammatory Neuropathy Cause and Treatment [INCAT] disability score) after switching from SOC to riliprubart. For SOC-Refractory and SOC-Naïve, the primary-endpoint is %-participants with response (≥1-point decrease in adjusted INCAT score) from baseline up to 24-weeks. Part-B evaluates efficacy durability based on percentage of relapse-free participants (SOC-Treated) or those with sustained-response (SOC-Refractory/Naïve). Exploratory endpoints include additional efficacy measures (INCAT, I-RODS, MRC-SS, grip-strength), change in total complement (CH50), and plasma neurofilament-light chain (NfL). Safety is also evaluated.
Results:
As of May-2023, Part-A results from pre-specified interim-analysis show that 88% (N=22/25) SOC-Treated participants improved or remained stable (44% [N=11/25] improved) after switching from SOC to riliprubart, and 12% relapsed (N=3/25). For SOC-refractory participants, 50% (N=9/18) responded to riliprubart. Clinically meaningful improvements were observed across all secondary-efficacy measures. Sustained inhibition of complement activity and reduction in NfL levels were observed with riliprubart across all cohorts. Treatment-emergent adverse events (TEAEs) occurred in 60% (N=15/25) and 72% (N=13/18) of SOC-Treated and SOC-Refractory participants, respectively. Two deaths were reported in participants with significant medical comorbidities aside from CIDP. Most frequent TEAEs were headache, fatigue, and nasopharyngitis. Available Part-A and Part-B data for all subgroups will be presented at the meeting.
Conclusions:
These preliminary results support riliprubart’s proof-of-concept in CIDP, with a favorable benefit:risk profile, supporting further investigation as a potential new therapy for people with CIDP who experienced failure/inadequate response to SOC treatments and those with residual disability despite maintenance treatment.
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