Riliprubart’s Ascendancy: Phase II Results Illuminate Path Forward for CIDP Treatment

• Sanofi is presently engaged in the exploration of Riliprubart (SAR445088), a monoclonal antibody designed to selectively target the serine protease C1s, in pursuit of its potential therapeutic application in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).
• Riliprubart unveils compelling efficacy in CIDP treatment, fostering improvement among Standard-of-Care (SOC)-Treated participants and igniting a resurgence in SOC-Refractory individuals, accompanied by notable enhancements in disability measures and a reduction in plasma neurofilament light chain.

In the labyrinth of CIDP, where demyelination and inflammation entwine to ensnare the afflicted, complement activation emerges as a malevolent orchestrator of pathology. Riliprubart, a paragon of innovation, emerges as a valiant knight, wielding its humanized IgG4-monoclonal antibody to vanquish activated C1s, the nefarious agent of destruction. Its subcutaneous administration, a portal to convenience, beckons forth a new dawn of therapeutic possibilities, particularly for those ensnared by the clutches of treatment-resistant CIDP.

At the American Academy of Neurology conference 2024, Sanofi presented analysis of Phase II open-label trial (NCT04658472) wherein riliprubart was assessed across three cohorts: SOC-Treated, SOC-Refractory, and SOC-Naïve, spanning a 24-week Part-A followed by an optional 52-week Part-B. The primary endpoint measures relapse prevention (SOC-Treated) or response (SOC-Refractory/Naïve), with secondary endpoints including Inflammatory Neuropathy Cause and Treatment (INCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), Medical Research Council Sum Score  (MRC-SS), and grip-strength, analyzed using Bayesian statistics. In the crucible of interim-analysis, conducted amidst the tempest of May 2023, revelations unfold like petals unfurling at dawn. Among the SOC-Treated, 88% find solace or soar to new heights upon embracing riliprubart, with 44% (N=11/25) ascending to realms of improvement, while 12% (N=3/25) succumb to the siren song of relapse. Behold, as 50% of SOC-Refractory souls (N=9/18) break free from the shackles of despair, their spirits lifted by riliprubart’s healing touch. Across the pantheon of disability and impairment measures, a symphony of improvement resounds, echoing through the halls of progress. A glimmer of hope flickers in the form of a trend-level reduction in plasma neurofilament light chain, a testament to riliprubart’s potential to quell the storm.

Yet, amidst the triumph, shadows lurk in the form of treatment-emergent adverse events (TEAEs), casting a pall over the battlefield. Sixty percent (N=15/25) of SOC-Treated souls and 72% (N=13/18) of SOC-Refractory brethren bear witness to the toll of this crusade. Alas, two valiant souls, burdened by the weight of significant comorbidities, journey beyond the veil. Amongst the cacophony of afflictions, headache, fatigue, and nasopharyngitis reign supreme.

Conclusion: As the dust settles and the curtain draws to a close, the saga of riliprubart unfolds as a testament to resilience and innovation. In its preliminary foray, riliprubart showcases a symphony of promise, heralding a new chapter in the annals of CIDP management. Yet, the journey has only just begun, and the path to enlightenment lies shrouded in the mists of Phase III trials, where riliprubart’s mettle shall be tested anew.