GALAXI 2 & 3: Guselkumab Superior to Ustekinumab for Crohn's Disease

Guselkumab therapy demonstrated statistical superiority to placebo and ustekinumab among a population with moderately to severely active Crohn’s disease, according to late-breaking phase 3 data presented at Digestive Disease Week (DDW) 2024.¹

These results were reported from the identical, 48-week, randomized, double-blind, active-comparator GALAXI 2 (n = 508) & GALXI 3 (n = 513) registrational trials, assessing the efficacy and safety of guselkumab, the first fully human IL-23 inhibitor.

Each study demonstrated the superiority of both subcutaneous maintenance doses of guselkumab 200 mg every 4 weeks (Q4W) and 100 mg every 8 weeks (Q8W) over placebo, indicating the drug’s achievement of greater clinical response and remission. In GALAXI 2 & 3, both dose cohorts had statistically significant and clinically meaningful differences on all prespecified pooled endoscopic endpoints compared with ustekinumab.

“These results are promising for those who continue to experience persistent and debilitating symptoms and offer the possibility of guselkumab as a future-first advanced therapy or after failure of other advanced therapies that may deliver the lasting remission patients deserve to relieve the burden of disease,” lead study investigator Remo Panaccione, MD, a professor of medicine at the University of Calgary, said in a statement.²

Crohn’s disease, alongside ulcerative colitis, makes up the two primary forms of inflammatory bowel disease (IBD) that affect an estimated 3 million people in the United States.³ Symptoms of Crohn’s can include abdominal pain and tenderness, frequent diarrhea, and rectal bleeding—no cure currently exists for Crohn’s disease.

Results on the clinical endpoint from GALAXI 2 & 3 showed higher percentages of participants with Crohn’s disease treated with guselkumab 200 mg Q4W (70.3%; P = .058) or guselkumab 100 mg Q8W (65.4%; P = .512) achieved clinical remission versus ustekinumab (62.9%).

Meanwhile, endoscopic endpoints showed higher rates of participants in the guselkumab 200 mg Q4W (47.3%; P <.001) or guselkumab 100 mg Q8W (41.6%; P = .049) achieved clinical remission and endoscopic response versus ustekinumab (33.7%). Additional results showed that 37.2% (P = .001) and 33.2% (P = .024) of the guselkumab cohorts achieved endoscopic remission versus 24.7% of the ustekinumab cohort.

Guselkumab’s safety profile remained consistent with the approved indications of moderate to severe plaque psoriasis and active psoriatic arthritis (PsA). At week 48, the number of patients with ≥1 adverse event, ≥1 serious adverse event, and an event leading to discontinuation were similar across treatment cohorts, including guselkumab, placebo, or ustekinumab.

“The Phase 3 GALAXI program, comprised of two rigorous, double-blind studies with secondary endpoints comparing TREMFYA to ustekinumab, reiterate our dedication to addressing the needs of patients with Crohn's disease and our deep scientific expertise in inflammatory bowel disease and focused innovation in the IL-23 pathway," David Lee, MD, PhD, global therapeutic area head of immunology at Johnson & Johnson Innovative Medicine, added in a statement.

Johnson & Johnson has previously announced the submission of a supplemental Biologics License Application to the US Food and Drug Administration (FDA) seeking approval for guselkumab in treating moderately to severely active ulcerative colitis.

References

1. _{Panaccione R, Danese S, Feagan BG, D’Haens G, Afzali A, Reinisch W, Panés J, Rubin DT, Andrews JM, et al. Efficacy and Safety of Guselkumab Therapy in Patients with Moderately to Severely Active Crohn’s Disease: Results of the GALAXI 2 & 3 Phase 3 Studies. Lecture presented at Digestive Disease Week 2024, May 18 - 21, 2024.}
2. _{Johnson & Johnson. Johnson & Johnson submits Supplemental Biologics License Application to U.S. FDA seeking approval of Tremfya®(guselkumab) for the treatment of adults with moderately to severely active ulcerative colitis (2024). May 21, 2024. Accessed May 21, 2024.}
3. _{Seyedian SS, Nokhostin F, Malamir MD. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. J Med Life. 2019;12(2):113-122. doi:10.25122/jml-2018-0075}