• Riliprubart demonstrated meaningful clinical benefit across all enrolled cohorts—SoC-Treated, SoC-refractory, and SoC-naïve—with improvement in functional measures (INCAT, I-RODS, MRC-SS, grip strength).
• Encouraged by consistent Phase II results, two global Phase III trials in CIDP have now been launched, positioning riliprubart as a potential new class of targeted complement inhibitors in immune-mediated neuropathies.

At EAN 2025, new results from the ongoing Phase II trial (NCT04658472) of riliprubart, a first-in-class, subcutaneously self-administered IgG4 monoclonal antibody targeting activated-C1s in the classical complement pathway, underscored its potential as a promising disease-modifying treatment for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). The trial included patients across three cohorts—standard-of-care (SoC)-Treated, SoC-Refractory, and SoC-Naïve—evaluating riliprubart over an initial 24-week treatment period (Part A), followed by a 52-week extension (Part B) assessing long-term efficacy and safety through Week 76.

Subgroup Analysis Highlights Consistent Benefits across Diverse Patient Populations

Preliminary subgroup analyses from Part A revealed that riliprubart delivered consistent clinical improvements regardless of baseline demographic or disease characteristics. Data from 48 SoC-treated and 18 SoC-Refractory participants demonstrated comparable Inflammatory Neuropathy Cause and Treatment (INCAT) response rates across key subgroups defined by age, sex, CIDP subtype, treatment history, and baseline Neurofilament-light (NfL) chain levels. Similar trends were observed across other functional measures, including grip strength, I-RODS, and MRC-SS, supporting riliprubart’s potential to provide benefit even in patients with residual disability or those unresponsive to prior immunoglobulin-based therapy.

76-week Data Support Durable Responses and Favorable Safety

As of the August 2024 cutoff, riliprubart showed encouraging long-term durability of effect. In the SoC-Treated group, 81.3% (39/48) entered Part B, with nearly half (47.9%) completing the full 76-week period. Relapse-free status at Week 76—defined as no ≥2-point worsening in adjusted INCAT score—suggested sustained disease control. Notably, 61.1% of SoC-refractory and 16.7% of SoC-naïve participants also completed Part B, with emerging data pointing to sustained responses and a manageable safety profile across cohorts.

Results from Parts A and B Showed

• For SOC-treated participants, 87% (42/48) improved or remained stable after switching from their previous SOC treatment to riliprubart after 24 weeks, including 52% (25/48) who experienced improvement above and beyond their previous therapy. 72% (29/40) sustained their response after an additional year of riliprubart treatment.
• For SOC-refractory participants, 89% (16/18) improved or remained stable with riliprubart after 24 weeks, with 50% (9/18) of this challenging cohort showing improvement. 89% (8/9) sustained their response after an additional year of riliprubart treatment.
• For SOC-naïve participants, 92% (11/12) improved or remained stable with riliprubart after 24 weeks, and 71% (5/7) sustained their response after an additional year of riliprubart treatment.
• Riliprubart improved participant-reported fatigue and quality-of-life outcomes across all cohorts throughout the initial 24 weeks and an additional year of treatment. The outcomes included reductions in the RASCH-built Fatigue Severity Scale and improvements in the EuroQoL Visual Analogue Scale, a health-related quality of life assessment.
• Riliprubart also reduced NfL levels across all three cohorts throughout the initial 24 weeks and an additional year of treatment, indicating that riliprubart may reduce disease activity and the underlying damage to nerve cells.

Looking Ahead: Toward Phase III Development

With riliprubart demonstrating both early and durable efficacy in CIDP, including in SoC-refractory populations, these results lay a solid foundation for Phase III advancement. The consistent response across a wide spectrum of patients strengthens riliprubart’s potential to address unmet needs in CIDP management, particularly for those with inadequate response or residual disability under current therapies.

Full efficacy and safety results through Week 76 are expected further to clarify riliprubart’s positioning in the CIDP treatment landscape and will be detailed during the meeting. 

KOL View

Many people living with CIDP do not fully respond to available therapies or do not respond at all, demonstrating a significant unmet need for this community. These Phase II data for riliprubart are encouraging, as they suggest that riliprubart’s unique mechanism of action reduces the overactive, damaging complement pathways that may drive disease progression. – Expert Opinion

Complement inhibitors, like riliprubart, are another promising class. These agents block the complement system at different stages of its activation. Riliprubart, in particular, inhibits the classical complement cascade early in its process. This is significant because it leaves the other arms of the complement system intact—those that are essential for defending against pathogens. – Expert Opinion

Conclusion

The 76-week results from this Phase II trial underscore riliprubart’s potential as a durable, mechanism-driven therapy in CIDP, offering meaningful benefit across treatment-refractory, naïve, and previously treated populations. Its ability to deliver consistent functional improvements, reduce biological markers of disease activity, and improve quality of life positions riliprubart as a strong candidate for Phase III development. These data mark a significant step forward in CIDP care, signaling a shift toward targeted complement inhibition as a viable strategy in the long-term management of this chronic autoimmune neuropathy.