Abstract Details

Title Phase 2 Efficacy and Safety of Riliprubart, a C1s-Complement Inhibitor, in Chronic Inflammatory Demyelinating Polyneuropathy

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S16 - Updates on Nerve and Muscle Disorders (2:36 PM-2:48 PM)

Poster/Presentation
Number 009

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.

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.
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.
Xiaodong Luo (Sanofi)	Xiaodong Luo has received personal compensation for serving as an employee of Sanofi. An immediate family member of Xiaodong Luo has received personal compensation for serving as an employee of Beigene. Xiaodong Luo has stock in Sanofi. An immediate family member of Xiaodong Luo has stock in Beigene. An immediate family member of Xiaodong Luo has stock in Johnson and Johnson.
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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