2026 American Academy of Neurology Abstract Website

Luis Querol¹, Richard A. Lewis², Hans-Peter Hartung³, Pieter A. van Doorn⁴, Jie Lin⁵, Annie Dionne⁶, Shahram Attarian⁷, Erik Wallstroem⁸, Kristen Auwarter⁹, Yi Lu¹⁰, Miguel Alonso-Alonso⁸, Nazem Atassi⁸, Richard A. C. Hughes¹¹
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, ²Department of Neurology, Cedars 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, ⁵Department of Neurology and Rare Disease Center, Huashan Hospital, Fudan University, Shanghai, China, ⁶CHU de Quebec Universite Laval, Quebec, Canada, ⁷Neuromuscular Disease and ALS Reference Center, Timone University Hospital, Aix-Marseille University, CHU Timone, Marseille Cedex 05, France, ⁸Sanofi R&D, Neurology Development, Cambridge, MA, USA, ⁹Sanofi, USA, ¹⁰Sanofi R&D, Biostatistics and Programming, Cambridge, MA, USA, ¹¹UCL Queen Square Institute of Neurology, University College London, London, UK

Objective:

To report efficacy and safety of riliprubart at Week-76.

Background:

Riliprubart, a first-in-class humanized IgG4-monoclonal antibody, selectively inhibits activated-C1s in the classical-complement pathway and can be self-administrated subcutaneously via an auto-injector. Preliminary results from an ongoing Phase-2 trial of riliprubart in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP; NCT04658472) suggested encouraging clinical-benefits and safety-profile up to 48-weeks.

Design/Methods:

This open-label, Phase-2 trial evaluates riliprubart across three groups: Standard-of-care (SoC)-Treated, SoC-Refractory, and SoC-Naïve. Participants undergo 24-week treatment (Part-A), followed by an optional treatment-extension (Part-B: 52-weeks). Primary-endpoint (Part-A) is %-participants relapsing (SoC-Treated) or responding (SoC-Refractory/Naïve), defined as ≥1-point change in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) score. Part-B evaluates safety and efficacy-durability based on %-relapse-free participants (SoC-Treated) or with sustained-response (SoC-Refractory/Naïve), defined as no-increase in adjusted INCAT score ≥2-points at Week-76 relative to Week-24. Exploratory-endpoints include additional efficacy measures (INCAT, I-RODS, MRC-SS, grip-strength), change in total-complement, and plasma neurofilament-light chain (NfL) levels.

Results:

At Week-24, Part-A interim-analysis showed 87% (N=42/48) SoC-Treated participants improved/remained stable (improved: 52%; N=25/48) after directly switching from SoC to riliprubart. 50% (N=9/18) SoC-Refractory, and 75% (N=9/12) SoC-Naïve participants responded to riliprubart. As of April-2025, 74% (N=58/78) participants entered, and 83% (N=48/58) completed Part-B (ongoing:2% [1/58]; discontinued:16% [9/58]). In SoC-Treated group, at least 80% (32/40) participants who improved/remained stable after switching from SoC to riliprubart in Part-A continued to be relapse-free at Week-76. At least 78% (N=7/9) SoC-Refractory and 86% (N=6/7) SoC-Naïve participants who responded in Part-A had sustained-response. Riliprubart demonstrated sustained-reduction of complement activity, and 35% NfL reduction from baseline at Week-76. Updated full Part-B data up to Week-76 will be presented at meeting.

Conclusions:

Week-76 results suggest riliprubart may provide sustained clinical benefits in a broad spectrum of participants with CIDP, including those who experience failure/inadequate response/residual disability despite SoC therapy, supporting its development in Phase-3, and a potentially new treatment option.