Preliminary Efficacy and Safety Data from the Phase 2 Trial of Riliprubart (SAR445088), a Humanized Monoclonal Antibody Targeting Complement C1s, in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Luis Querol1, Richard Lewis2, Hans-Peter Hartung3, Pieter Van Doorn4, Erik Wallstroem5, Xiaodong Luo6, Miguel Alonso Alonso5, Nazem Atassi5, Richard Hughes7
1Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, 2Cedars Sinai Medical Center, 3Department of Neurology, Faculty of Medicine, Heinrich Heine University, 4Erasmus MC, University Medical Center, 5Sanofi R&D, Neurology Development, 6Sanofi R&D, Biostatistics and Programming, 7UCL Queen Square Institute of Neurology, University College London
Objective:
Report preliminary efficacy and safety results for riliprubart, a novel complement C1s-inhibitor, in people with CIDP.
Background:
Complement activation plays a role in CIDP pathogenesis. Riliprubart, a first-in-class humanized IgG4-monoclonal antibody, selectively inhibits activated C1s in the classical complement pathway and has a convenient subcutaneous route of administration. It may offer a new therapeutic option for people with CIDP, including cases refractory to standard therapies.
Design/Methods:
Phase 2, open-label trial (NCT04658472) evaluating riliprubart across three groups: Standard-of-Care (SOC)-Treated (immunoglobulin/corticosteroids), SOC-Refractory, and SOC-Naïve. Participants undergo a 24-week treatment (Part-A), followed by an optional 52-week treatment extension (Part-B). Primary endpoint is % participants relapsing (SOC-Treated) or responding (SOC-Refractory/Naïve), defined as ≥1-point change in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score in Part-A, and long-term safety and efficacy durability (Part-B). Secondary endpoints include additional efficacy measures (i.e., INCAT, I-RODS, MRC-SS, and grip-strength). Data are analyzed using Bayesian statistics based on predefined efficacy targets (based on historical data).
Results:
Part-A results from the pre-specified interim-analysis in May 2023 show that 88% SOC-Treated participants improved or remained stable after switching from SOC to riliprubart, and 44% (N=11/25) improved; 3 participants relapsed (12%, N=3/25) while 50% SOC-Refractory participants (N=9/18) responded to riliprubart. Clinically meaningful improvements were observed consistently across disability and impairment measures (i.e., INCAT, I-RODS, MRC-SS, and grip-strength). Plasma neurofilament light chain showed a trend-level reduction over time. 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 comorbidities. The most frequent TEAEs were headache, fatigue, and nasopharyngitis. Data for the SOC-Naïve group were unavailable during abstract development and will be presented at the AAN annual meeting.
Conclusions:
These proof-of-concept results demonstrate a favorable benefit:risk profile of riliprubart, which will be further investigated in Phase 3.