CIDP Agent Riliprubart Reduces Neurofilament Light in Phase 2 Subanalysis

Luis Querol Gutierrez, MD, PhD

Recently presented data from an open-label phase 2 study (NCT04658472) revealed that treatment with investigational riliprubart (Sanofi) led to notable reductions in plasma neurofilament light (NfL) levels among patients with chronic inflammatory demyelinating polyneuropathy (CIDP). More notably, greater reductions in NfL levels correlated with higher treatment response rates, as measured by Inflammatory Neuropathy Cause and Treatment (INCAT) Disability score.¹

The global, multicenter study evaluated riliprubart in three cohorts of patients with CIDP: those receiving standard-of-care (SOC) therapy with residual disability (SOC-treated), those who were refractory or inadequately responsive to SOC (SOC-refractory), and those who had never received SOC treatment (SOC-naïve). All participants received 24 weeks of treatment (Part A), with an optional 52-week extension phase (Part B).

The analysis comprised interim 24-week data from 48 SOC-treated and 18 SOC-refractory participants from the study. Presented at the 2025 Peripheral Nerve Society (PNS) Annual Meeting, held May 17-20, in Edinburgh, Scotland, investigators observed a 31% reduction in NfL geometric mean (GM) ratio (0.69 [±1.67]) among patients treated with riliprubart, a humanized IgG4-monoclonal antibody. Led by Luis Querol Gutierrez, MD, PhD, a neurologist at the Hospital de la Santa Creu, in Barcelona, Spain, the reduction in NfL GM ratio was similar regardless of whether patients were SOC-refractory (0.70 [±1.64]) or SOC-treated (0.69 [±1.68]).

Additional data from the analysis revealed a similar reduction in plasma NfL among atypical (0.50 [±1.85]) vs typical CIDP (0.77 [±1.54]) as well as high (0.66 [±1.88]) vs low baseline NfL levels (0.85 [±1.26]), and baseline INCAT scores (0.60 [±1.76] vs 0.75 [±1.6]). At week 24, the percentage of INCAT responders was higher among those who demonstrated greater reductions in NfL from baseline (SOC-refractory: 67% [4 of 5]; SOC-treated: 69% [11 of 16]) vs lower reductions (SOC-Refractory: 33% [2 of 6]; SOC-treated: 31% [5 of 16]).

Riliprubart, previously known as SAR445088, is a selective inhibitor of active C1s, a serine protease within the C1 complex that initiates the classical complement pathway. By blocking this pathway, the agent may disrupt key inflammatory processes driving demyelination and axonal injury in CIDP.

READ MORE: New Treatments, Global Collaboration Highlight 2025 Peripheral Nerve Society Annual Meeting

Previous 24-week and 52-week data from the phase 2 study were presented at the 2024 PNS Annual Meeting. Overall, treated participants demonstrated improvement in patient-reported fatigue and quality-of-life measures across all cohorts through the initial 24 weeks and an additional 24 weeks of treatment. These included the RASCH-built Fatigue Severity Scale and the EuroQoL Visual Analogue Scale, a health-related quality of life assessment.²

At 24 weeks, riliprubart led to improved or sustained disease activity in 87% of SOC-treated participants, with over half (52%) showing improvement beyond their prior therapy; 73% maintained this response after an additional year. Among SOC-naïve patients, 92% improved or remained stable at 24 weeks, with 71% sustaining their response through 48 weeks. In the SOC-refractory group, 89% showed improvement or stability at 24 weeks—50% with marked improvement—and 89% of those maintained their response after one year.

Riliprubart is currently being assessed in 2 phase 3 studies, dubbed MOBILIZE (NCT06290128) and VITALIZE (NCT06290141), that will continue to assess its effects as a potential treatment for CIDP. These trials, launched in 2024, are actively enrolling participants across 28 countries in North and South America, Europe, and Asia. Treatment duration in both trials is 48 weeks: 24-week double-blind period (Part A), followed by a 24-week open-label period (Part B).³

In part A, participants will be randomized 1:1 to receive riliprubart or placebo (MOBILIZE; n = up to 140) and riliprubart or intravenous immunoglobulin (IVIg; VITALIZE; n = up to 160). Patients may be eligible for these double-blind, placebo-controlled studies if they have CIDP diagnosed based on 2021 EAN/PNS-guidelines with INCAT scores 2-9. The primary end points are percentage of participants responding (Part A), considered at least a 1-point decrease in adjusted INCAT score, and long-term efficacy of riliprubart in adjusted INCAT-score (Part b).

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REFERENCES
1. Querol L, Hourcade S, Chow T, et al. Exploratory Biomarker Analyses in a Phase 2 Trial of Riliprubart for Chronic Inflammatory Demyelinating Polyneuropathy. Presented at: 2025 PNS Annual Meeting; May 17-20. Edinburgh, Scotland. ABSTRACT 281.
2. Media Update: Riliprubart one-year results from phase 2 study underpin the potential as a first-in-class treatment in chronic inflammatory demyelinating polyneuropathy. News release. June 25, 2024. Accessed May 16, 2025. https://www.sanofi.com/en/media-room/press-releases/2024/2024-06-25-20-30-00-2904145
3. Sommer C, Querol L, Allen J, et al. Riliprubart Phase 3 MOBILIZE and VITALIZE Trials for CIDP are Actively Enrolling Globally. Presented at 2025 PNS Annual Meeting; May 17-20. Edinburgh, Scotland. ABSTRACT 280