Guselkumab Receives FDA Approval for Adults With Moderately to Severely Active Crohn Disease

The FDA has approved guselkumab (Tremfya; Johnson & Johnson), the first and only IL-23 inhibitor that offers both subcutaneous (SC) and intravenous (IV) induction options, for the treatment of adults with moderately to severely active Crohn disease (CD), according to a news release from Johnson & Johnson.¹

Crohn disease is one of the main causes of inflammatory bowel disease. | Image Credit: © Berit Kessler - stock.adobe.com

The new indication for guselkumab follows the FDA’s approval of the IL-23 inhibitor in moderate to severe ulcerative colitis, at the time becoming the first and only approved fully human and dual-acting monoclonal antibody and offering a new option for one of the main forms of inflammatory bowel disease (IBD). Now, the FDA has expanded the treatment capability of guselkumab to include CD, another main form of IBD that impacts nearly 3 million patients in the US.^1,2

By blocking IL-23 while at the same time binding to CD64, guselkumab prevents the secretion of IL-23 by activated monocytes, macrophages, and dendritic cells that are known to drive immune-mediated diseases such as CD. Multiple phase 3 trials evaluated guselkumab, demonstrating its effectiveness across over 1000 patients with moderately to severely active CD who failed or were intolerant to conventional therapy—such as immunomodulators and corticosteroids—or biologics.^1,3

“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, lead investigator of the phase 3 GRAVITI study (NCT05197049), 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.”¹

In GRAVITI, in which investigators aimed to compare the effects of subcutaneous induction and maintenance therapy with guselkumab in adults with CD, over half of treated patients with 400 mg of guselkumab administered subcutaneously at weeks 0, 4, and 8 achieved clinical remission compared with placebo-treated patients. In 41.3% of those that received guselkumab SC induction therapy, an endoscopic response was observed, compared with 21.4% in the placebo group. Finally, week 48 follow-up data indicated a sustained and robust rate of clinical remission in patients treated with guselkumab compared with placebo.³

Investigators also analyzed guselkumab in comparison with ustekinumab (Stelara; Janssen Pharmaceuticals) in the GALAXI phase 3 clinical program. According to all pooled endoscopic end points, guselkumab was superior to ustekinumab, becoming the only IL-23 inhibitor to achieve this success in a double-blinded registrational program, according to Johnson & Johnson. Furthermore, in GALAXI 2 and GALAXI 3, guselkumab IV induction compared with placebo at weeks 0, 4, and 8 induced higher rates of clinical remission (47% vs 20%, P < .001; 47% vs 15%, P < .001 in GALAXI 2 and 3 respectively) and endoscopic response (36% vs 9%, P < .001; 34% vs 13%, P < .001 in GALAXI 2 and 3 respectively), indicating the broad effectiveness across both SC and IV formulations.¹

“[Guselkumab] is the first and only IL-23 inhibitor that offers a fully subcutaneous treatment option for moderately to severely active Crohn disease,” Chris Gasink, MD, vice president, medical affairs, gastroenterology and autoantibody, Johnson & Johnson Innovative Medicine, said in the news release. “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.”¹

REFERENCES

1. Johnson & Johnson. US 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. News Release. Released March 20, 2025. Accessed March 21, 2025. https://www.jnj.com/media-center/press-releases/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

2. Gallagher A. FDA approves guselkumab for treatment of ulcerative colitis. Pharmacy Times. Published September 12, 2024. Accessed March 21, 2025. https://www.pharmacytimes.com/view/fda-approves-guselkumab-for-treatment-of-ulcerative-colitis

3. Halpern L. New guselkumab data indicate robust effectiveness in Crohn disease, plaque psoriasis. Pharmacy Times. Published November 4, 2024. Accessed March 21, 2025. https://www.pharmacytimes.com/view/new-guselkumab-data-indicates-robust-effectiveness-in-crohn-disease-plaque-psoriasis