Guselkumab

MONDAY, March 24, 2025 -- The U.S. Food and Drug Administration has approved Tremfya (guselkumab) for adult patients with moderately to severely active Crohn disease. This approval is the fourth indication for this dual-acting interleukin-23 inhibitor in the United States, making Tremfya the first and only interleukin-23 inhibitor offering both subcutaneous and intravenous induction options for adults with Crohn disease. The approval is based on data from three phase 3 trials. In the GRAVITI study, Tremfya (400 mg subcutaneous induction at weeks 0, 4, and 8) led to significantly higher clinical remission (56 versus 22 percent) and endoscopic response (34 versus 15 percent) when compared with placebo. Similar results were seen in the GALAXI 2 and GALAXI 3 trials, which compared Tremfya 200 mg intravenous induction at weeks 0, 4, and 8 with placebo. "Despite the progress in the management of Crohn's disease, many patients experience debilitating symptoms and are in need of new treatment options," lead investigator of the GRAVITI study, Remo Panaccione, M.D., from the University of Calgary in Alberta, Canada, said in a statement. "Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers that have not been available before." Approval of Tremfya was granted to Johnson & Johnson. More Information Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

TREMFYA ® is the only IL-23i to demonstrate clinical remission and endoscopic response, both at one year, with a fully subcutaneous induction regimen Supported by data from the GALAXI study, TREMFYA ® is the only IL-23i to show superiority versus STELARA ® in all pooled endoscopic endpoints within a double-blinded registrational trial TREMFYA ® approval in Crohn’s disease builds upon recent ulcerative colitis FDA approval, marking the fourth indication for this dual-acting IL-23i in the U.S. HORSHAM, PA, USA I March 20, 2025 I Johnson & Johnson (NYSE: JNJ ) today announced that the U.S. Food and Drug Administration (FDA) has approved TREMFYA ® (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’s disease (CD), a chronic inflammatory condition of the gastrointestinal tract. 1 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), 2 which impacts the lives of nearly three million Americans. 3 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. 4,5,6,7,8 “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 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 3 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. 6 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 3 studies demonstrated the robust efficacy of SC or IV TREMFYA ® in achieving clinical and endoscopic endpoints. Highlights from these pivotal studies showed: 6 “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 3 studies, including pooled analyses showing statistical superiority versus STELARA across four endoscopic or combined clinical and endoscopic endpoints.” TREMFYA ® dosing in the treatment of moderately to severely active CD: 6 Johnson & Johnson is committed to supporting access to all its treatments, including offering a patient support program called TREMFYA ® withMe. For commercially insured patients, adults who are prescribed TREMFYA ® for CD may be eligible to receive their first induction treatment in as little as 24 hours through TREMFYA ® withMe. 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, 6 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 3 ASTRO study. Editor’s Notes: a)  CD64+ cells are the predominant source of IL-23 in CD. Cells not expressing CD64 may also contribute to IL-23 production but to a lesser extent. 1,3 b)  “Only” based on approved selective IL-23 inhibitors for moderately to severely active CD as of March 2025. 6,7,8 c)   Based on in vitro studies in an inflammatory monocyte model. 4 d)   Moderately to severely active CD was defined as a Crohn’s Disease Activity Index (CDAI) score of ≥220 and a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of ≥6 (or ≥4 for subjects with isolated ileal disease). 6 e)  Clinical remission was defined as a CDAI score of <150. ,6 f)   Endoscopic response is defined as >50% improvement from baseline in SES-CD score. 6 g)  Endoscopic remission was defined as an SES-CD score ≤4 and at least a 2-point reduction from baseline and no subscore greater than 1 in any individual component. 6 h)  q4w is defined as every four weeks. 6 i)   q8w is defined as every eight weeks. 6 j)   Dr. Panaccione is a paid consultant for Johnson & Johnson. He has not been compensated for any media work. ABOUT THE GRAVITI STUDY ( NCT05197049 ) GRAVITI is a randomized, double-blind, placebo-controlled Phase 3 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). 10 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 3 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. 10 ABOUT THE GALAXI PROGRAM ( NCT03466411 ) GALAXI is a randomized, double-blind, placebo-controlled, active-controlled (ustekinumab), global, multicenter Phase 2/3 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). 11 GALAXI includes a Phase 2 dose-ranging study (GALAXI 1) and two independent, identically designed confirmatory Phase 3 studies (GALAXI 2 and 3). 11 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 intolerance. 