Janssen reveals positive top-line results from two phase 3 trials of Tremfya (guselkumab) in patients with moderate to severe arthritis (PsA). Guselkumab is a human monoclonal antibody that blocks the p19 subunit of interleukin (IL)-23. The DISCOVER-1 (N=381) and DISCOVER-2 (N=739) trials compared subcutaneous guselkumab to placebo and lasted 52 weeks and 100 weeks respectively.
Janssen (subsidiary of Johnson and Johnson) reported that both studies met their primary endpoint of American College of Rheumatology 20% improvement (ACR20). Secondary endpoints included ACR50/70, resolution of soft tissue inflammation (enthesitis and dactylitis), disease activity (DAS-28 CRP), improvement in physical function (HAQ-D1), skin clearance (IGA) and quality of life (SF-36 PCS and MCS). Janssen will produce a New Drug Application which will include the full results from these clinical trials.
Guselkumab is an orally available, human, immunoglobulin G1 (IgG1) kappa, a monoclonal antibody directed against the p19 protein subunit of interleukin-23 (IL-23), with immunomodulating activity. Upon administration, guselkumab binds to the p19 subunit of IL-23, thereby blocking the binding of IL-23 to the IL-23 receptor. This inhibits IL-23-mediated signaling and the differentiation of CD4-positive T-cells into Th1 and Th17 cells. This prevents Th1- and Th17-mediated immune responses and inhibits the production of pro-inflammatory cytokines. This may prevent or reduce symptoms and severity of immune-mediated inflammatory disorders. IL-23 plays a key role in the regulation of inflammation and the immune system and modulates the release of various pro-inflammatory cytokines and chemokines. It is upregulated in various immune-mediated inflammatory disorders. Check for active clinical trials active clinical trials using this agent.