Data from an open-label Phase 2 study has revealed that treatment with riliprubart, an investigational therapy developed by Sanofi, led to significant reductions in plasma neurofilament light (NfL) levels among patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The findings, presented at the 2025 Peripheral Nerve Society Annual Meeting in Edinburgh, Scotland, showed that greater reductions in NfL levels were associated with improved clinical outcomes.
The global, multicenter study (NCT04658472) evaluated riliprubart across three patient cohorts: those receiving standard-of-care (SOC) therapy with residual disability, those refractory to SOC, and treatment-naïve patients. The interim analysis focused on 24-week data from 48 SOC-treated and 18 SOC-refractory participants.
Significant Neurofilament Light Reduction
Researchers observed a 31% reduction in NfL geometric mean ratio (0.69 [±1.67]) among patients treated with riliprubart, a humanized IgG4-monoclonal antibody. The reduction was similar regardless of whether patients were SOC-refractory (0.70 [±1.64]) or SOC-treated (0.69 [±1.68]).
Dr. Luis Querol Gutierrez, a neurologist at the Hospital de la Santa Creu in Barcelona, Spain, who led the study, noted that similar reductions in plasma NfL were observed across various patient subgroups, including:
- Atypical (0.50 [±1.85]) vs typical CIDP (0.77 [±1.54])
- High (0.66 [±1.88]) vs low baseline NfL levels (0.85 [±1.26])
- Different baseline INCAT scores (0.60 [±1.76] vs 0.75 [±1.6])
Correlation with Clinical Response
The analysis revealed a notable correlation between NfL reduction and clinical improvement. At week 24, the percentage of responders based on Inflammatory Neuropathy Cause and Treatment (INCAT) Disability score was higher among those who demonstrated greater reductions in NfL from baseline:
- SOC-refractory patients: 67% (4 of 6) with greater NfL reduction vs 33% (2 of 6) with lower reduction
- SOC-treated patients: 69% (11 of 16) with greater NfL reduction vs 31% (5 of 16) with lower reduction
Mechanism of Action and Previous Findings
Riliprubart, previously known as SAR445088, works by selectively inhibiting 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.
Previous data from the same Phase 2 study presented at the 2024 PNS Annual Meeting showed that riliprubart led to improved or sustained disease activity in 87% of SOC-treated participants through 24 weeks, with over half (52%) showing improvement beyond their prior therapy. Among SOC-naïve patients, 92% improved or remained stable at 24 weeks.
The treatment also demonstrated positive effects on patient-reported outcomes, including improvements in fatigue and quality-of-life measures across all cohorts, as measured by the RASCH-built Fatigue Severity Scale and the EuroQoL Visual Analogue Scale.
Advancing to Phase 3 Trials
Based on these promising results, riliprubart is now being evaluated in two Phase 3 studies: MOBILIZE (NCT06290128) and VITALIZE (NCT06290141). These global trials, launched in 2024, are actively enrolling participants across 28 countries in North and South America, Europe, and Asia.
Both trials will follow patients for 48 weeks, consisting of a 24-week double-blind period followed by a 24-week open-label period. In MOBILIZE, participants will be randomized to receive either riliprubart or placebo, while VITALIZE will compare riliprubart to intravenous immunoglobulin (IVIg).
Patients may be eligible for these studies if they have CIDP diagnosed based on 2021 EAN/PNS-guidelines with INCAT scores of 2-9. The primary endpoints include the percentage of participants responding (considered at least a 1-point decrease in adjusted INCAT score) and long-term efficacy of riliprubart in adjusted INCAT score.
Long-term Safety and Efficacy
A separate long-term study is also underway to assess the safety and tolerability of riliprubart in individuals with CIDP over an extended period. This study, expected to continue until 2029, will monitor participants receiving subcutaneous injections of riliprubart, tracking the percentage who remain relapse-free and those showing improvement in their condition.
The study will measure changes in disability scores, grip strength, and muscle strength to comprehensively evaluate the treatment's effectiveness over time. This extended observation period will provide valuable data on the long-term management of CIDP with riliprubart.
For patients with CIDP, a rare autoimmune disorder characterized by progressive weakness and sensory loss due to damage to the peripheral nerves, these developments represent a potential new therapeutic option that could address the limitations of current standard treatments.
