Abstract Details

Title Safety and Efficacy of Riliprubart, an Activated C1s-complement Inhibitor in CIDP: 76-week Phase Two Trial Results

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S2 - Updates on Motor Neuron and Peripheral Nerve Disorders (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

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.

Authors/Disclosures
Richard A. Lewis, MD, FAAN (Cedars-Sinai Medical Center) PRESENTER	Dr. Lewis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Lewis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CSL Behring. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Grifols. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Takeda. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Nuvig. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Dianthus. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medscape. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Annexon. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Immunovant. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BioCryst. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NervoSave. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Annexon. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TGTX. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boehringer-Ingleheim. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intellia. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cartesian. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for CME Outfitters. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PeerVision. Dr. Lewis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Up to Date. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boehringer Ingelheim. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Lewis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Intellia. Dr. Lewis has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Shernoff et al. Dr. Lewis has received publishing royalties from a publication relating to health care.
Luis Querol, MD, PhD (Hospital de la Santa Creu i Sant Pau)	Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring. The institution of Dr. Querol has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. Dr. Querol has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ArgenX. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Annexon. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avilar. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocryst. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KPL. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lycia. The institution of Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Querol has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Querol has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Querol has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. The institution of Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ArgenX. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Grifols. The institution of Dr. Querol has received research support from GBS-CIDP Foundation International. The institution of Dr. Querol has received research support from Grifols. The institution of Dr. Querol has received research support from ISCIII. The institution of Dr. Querol has received research support from CIBERER. The institution of Dr. Querol has received research support from UCB. The institution of Dr. Querol has received research support from ArgenX.
Hans-Peter Hartung, MD, FAAN (Heinrich Heine University Medical Faculty)	Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology.
Pieter Van Doorn, MD (Erasmus University Medical Center)	The institution of Dr. Van Doorn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. The institution of Dr. Van Doorn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hansa. The institution of Dr. Van Doorn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Van Doorn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Octapharma. The institution of Dr. Van Doorn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. The institution of Dr. Van Doorn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Grifols. The institution of Dr. Van Doorn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Octapharma. The institution of Dr. Van Doorn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Van Doorn has received publishing royalties from a publication relating to health care.
Jie Lin	No disclosure on file
Annie Dionne, MD (CHU De Quebec Hopital Enfant-Jesus)	Dr. Dionne has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Dionne has received research support from Sanofi.
Shahram Attarian, MD, PhD (CHU La Timone Aix Marseille University)	Prof. Attarian has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SANOFI, Pfizer LFB, Alnylam Biogen Argenx, UCB Alexion, Astrazenica, Amicus, Janssen, Novartis, Roche. Prof. Attarian has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for SANOFI, Biogen,Alnylam, Argenx, USB, Alexion Astrazenica, Janssen, Roche, Amgen. The institution of Prof. Attarian has received research support from National Institut of Health .
Erik Wallstroem, MD, PhD (Sanofi)	Dr. Wallstroem has received personal compensation for serving as an employee of Sanofi. Dr. Wallstroem has stock in Sanofi. Dr. Wallstroem has received intellectual property interests from a discovery or technology relating to health care.
Kristen Auwarter, MD	Dr. Auwarter has received personal compensation for serving as an employee of Sanofi. An immediate family member of Dr. Auwarter has received personal compensation for serving as an employee of Medtronic. Dr. Auwarter has stock in Sanofi.
Qiang Lu, MD	Dr. Lu has nothing to disclose.
Miguel Alonso Alonso (Sanofi)	Miguel Alonso Alonso has received personal compensation for serving as an employee of Sanofi. Miguel Alonso Alonso has stock in Sanofi.
Nazem Atassi, MD	Dr. Atassi has received personal compensation for serving as an employee of Sanofi. Dr. Atassi has stock in Sanofi.
Richard A. Hughes, MD	Dr. Hughes has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi.

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