FDA Approves Guselkumab (Tremfya) For Crohn Disease

The US Food and Drug Administration (FDA) has approved guselkumab (Tremfya) for the treatment of adults with moderately to severely active Crohn disease.

According to a March 20, 2025 announcement from Johnson and Johnson, the approval is based on data from multiple phase 3 trials, including the GALAXI trials, which found guselkumab outperformed ustekinumab (Stelara) for multiple endoscopic endpoints. The agent now boasts indications for moderately to severely active Crohn disease and moderately to severely active ulcerative colitis (UC).

"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 3 GRAVITI study. "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 regimen offers choice and flexibility for patients and providers that have not been available before."

In their release, Johnson and Johnson highlighted the dosing information for treatment of moderately to severely active Crohn disease as follows:

• The recommended subcutaneous induction dosage is 400 mg (given as 2 consecutive injections of 200 mg each, dispensed in 1 Induction Pack) at weeks 0, 4, and 8. Guselkumab is also available in a 200 mg prefilled syringe. For the IV induction option, 200 mg IV infusions are administered at weeks 0,4, and 8.1
• Recommended maintenance dosage is 100 mg administered by subcutaneous injection at week 16, and every 8 weeks thereafter, or 200 mg administered by subcutaneous injection at week 12, and every 4 weeks thereafter. Healthcare providers are instructed to use the lowest effective recommended dosage to maintain therapeutic response.1

The approval marks the fourth indication for guselkumab in the US. The agent, which holds the distinction of being the first IL-23 inhibitor offering both subcutaneous and intravenous induction options, received initial approval from the FDA in 2017 for treatment of moderate-to-severe plaque psoriasis. This approval was followed by subsequent indications for active psoriatic arthritis and moderately to severely active UC in 2020 and 2024, respectively.1

At the time of the March 2025 approval announcement, guselkumab was under review for an additional indication of a subcutaneous induction regimen of guselkumab for the treatment of adults with moderately to severely active UC, based on results of the Phase 3 ASTRO study.1,2

The clinical trial program used to support the Crohn disease approval included the GRAVITI, GALAXI 2, and GALAXI 3 studies. In total, the evidence base included more than 1300 patients with moderately to severely active CD who failed or were intolerant to conventional therapy or biologics.1

The GRAVITI study assessed the impact of guselkumab 400 mg administered subcutaneously at weeks 0, 4, and 8, with results demonstrating a clinical remission rate of 56% compared to 22% with placebo (P < .001) and an endoscopic response rate of 34% compared to 15% (P < .001) at week 12. In the GALAXI 2 study, patients receiving guselkumab 200 milligrams administered intravenously at the same intervals achieved a clinical remission rate of 47% compared to 20% with placebo (P < .001) and an endoscopic response rate of 36% compared to 9% with placebo (P < .001). Similarly, the GALAXI 3 study reported a clinical remission rate of 47% with guselkumab 200 mg administered intravenously relative to 20% with placebo (P < .001) and an endoscopic response rate of 34% relative to 13% with placebo (P < .001).1

By week 48 in the GRAVITI study, patients receiving guselkumab 100 mg administered subcutaneously every 8 weeks starting at week 16 achieved a clinical remission rate of 59% compared to just 17% with placebo, an endoscopic response rate of 39% compared to 5%, and an endoscopic remission rate of 31% compared to 6%. Additionally, deep remission, defined as both clinical and endoscopic remission, was observed in 26% of patients compared to 4% with placebo.1

In the group receiving guselkumab 200 mg administered subcutaneously every 4 weeks starting at week 12, clinical remission was achieved in 65% of patients compared to 17% with placebo, with an endoscopic response rate of 48% compared to 5% and an endoscopic remission rate of 40% versus 6%. Deep remission was reported in 34% of patients receiving guselkumab 200 mg administered subcutaneously every 4 weeks compared to 4% with placebo.1

"[Guselkumab] 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 [guselkumab], 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 of Medical Affairs in Gastroenterology & Autoantibody at Johnson & Johnson Innovative Medicine.1 "[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 STELARA across 4 endoscopic or combined clinical and endoscopic endpoints."

References:

1. Johnson and Johnson. U.S. FDA approves TREMFYA® (guselkumab), the first and only IL-23 inhibitor offering both subcutaneous and intravenous induction options, for adult patients with moderately to severely active Crohn’s disease. JNJ.com. March 20, 2025. Accessed March 20, 2025. https://www.investor.jnj.com/news/news-details/2025/U-S--FDA-approves-TREMFYA-guselkumab-the-first-and-only-IL-23-inhibitor-offering-both-subcutaneous-and-intravenous-induction-options-for-adult-patients-with-moderately-to-severely-active-Crohns-disease/default.aspx.

2. Johnson and Johnson. Johnson & Johnson seeks U.S. FDA approval for subcutaneous induction regimen of TREMFYA® (guselkumab) in ulcerative colitis, a first for an IL-23 inhibitor. JNJ.com. November 22, 2024. Accessed March 20, 2025. https://www.jnj.com/media-center/press-releases/johnson-johnson-seeks-u-s-fda-approval-for-subcutaneous-induction-regimen-of-tremfya-guselkumab-in-ulcerative-colitis-a-first-for-an-il-23-inhibitor.