Application submitted to FDA seeking approval of Tremfya (guselkumab) for the treatment of moderately to severely active Crohn’s disease

This marks the second submission to the FDA for Tremfya in inflammatory bowel disease this year following an application in March for moderately to severely active ulcerative colitis.

The latest submission includes results from the Phase III GALAXI program, which was featured as a late-breaking oral presentation at Digestive Disease Week (DDW) 2024 last month. The GALAXI 2 and GALAXI 3 studies were the first-ever double-blind registrational head-to-head trials to demonstrate superiority versus ustekinumab in Crohn’s disease. Tremfya successfully met the co-primary endpoints for both SC maintenance doses (200 mg every 4 weeks [q4w] and 100 mg every 8 weeks [q8w]) compared to placebo in each individual study and demonstrated superiority to ustekinumab in multiplicity-controlled endoscopic endpoints based on data pooled from both studies.

The submission also includes results from the Phase III GRAVITI investigational study of Tremfya SC induction therapy in adult patients with moderately to severely active Crohn’s disease, which met the co-primary endpoints, achieving statistically significant and clinically meaningful outcomes for clinical remission at Week 12 as well as endoscopic response at Week 12. In addition, all multiplicity-controlled endpoints were met compared to placebo at Week 12, Week 24 and Week 48. The results from GALAXI and GRAVITI show that Tremfya has the potential to become the only IL-23 inhibitor to offer both subcutaneous or intravenous induction options for the treatment of Crohn’s disease, and, if approved, will offer choice and versatility for patients and providers.

Tremfya is the first approved fully-human, dual-acting monoclonal antibody that blocks IL-23 while also binding to CD64, a receptor on cells that produce IL-23.5 IL-23 is a cytokine secreted by activated monocyte/macrophages and dendritic cells that is known to be a driver of immune-mediated diseases including Crohn’s disease. Tremfya, the first-in-class IL-23 inhibitor, received U.S. FDA approval in July 2017 for the treatment of adult patients with moderate-to-severe plaque psoriasis and was subsequently approved for adults with active psoriatic arthritis in July 2020.

Janssen-Cilag International NV, a Johnson & Johnson company, previously announced the submission of applications to the European Medicines Agency (EMA) seeking to expand the Marketing Authorization Application for Tremfya to include the treatment of adult patients with moderately to severely active ulcerative colitis and moderately to severely active Crohn’s disease.

ABOUT THE GALAXI PROGRAM (NCT03466411) ;GALAXI is a randomized, double-blind, placebo-controlled, active-controlled (ustekinumab), global, multicenter Phase II/III program designed to evaluate the efficacy and safety of guselkumab in participants with moderately to severely active Crohn’s disease with inadequate response/intolerance to conventional therapies (corticosteroids or immunomodulators) and/or biologics (TNF antagonists or vedolizumab). GALAXI includes a Phase II dose-ranging study (GALAXI 1) and two independent, identically designed confirmatory Phase III studies (GALAXI 2 and 3). Each GALAXI study employed a treat-through design in which participants remained on the treatment to which they were initially randomized and includes a long-term extension study that will assess clinical, endoscopic, and safety outcomes with guselkumab through a total of five years. Participants randomized to placebo were able to receive ustekinumab if clinical response was not met at Week 12.

ABOUT THE GRAVITI PROGRAM (NCT05197049): GRAVITI is a randomized, double-blind, placebo-controlled Phase III study to evaluate guselkumab SC induction therapy (400 mg at Weeks 0, 4, and 8) in patients with moderately to severely active Crohn’s disease who experienced an inadequate response or failed to tolerate conventional therapy (i.e., corticosteroids or immunomodulators) or biologic therapy (TNF antagonists or vedolizumab). The maintenance doses in GRAVITI are the same as those evaluated in GALAXI (200 mg SC q4w and 100 mg SC q8w).3The study employed a treat-through design, in which patients are randomized to guselkumab at Week 0 and remain on that regimen throughout the study, regardless of clinical response status at the end of induction. Participants randomized to placebo were able to receive guselkumab (400 mg SC q4w x3 arrow 100 mg SC q8w) if rescue criteria were met at Week 16.