GALAXI Findings and Guselkumab’s Role in Crohn’s Disease Care, with Bruce Sands, MD

Despite recent therapeutic advances, substantial unmet needs remain in moderate to severe Crohn’s disease (CD), particularly for patients who are refractory to current biologics or require therapies with improved safety and durability. As the treatment landscape grows more complex—with anti-TNFs, integrin blockers, IL-12/23 inhibitors, JAK inhibitors, and now selective IL-23 blockers—clinicians continue to seek agents that offer reliable efficacy, durable remission, and broad applicability across patient populations.

New data from the GALAXI trial program evaluating guselkumab (Tremfya), a selective IL-23p19 inhibitor, are providing clinicians with critical insight into how this therapy may fit into evolving care paradigms.

“There are many unmet needs in IBD, especially in Crohn's disease,” senior author Bruce Sands, MD, Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine at Mount Sinai, explained to HCPLive, describing the different mechanisms of action of existing therapies and the potential benefits of newer IL-23 inhibitors like mirikizumab, risankizumab, and guselkumab.

Approved by the US Food and Drug Administration (FDA) for CD in March 2025, the decision marked guselkumab’s fourth indication in the US following initial approval from the FDA in 2017 for treatment of moderate-to-severe plaque psoriasis and subsequent indications for active psoriatic arthritis and moderately to severely active ulcerative colitis in 2020 and 2024, respectively.

Findings from the phase 3 GALAXI 2 and 3 trials, described by Sands as being “gold standard trials,” provided the basis for the FDA approval of guselkumab for CD.

“This was really one of the most rigorously performed study programs ever, because it was double blinded, double dummy, but also included not only a placebo comparator, but an active comparator using an agent that we know to be effective in Crohn's disease, namely ustekinumab,” Sands explained. “We have comparison to placebo, comparison to an effective therapy, ustekinumab, all in a blinded fashion, and over 48 weeks. The other innovative thing is the treat through design, so what you see at the end is what you really started with at the beginning.”

The identically designed, 48-week, double-blind trials enrolled 1048 patients worldwide and randomly assigned them to 1 of 4 groups:

• Guselkumab 200 mg intravenously (IV) at weeks 0/4/8, then guselkumab 100 mg subcutaneously (SC) every 8 weeks beginning at week 16
• Guselkumab IV at weeks 0/4/8, then guselkumab 200 mg every 4 weeks beginning at week 12
• Ustekinumab ~6 mg/kg IV at week 0, then ustekinumab 90 mg SC every 8 weeks beginning at week 8
• Placebo

In GALAXI-2, both guselkumab regimens were superior to placebo for the endpoint of clinical response at week 12 and clinical remission at week 48, which was observed in 55% of participants in the guselkumab 200 mg group, 49% of the guselkumab 100 mg group, and 12% of the placebo group. In GALAXI-3, the endpoint was observed in 48% of participants in the guselkumab 200 mg group, 47% of the guselkumab 100 mg group, and 13% of the placebo group.

Similarly, both guselkumab regimens were superior to placebo for the endpoint of clinical response at week 12 and endoscopic response at week 48 in GALAXI-2, observed in 38% of participants in the guselkumab 200 mg group, 39% of the guselkumab 100 mg group, and 5% of the placebo group. In GALAXI-3, the endpoint was observed in 36% of participants in the guselkumab 200 mg group, 34% of the guselkumab 100 mg group, and 6% of the placebo group.

“The efficacy is not just with regard to symptoms, but also with regard to endoscopic response, so we have both subjective and objective response and even remission,” Sands said. “We see it being effective in a range of patients who are naive to biologic therapies or advanced therapies, as well as patients who are refractory to other advanced therapies, so we can think of using it across the spectrum of disease.”

Of note, safety outcomes, based on adverse events and laboratory findings, were favorable and consistent with the known profile of guselkumab in approved indications.

“[Taken together, this] means we have a safe and effective therapy with convenient dosing regimens for patients with moderately, severely, moderately to severely Crohn's disease across the spectrum of disease,” Sands said.

Editors’ note: Sands has relevant disclosures with AbbVie, Alimentiv, Amgen, Bristol Myers Squibb, AstraZeneca, Ferring, and others.

References

1. Panaccione R, Feagan BG, Afzali A, et al. Efficacy and safety of intravenous induction and subcutaneous maintenance therapy with guselkumab for patients with Crohn's disease (GALAXI-2 and GALAXI-3): 48-week results from two phase 3, randomised, placebo and active comparator-controlled, double-blind, triple-dummy trials. The Lancet. doi:10.1016/S0140-6736(25)00681-6

2. Campbell P. FDA Approves Guselkumab (Tremfya) For Crohn Disease. HCPLive. March 20, 2025. Accessed July 28, 2025. https://www.hcplive.com/view/fda-approves-guselkumab-tremfya-for-crohn-disease