Abstract Details

Title 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)

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S15 - Autoimmune Neuromuscular Diseases: New Observations and Therapeutic Approaches (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

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.

Objective Report preliminary efficacy and safety results for riliprubart, a novel complement C1s-inhibitor, in people with CIDP.

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.

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 $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 $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. 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 $500-$4,999 for serving as a Consultant for Johnson & Johnson. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. 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.
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 $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunics. The institution of Dr. Van Doorn has received personal compensation in the range of $0-$499 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 $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Van Doorn has received publishing royalties from a publication relating to health care.
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.
Xiaodong Luo	No disclosure on file
Miguel Alonso Alonso	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. Dr. Hughes has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hansa Biopharma. Dr. Hughes has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic.