Use of dose-exposure-response relationships in Phase 2 and Phase 3 guselkumab studies to optimize dose selection in...

Guselkumab is an anti-interleukin-23 monoclonal antibody for the treatment of moderate-to-severe psoriasis.

To evaluate the association between dose-response and exposure-response of guselkumab in Phase 2 and Phase 3 studies to optimize dose selection.

Serum guselkumab concentrations in Phase 2 and Phase 3 studies (VOYAGE 1 and VOYAGE 2) were measured using a validated immunoassay. Efficacy assessments included Physician's Global Assessment (PGA), Investigator's Global Assessment (IGA) and Psoriasis Area and Severity Index (PASI).

In Phase 2, a positive dose-response relationship was observed for PASI and PGA (5-mg through 100-mg dose regimens). Exposure-response analysis showed that patients with steady-state trough serum guselkumab concentrations ≥0.67 μg/mL achieved the highest levels of efficacy (PGA 0/1: 90.0%; PGA 0: 70.0%). The guselkumab 100-mg every 8-week (q8w) dose regimen, safe and well-tolerated in Phase 2, provided the highest serum guselkumab concentrations among all regimens studied and was selected for Phase 3. In Phase 3, 72.5% of patients achieved guselkumab concentrations ≥0.67 μg/mL at week 28, the level associated with the highest clinical responses in Phase 2, with patients achieving response rates of IGA 0/1: 91.2%, IGA 0: 55.3%, PASI 90: 83.8% and PASI 100: 49.1% at week 28.

The 100-mg guselkumab q8w dose regimen, based on the dose-exposure-response relationship from the Phase 2 study, produced the target serum concentration associated with high-level efficacy in the majority of patients in Phase 3. Phase 3 data further confirmed that guselkumab 100mg q8w is the optimum dosing regimen for treating patients with moderate-to-severe psoriasis.