Scaling Approaches for Pediatric Dose Selection: The Fremanezumab (AJOVY®) Journey to Select a Phase 3 Dose Using Pharmacokinetic Data from a Phase 1 Study.

Fremanezumab, a fully humanized IgG2Δa/kappa monoclonal antibody, selectively targets the calcitonin-gene-related peptide (CGRP) and prevents it from binding to the CGRP receptor. The safety, tolerability, pharmacokinetics (PK), and efficacy of fremanezumab for treating migraines administered as a once monthly 225 mg dose or a once quarterly 675 mg dose have been well characterized in adults. The fremanezumab exposure and body weight relationship supported the use of the approved 225 mg monthly adult dose for pediatric patients weighing ≥45 kg. In the pediatric Phase 3 program, a 120 mg dose for patients weighing <45 kg was determined using the results of an open-label study and a population PK modeling and simulation strategy. A thorough evaluation was conducted to further characterize the population PK of fremanezumab and assess the predictive performance of the adult population PK model when applied to the Phase 1 pediatric data, the predictive performance of alternative pediatric population PK models, and the predictive performance of the selected pediatric population PK model via a noncompartmental-based approach. This latter comparison to noncompartmental results provided additional evidence that the pediatric population PK model predicts the observed data well and supports the 120 mg monthly dose in patients weighing <45 kg.