Sanofi's investigational complement C1s inhibitor, riliprubart, has demonstrated promising efficacy and safety in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), according to interim results from an ongoing Phase 2 study presented at the 2024 Peripheral Nerve Society Annual Meeting in Montreal.
The global, multicenter, open-label study evaluated riliprubart in three distinct patient cohorts: those currently receiving standard-of-care (SOC) treatment with residual disability (SOC-treated), those who experienced inadequate response or failure with SOC (SOC-refractory), and those who had not received SOC treatment in the previous six months (SOC-naïve).
Strong Efficacy Across All Patient Groups
The study consisted of two parts: a 24-week treatment period (Part A) followed by an optional one-year extension (Part B). Results from Part A showed that 87% of SOC-treated participants improved or remained stable after switching to riliprubart, with 52% experiencing greater improvement than with their previous therapy.
For patients who had previously failed standard treatments, the results were particularly encouraging. Among SOC-refractory participants, 89% improved or remained stable with riliprubart, with half showing clear improvement. Similarly, 92% of SOC-naïve participants improved or remained stable during the initial treatment period.
Dr. Luis Querol Gutierrez from the Department of Neurology at Hospital de la Santa Creu i Sant Pau in Barcelona emphasized the significance of these findings: "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 2 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."
Sustained Benefits and Biomarker Improvements
The extended treatment results from Part B reinforced riliprubart's potential, with 73% of SOC-treated participants, 89% of SOC-refractory participants, and 71% of SOC-naïve participants maintaining their response after approximately one year of treatment.
Beyond clinical measures, riliprubart demonstrated improvements in patient-reported outcomes, including reductions in fatigue and enhanced quality of life across all cohorts. The treatment also reduced neurofilament light chain (NfL) levels—a biomarker associated with nerve damage—by 35% across all groups throughout the study period, suggesting potential neuroprotective effects.
"CIDP is a debilitating disease, often with challenging comorbidities, and nearly a third of patients experience failure to or do not adequately respond to available therapies," said Dr. Erik Wallström, Global Head of Neurology Development at Sanofi. "Our riliprubart CIDP study is the only evaluating a broad spectrum of participants, including those who experienced failure of standard-of-care therapy, as well as the first study to investigate neurofilament light chain levels as a key biomarker of CIDP progression."
Safety Profile and Ongoing Development
Riliprubart demonstrated a manageable safety profile throughout the study. Treatment-emergent adverse events occurred in 64.6% of SOC-treated participants and 88.9% of SOC-refractory participants. The most common adverse events across all cohorts (≥12%) were headache, nasopharyngitis, and COVID-19. Two deaths were reported in participants with significant medical comorbidities beyond CIDP.
Based on these promising results, Sanofi has initiated two global Phase 3 studies: MOBILIZE (NCT06290128), evaluating riliprubart in adults with CIDP who experienced failure or inadequate response to SOC treatment, and VITALIZE (NCT06290141), studying the drug in adults with CIDP receiving maintenance treatment with intravenous immunoglobulin.
Addressing an Unmet Medical Need
CIDP is a rare neurological condition characterized by progressive weakness and sensory impairment in the extremities due to immune-mediated attacks on the myelin sheaths surrounding peripheral nerve cells. Despite available therapies, approximately 30% of people with CIDP do not respond to standard treatments, and among those who do respond, about 70% experience incomplete relief from symptoms.
Riliprubart represents a potential first-in-class treatment approach for CIDP. As an IgG4 humanized monoclonal antibody, it selectively inhibits activated C1s in the classical complement pathway of the innate immune system. By blocking C1s, riliprubart may inhibit key inflammatory mechanisms driving demyelination and axonal damage in CIDP.
The drug's development underscores the ongoing efforts to address the significant unmet needs in CIDP treatment, particularly for patients who fail to respond adequately to current standard therapies or experience residual disability despite treatment.
