Guselkumab (Tremfya) Wins Approval for Crohn Disease, Fourth Indication for Immune-Mediated Diseases

The US FDA on Thursday approved guselkumab (Tremfya; Johnson & Johnson) for the treatment of adults with moderately to severely active Crohn disease (CD). The approval follows the agency's September 2024 green light for the dual-acting monoclonal antibody targeting interleukin (IL)-23 to treat adults with ulcerative colitis of the same severity.

_{©MichaelVi/stock.adobe.com}

The approval is based on the FDA's review of data from multiple phase 3 clinical trials that included results of the GALAXI program. In this head-to-head study guselkumab proved superior to ustekinumab (Stelara; Janssen) across pooled endoscopic endpoints, making guselkumab the "only IL-23 inhibitor to achieve this in a double-blinded registrational program," according to the Johnson & Johnson March 20 announcement. With this approval, guselkumab also becomes the only IL-23 inhibitor with induction options for both subcutaneous (SC) and intravenous (IV) administration.

"Despite the progress in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options," Remo Panaccione, MD, FRCPC, professor of medicine and director of the Inflammatory Bowel Disease Unit at the University of Calgary and lead investigator of the phase 3 GRAVITI study, said in the news release. "The approval of [guselkumab] offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous [induction] regimen offers choice and flexibility for patients and providers that have not been available before."

Inflammatory bowel disease (IBD) affects approximately 1 in every 100 Americans, according to the Crohn's & Colitis Foundation.² Although the disease is known to have a heritable component, (as many as 1 in 4 with IBD have a first degree relative with one of the conditions), family history alone is not sufficient to predict who will manifest the disease.² Early detection and diagnosis leading to treatment can help avoid risk of colorectal cancer, according to experts.³

Guselkumab Phase 3 Development Program

The phase 3 development program evaluated more than 1,300 adults with moderately to severely active CD who had inadequate response or intolerance to conventional therapy or biologics, according to Johnson & Johnson. In the GRAVITI study, SC induction therapy with guselkumab demonstrated a clinical remission rate of 56% versus 22% with placebo (P <.001) and an endoscopic response rate of 34% compared to 15% (P <.001) at week 12. The GALAXI 2 and GALAXI 3 studies evaluated IV induction of guselkumab. Results of GALAXI 2 showed a clinical remission rate of 47% with the study drug vs 20% with placebo (P <.001) and an endoscopic response rate of 36% compared to 9% (P <.001). Findings were similar for GALAXI 3, which demonstrated clinical remission rate of 47% with guselkumab vs 20% with placebo (P <.001) and an endoscopic response rate of 34% compared to 13% with placebo (P <.001).

The March 20, 2025 approval makes guselkumab the first and only IL-23 inhibitor offering both subcutaneous (SC) and intravenous (IV) induction options, for the treatment of adults with moderately to severely active Crohn disease.

Guselkumab continued to show significant efficacy at week 48 in the GRAVITI study, the company reported, with SC maintenance therapy at 100 mg every 8 weeks resulting in a clinical remission rate of 59% compared to 17% with placebo. Endoscopic response was observed in 39% of patients versus 5% with placebo, while endoscopic remission rates were 31% versus 6%. In the group receiving the higher 200-mg maintenance dose regimen (200 mg every 4 weeks) 65% of participants reached clinical remissions compared to 17% in the placebo group, with endoscopic remission rates of 40% vs 6%, respectively.

"With the approval of [guselkumab], it is now possible to achieve meaningful improvements in clinical and endoscopic outcomes with the flexibility of self-administration from the start," Chris Gasink, MD, vice president, medical affairs, gastroenterology & autoantibody, Johnson & Johnson Innovative Medicine, said. "[Guselkumab] provides people living with Crohn’s disease and their healthcare providers a new treatment option that is supported by data from multiple Phase 3 studies, including pooled analyses showing statistical superiority versus [ustekinumab] across 4 endoscopic or combined clinical and endoscopic endpoints."

A long-term extension of the GALAXI studies will assess clinical, endoscopic, and safety outcomes of guselkumab treatment of Crohn disease over 5 years, according to Johnson & Johnson.

Guselkumab adds the new indication to approvals for plaque psoriasis (2017) and psoriatic arthritis (2020), and the most recent for ulcerative colitis (2024).

References
1. Tremfya (guselkumab) demonstrates superiority versus Stelara (ustekinumab) in phase 3 Crohn’s disease program. News release. Johnson & Johnson. March 21, 2025. Accessed March 21, 2025. https://www.jnj.com/media-center/press-releases/tremfya-guselkumab-demonstrates-superiority-versus-stelara-ustekinumab-in-phase-3-crohns-disease-program.
2. Overview of Crohn's disease. Crohn's & Colitis Foundation. Accessed March 21, 2025. https://www.crohnscolitisfoundation.org/patientsandcaregivers/what-is-crohns-disease/overview
3. Ginsberg S. 11 facts about Crohn's disease you might not know but should. Creaky Joints. October 18, 2018. Accessed March 21, 2025. https://creakyjoints.org/education/crohns-disease-facts/