Confirmation of Fixed Quarterly Riliprubart Regimen in Patients with Cold Agglutinin Disease Using Population PK/PD and Exposure-Response Analyses.

Riliprubart is a second-generation, humanized immunoglobulin G4 that inhibits only the activated form of the C1s component of the proximal classical complement pathway. The clinical studies of riliprubart conducted thus far for the treatment of cold agglutinin disease (CAD), a rare autoimmune disease, include a Phase 1 first-in-human study in healthy participants and a Phase 1b single-dose study in 12 adult CAD patients. The objective of this study was to derive a riliprubart dosing regimen for CAD patients using model-informed drug development (MIDD) approaches utilizing available clinical data. A virtual population consisting of 1,000 CAD patients was created by sampling with replacement of the body weight distribution of CAD patients from a clinical database. The 3.5 g IV quarterly (q12w) riliprubart regimen with an additional 3.5 g IV dose on Day 29 is predicted to have a greater than threefold safety margin and >90% efficacy. The observed riliprubart concentration-time profiles from 9 CAD patients were consistently within the popPK simulated 90% prediction interval. Based on the totality of the efficacy, safety, and PK/PD data observed under clinical evaluation, the proposed dose regimen demonstrated suitability for CAD patients.