A More Selective Immune Approach to CIDP With Riliprubart: Claudia Sommer, MD

WATCH TIME: 3 minutes

"It’s a very logical mechanism—and now, seeing that it works in patients, that’s what truly matters in CIDP care."

Chronic inflammatory demyelinating polyneuropathy (CIDP), an autoimmune condition that affects the myelin sheath around peripheral nerves, has been typically treated through corticosteroids, plasma exchange, and intravenous immunoglobulin therapy (IVIg). The disorder, which cause muscle weakness and abnormal sensations, is treatable; however, patients may experience relapse, which requires additional follow-up and management. CIDP is closely related to Guillain-Barré syndrome (GBS), and many healthcare providers consider CIDP to be the long-term form of GBS.

The 2025 Peripheral Nerve Society (PNS) Annual Meeting, held May 17-20, in Edinburgh, Scotland, stands as the biggest global gathering focused on peripheral nerve biology and medicine. Several new therapeutics were introduced at the meeting, including data on Sanofi’s riliprubart, a monoclonal antibody that targets complement component C1s, a key enzyme in the classical complement pathway. In the latest phase 2 study (NCT04658472), treatment with the agent led to reductions in neurofilament light (NfL) levels, a biomarker of neuroaxonal damage, over a 24-week open-label period. More notably, these reductions correlated with higher treatment response rates, as measured by Inflammatory Neuropathy Cause and Treatment (INCAT) Disability score.

During the event, NeurologyLive^® sat down with Claudia Sommer, MD, president-elect of PNS, to discuss the mechanism and promise of riliprubart amid an evolving CIDP treatment landscape. Sommer, who serves as a professor of neurology at the University Hospital of Wurzburg, Germany, spoke on the scientific rationale behind the therapeutic, noting that the targeted actions prevents downstream immune responses such as T and B cell activation, among other promising effects. Above all, she discussed how riliprubart’s precision-based approach distinguishes itself from prior immune-targeted therapies and reflects a broader trend toward mechanism-specific strategies in the evolving CIDP treatment landscape.

Click here for more PNS 2025 coverage.

REFERENCE
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.

Transcript edited below for clarity.

Claudia Sommer, MD: When we think about the pathophysiology of CIDP, we often refer to this conceptual “cartoon” that illustrates the interplay of immune components. In it, you see T cells, B cells, autoantibodies, cytokines, macrophages, and complement factors—all contributing to nerve damage in different ways.

The conventional therapies we’ve used likely act on several of these components, though to varying degrees. What’s exciting now is that emerging treatments are aiming for greater specificity. For example, the novel FcRn inhibitors work by reducing overall immunoglobulin levels, thereby also reducing any pathogenic autoantibodies.

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. That’s a crucial point: even while we inhibit one pathway to prevent nerve damage, the patient’s ability to fight infections is preserved.

By blocking this early part of the cascade, riliprubart prevents downstream effects such as activation of T and B cells and the formation of the membrane attack complex. This complex is what ultimately causes damage to the myelin or axons, often at the nodes of Ranvier, sometimes by attracting macrophages that directly destroy those structures.

The mechanism always made sense—it was a logical therapeutic target from the beginning. But now, seeing that it actually works in patients, as shown in the early trial data, is what truly matters. We’ve seen other mechanisms before, often borrowed from the MS world, that didn’t translate well to CIDP. This time, we may have something that does.