New York, NY — July 17, 2025 — In a major advance for patients with Crohn's disease, a new study led by researchers at Mount Sinai Health System found that guselkumab, a medication with a mechanism of action that is new to inflammatory bowel disease (IBD) treatment, outperformed an established standard of care in promoting intestinal healing and symptom relief.
These findings from two pivotal phase 3 trials known as GALAXI 2 and 3, published today in The Lancet, provided the basis for the recent Food and Drug Administration approval of guselkumab (brand name Tremfya) for the treatment of moderately to severely active Crohn's disease.
Crohn's disease affects roughly 780,000 people in the United States and often requires a lifetime of management. Despite numerous available biologic medications, many patients fail to achieve sustained remission. Guselkumab blocks the interleukin-23 (IL-23) pathway, a key driver of chronic intestinal inflammation.
"Suboptimal disease control despite the availability of biologic therapies remains a prevalent problem among patients with Crohn's disease," said Bruce E. Sands, MD, MS, the Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine at Mount Sinai and senior author on this paper. "The GALAXI trials were especially impactful as they compared two dosing regimens of guselkumab to both placebo and ustekinumab over a 48-week period. Patients receiving guselkumab showed significantly higher rates of endoscopic healing and deep remission, critical indicators linked to fewer disease flares, hospitalizations, and long-term complications."
Guselkumab is the first biologic shown in identically designed, 48-week, double-blind trials to outperform another leading biologic—ustekinumab, a monoclonal antibody that blocks both IL-12 and IL-23—for key markers of disease remission and gut healing in Crohn's disease. The design allowed for head-to-head comparisons to both placebo and ustekinumab. The studies enrolled 1,048 patients worldwide and randomly assigned participants to one of four groups:
- guselkumab 200 mg intravenously (IV) at weeks 0/4/8, then guselkumab 100 mg subcutaneously (SC) every eight weeks beginning at week 16
- guselkumab IV at weeks 0/4/8, then guselkumab 200 mg every four weeks beginning at week 12
- ustekinumab ~6 mg/kg IV at week 0, then ustekinumab 90 mg SC every eight weeks beginning at week 8
- placebo
Guselkumab demonstrated statistically significant improvements across multiple endpoints, including endoscopic response and deep remission. Safety outcomes, based on adverse events and laboratory findings, were favorable and consistent with the known profile of guselkumab in approved indications.
Beyond symptom control, the therapy's corticosteroid-sparing effect further underscores its clinical value, especially for patients seeking alternatives to long-term steroid use.
The GALAXI 2 and 3 trials were sponsored by Johnson & Johnson and enrolled patients with prior biologic treatment failures.
Dr. Sands, the Chief of Mount Sinai's Dr. Henry D. Janowitz Division of Gastroenterology, is a renowned expert in inflammatory bowel disease. He previously co-authored the pivotal UNITI trial, and was both the lead author and corresponding author on the UNIFI trials. Both of these trials helped establish ustekinumab's place in IBD care. His latest work builds on that legacy, demonstrating not only the effectiveness of IL-23 inhibition but its potential to redefine front-line treatment.
Link to paper: "Efficacy and safety of intravenous induction and subcutaneous maintenance treatment with guselkumab in participants with Crohn's disease: results of two phase 3, randomised, double-blind, placebo-controlled, and head-to-head versus ustekinumab, 48-week trials (GALAXI 2 & 3)." Reference: THELANCET-D-24-08019R1