12 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. ABOUT CROHN’S DISEASE Crohn’s disease is one of the two main forms of inflammatory bowel disease, which affects an estimated three million Americans. 3 Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract with no known cause, but the disease is associated with abnormalities of the immune system that could be triggered by a genetic predisposition, diet, or other environmental factors. 1 Symptoms of Crohn’s disease can vary, but often include abdominal pain and tenderness, frequent diarrhea, rectal bleeding, weight loss, and fever. Currently no cure is available for Crohn’s disease. 3 ABOUT TREMFYA® (guselkumab) Developed by Johnson & Johnson, TREMFYA ® is the first approved fully-human, dual-acting monoclonal antibody designed to neutralize inflammation at the cellular source by blocking IL-23 and binding to CD64 (a receptor on cells that produce IL-23). Findings for dual-acting are limited to in vitro studies that demonstrate guselkumab binds to CD64, which is expressed on the surface of IL-23 producing cells in an inflammatory monocyte model. The clinical significance of this finding is not known. TREMFYA ® is a prescription medicine approved in the U.S. to treat: TREMFYA ® is approved in Europe, Canada, Japan, and a number of other countries for the treatment of adults with moderate-to-severe plaque psoriasis and for the treatment of adults with active psoriatic arthritis. Johnson & Johnson maintains exclusive worldwide marketing rights to TREMFYA ® . For more information, visit: www.tremfya.com . Please read the full Prescribing Information , including Medication Guide , for TREMFYA® and discuss any questions that you have with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch , or call 1-800-FDA-1088 . Dosage Forms and Strengths : TREMFYA ® is available as 100 mg/mL and 200 mg/2mL for subcutaneous injection and as a 200 mg/20 mL (10 mg/mL) single dose vial for intravenous infusion. ABOUT STELARA® (ustekinumab) STELARA ® (ustekinumab), a human interleukin (IL)-12 and IL-23 antagonist, is a prescription medicine approved in the United States to treat. 13 The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to STELARA ® . Please click to read the full Prescribing Information and Medication Guide for STELARA® and discuss any questions you have with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit https://www.fda.gov/medwatch or call 1-800-FDA-1088. ABOUT JOHNSON & JOHNSON At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com . Follow us at @JNJInnovMed . Janssen Research & Development, LLC, Janssen Scientific Affairs, LLC, Janssen Biotech, Inc., and Janssen-Cilag International NV are Johnson & Johnson companies. 1 Crohn’s & Colitis Foundation. What is Crohn’s disease? Available at: https://www.crohnscolitisfoundation.org/what-is-crohns-disease/causes . Accessed February 2025. 2 Crohn’s & Colitis Foundation. What is Crohn’s disease? Available at: https://www.crohnscolitisfoundation.org/what-is-crohns-disease/causes . Accessed February 2025. 3 Crohn’s & Colitis Foundation. Overview of Crohn’s disease. Available at: https://www.crohnscolitisfoundation.org/what-is-crohns-disease/overview . Accessed March 2025. 4 Atreya R, Abreu MT, Krueger JG, et al. Guselkumab, an IL-23p19 subunit-specific monoclonal antibody, binds CD64+ myeloid cells and potentially neutralizes IL-23 produced from the same cells. Poster presented at: 18th Congress of the European Crohn’s and Colitis Organization (ECCO); March 1-4, 2023; Copenhagen, Denmark. Poster P504. 5 Kreuger JG, Eyerich K, Kuchroo VK. Il-23 past, present, and future: a roadmap to advancing IL-23 science and therapy. Front Immunol. 2024; 15:1331217. doi:10.3389/fimmu.2024.1331217. 6 TREMFYA ® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 7 Skyrizi ® [Prescribing Information]. North Chicago, IL: AbbVie, Inc. 8 Omvoh™ [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company. 9 Panaccione, R, et al. Efficacy and Safety of Subcutaneous Guselkumab Induction Therapy in Patients With Moderately to Severely Active Crohn’s Disease: Results Through Week 48 From the Phase 3 GRAVITI Study. Oral presentation (OP72) at American College of Gastroenterology (ACG) 2024. 10 National Institutes of Health: Clinicaltrials.gov. A study of guselkumab subcutaneous therapy in participants with moderately to severely active Crohn’s disease (GRAVITI). Identifier: NCT05197049. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05197049 . Accessed February 2025. 11 National Institutes of Health: Clinicaltrials.gov. A study of the efficacy and safety of guselkumab in participants with moderately to severely active Crohn’s disease (GALAXI). Identifier: NCT03466411. Available at: https://clinicaltrials.gov/study/NCT03466411 . Accessed February 2025. 12 Danese S, et al. Week 48 efficacy of guselkumab and ustekinumab in Crohn’s disease based on prior response/exposure to biologic therapy: Results from the GALAXI 2 & 3 Phase 3 Studies. Poster presentation (Abstract MP672) at United European Gastroenterology Week (UEGW) 2024. October 2024. 13 STELARA ® Prescribing information. Available at: https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/STELARA-pi.pdf Accessed March 2025. SOURCE: Johnson & Johnson