FDA Approves Tremfya for Crohn's Disease

This milestone builds upon the FDA approval of Tremfya in moderately to severely active ulcerative colitis (UC), one of two main forms of inflammatory bowel disease (IBD), which impacts the lives of nearly three million Americans. Tremfya is the first and only approved fully-human, dual-acting monoclonal antibody that blocks IL-23 while also binding to CD64, a receptor on cells that produce IL-23. 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 CD.

“Despite the progress in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options,” said Remo Panaccione, MD, FRCPC, Professor of Medicine and the Director of the Inflammatory Bowel Disease Unit at the University of Calgary and lead investigator of the Phase III GRAVITI study. “The approval of Tremfya offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers that have not been available before.”

This approval is supported by results from multiple rigorous Phase III trials evaluating more than 1,300 patients with moderately to severely active CD who failed or were intolerant to conventional therapy (i.e. corticosteroids or immunomodulators) or biologics. The GRAVITI study evaluated Tremfya SC induction and maintenance therapy versus placebo. Data from the GALAXI clinical program showed Tremfya was superior to Stelara in all pooled endoscopic endpoints, the only IL-23 inhibitor to achieve this in a double-blinded registrational program. The comprehensive results from these Phase III studies demonstrated the robust efficacy of SC or IV Tremfya in achieving clinical and endoscopic endpoints.

“Tremfya is the first and only IL-23 inhibitor that offers a fully subcutaneous treatment option for moderately to severely active Crohn’s disease. With the approval of Tremfya, it is now possible to achieve meaningful improvements in clinical and endoscopic outcomes with the flexibility of self-administration from the start,” said Chris Gasink, MD, Vice President, Medical Affairs, Gastroenterology & Autoantibody, Johnson & Johnson Innovative Medicine. “Tremfya provides people living with Crohn’s disease and their healthcare providers a new treatment option that is supported by data from multiple Phase III studies, including pooled analyses showing statistical superiority versus Stelara across four endoscopic or combined clinical and endoscopic endpoints.”

This approval marks the fourth indication for Tremfya in the U.S., following moderate-to-severe plaque psoriasis in July 2017, active psoriatic arthritis in July 2020 and moderately to severely active UC in September 2024, underscoring Johnson & Johnson’s long-standing legacy in innovation and commitment to patients living with chronic immune-mediated diseases, including IBD. In November 2024, Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) to the FDA seeking approval of a SC induction regimen of Tremfya for the treatment of adults with moderately to severely active UC, based on results of the Phase III ASTRO study. 

ABOUT THE GRAVITI STUDY (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). Patients received guselkumab 400 mg SC q4w (x3) followed by guselkumab 200 mg SC q4w; or guselkumab 400 mg SC q4w (x3) followed by guselkumab 100 mg SC q8w; or placebo. The maintenance doses in GRAVITI (200 mg SC q4w and 100 mg SC q8w) are the same as those evaluated in the Phase III GALAXI 2 and GALAXI 3 studies that evaluated the efficacy and safety of IV induction followed by SC maintenance therapy in patients with moderate to severely active Crohn’s disease. Similar to GALAXI, GRAVITI employed a treat-through design, in which patients were randomized to guselkumab at Week 0 and remained 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 ➔ 100 mg SC q8w) if rescue criteria were met at Week 16.

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. Patients received guselkumab 200 mg intravenous induction at Weeks 0, 4 and 8 followed by guselkumab 200 mg subcutaneous maintenance every 4 weeks; or guselkumab 200 mg intravenous induction at Weeks 0, 4 and 8, followed by guselkumab 100 mg subcutaneous maintenance every 8 weeks; or a biologic active control; or placebo. Participants randomized to placebo were able to receive ustekinumab if clinical response was not met at Week 12. Of the 873 individuals pooled across the GALAXI 2 & 3 dataset, 456 (52 percent) had prior history of inadequate response to biologics, 365 (42 percent) were biologic-naïve and 52 (6 percent) were biologic experienced without documented inadequate response or intolerancei The GALAXI 2 and GALAXI 3 studies were the first-ever double-blind registrational head-to-head clinical trials to demonstrate superiority versus ustekinumab in Crohn’s disease, showing guselkumab was superior to ustekinumab in all endoscopic-based endpoints when analyzed with pooled data.