Model-Informed Drug Development-Based Bridging from Subcutaneous to Intravenous Secukinumab Dosing: Approval in...

The objective of this modeling and simulation analysis was to determine an intravenous (IV) secukinumab dosing regimen with steady-state exposure within the ranges of the approved subcutaneous (SC) regimens (300 and 150 mg every 4 weeks [q4w]) and to predict the efficacy and safety of this IV regimen for patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA). This approach was suggested by the US Food and Drug Administration (FDA) following review of the primary endpoint analysis results of secukinumab 3 mg/kg q4w IV in patients with PsA (INVIGORATE-2 study). Noting the higher exposure of the investigated IV regimen compared to the approved SC regimens, the FDA considered that the INVIGORATE-2 data available through Week 16 only may not convey sufficient safety information to support the benefit-risk assessment of this IV regimen. A population pharmacokinetic (popPK) analysis was conducted on a pool of 15 PsA or axSpA clinical trials to identify 1.75 mg/kg IV secukinumab q4w (with or without a 6 mg/kg IV loading dose at Week 0) as a regimen with steady-state exposure within the ranges of the approved SC regimens. This entitled its efficacy and safety to be assessed by full extrapolation from those of the approved SC regimens. This extrapolation was substantiated by the use of exposure-response analyses to predict the efficacy and safety of the IV regimen. Based on those analyses, this IV secukinumab regimen, not tested in clinical trials, was approved by the FDA for the treatment of patients with PsA and axSpA.