Model-Informed Drug Development-Based Approval of Intravenous Secukinumab for the Treatment of Adult Patients with Active Psoriatic Arthritis, Active Ankylosing Spondylitis, and Active Non-Radiographic Axial Spondyloarthritis.

Abstract

On October 6, 2023, the US Food and Drug Administration (FDA) approved an intravenous (IV) formulation and dosage of Cosentyx® (secukinumab), for the treatment of adult patients with active psoriatic arthritis (PsA), active ankylosing spondylitis (AS), and active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation. Clinical pharmacokinetics (PK), efficacy, and short-term placebo-controlled safety data were available from clinical studies (NCT04156620 and NCT04209205) with the to-be-marketed IV formulation using a maintenance dosage 3 mg/kg every 4 weeks (q4w), which was different from the dose approved (1.75 mg/kg q4w). The IV dosage of 3 mg/kg utilized in these two trials resulted in exposures (Cmax,ss) significantly higher than those for the approved subcutaneous (SC) regimens. Further, there is limited long-term safety information available for this 3 mg/kg q4w IV dose. To address this important limitation, a model-informed drug development (MIDD) approach was employed to leverage available clinical PK, efficacy, and safety data from the secukinumab development program to identify a maintenance IV dosing regimen, 1.75 mg/kg IV q4w, that better approximated the relevant SC secukinumab exposures for which efficacy and safety have been established. The MIDD analyses were used to support approval of this IV dosing regimen not directly studied in the indications sought for licensure, PsA, AS, and nr-AxSpA.