SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• GALAXI 2 & 3 are two identical 48-week, phase 3, randomized, double-blind, placebo (PBO)-and active-controlled, treat-through studies that evaluated the efficacy and safety of TREMFYA (intravenous [IV] induction followed by subcutaneous [SC] maintenance) in adults with moderately to severely active Crohn’s disease (CD).^1,2
• GRAVITI is a phase 3, randomized, double-blind, PBO-controlled, treat-through clinical study in adult patients with moderately to severely active CD that evaluated the efficacy and safety of TREMFYA (SC induction followed by SC maintenance).³
• Clinical outcomes based on disease location from the pooled GALAXI 2 and 3 studies and GRAVITI study are summarized below.^4-9

CLINICAL DATA

Pooled GALAXI 2 & 3 Studies

Results

Clinical Outcomes Based on Disease Location

• Clinical outcomes from the pooled GALAXI 2 & 3 studies bases on disease location are summarized in Table⁵: See Tables: Co-primary Endpoints for TREMFYA vs PBO and Table: Clinical Remission and Endoscopic Response for TREMFYA vs UST.

Phase 3 SC Induction Study in CD: GRAVITI

• GRAVITI is phase 3, randomized, double-blind, PBO-controlled, parallel-group, multicenter, treat-through study.³
• Enrolled patients had a history of inadequate response or intolerance to oral corticosteroids (CSs), azathioprine, 6-mercaptopurine, methotrexate, or biologics (infliximab, adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars for these therapies).
• A total of 347 patients were randomized 1:1:1 to receive the following:
  • TREMFYA 400 mg SC at weeks 0, 4, and 8 followed by 200 mg SC every 4 weeks (q4w; n=115)
  • TREMFYA 400 mg SC at weeks 0, 4, and 8 followed by 100 mg SC every 8 weeks (q8w; n=115)
  • PBO (n=117).

Results

Efficacy by Disease Location

• Predefined subgroup analyses were conducted based on the disease location (ileum, colon, or both).
• Significantly greater proportions of patients treated with TREMFYA vs PBO achieved the co-primary endpoints (clinical remission at week 12 and endoscopic response at week 12). Additionally, in the subgroup analyses based on disease location, numerically greater proportions of patients treated with TREMFYA vs PBO were in clinical remission and endoscopic response at week 12.⁴ For details, see Table: Clinical Remission at Week 12 by Disease Location.

• For endoscopic response at week 12, see Table: Endoscopic Response at Week 12 by Disease Location.

Pooled Analysis of GALAXI and GRAVITI Studies

Sands et al (2025)⁷ conducted a pooled analysis to evaluate the efficacy of TREMFYA in patients with moderately to severely active CD through week 12, stratified by baseline disease characteristics, using data from the GALAXI (IV induction) and GRAVITI (SC induction) studies.

Study Design/Methods

• The analysis included patients from GALAXI 2 and GALAXI 3 (TREMFYA 200 mg IV q4w, n=582; PBO IV q4w, n=148) and GRAVITI (TREMFYA 400 mg SC q4w, n=230; PBO SC q4w, n=117).
• Clinical remission (Crohn’s disease activity index [CDAI] <150) and endoscopic response (≥50% improvement from baseline Simple Endoscopic Score for Crohn’s Disease [SES-CD] were assessed at week 12 across predefined subgroups based on the baseline disease location (ileum, colon, or both).

Results

• Clinical remission and endoscopic response at week 12 based on the disease location are summarized. See Table: Clinical Remission at Week 12 by Disease Location and Table: Endoscopic Response at Week 12 by Disease Location.

Post Hoc Analysis of GRAVITI and GALAXI Studies

GALAXI and GRAVITI Studies

Richards et al (2025)⁶ conducted a post hoc analysis to evaluate the endoscopic outcomes between TREMFYA and ustekinumab (UST) across ileal, ileocolonic, and colonic regions using data from the phase 3 GRAVITI and GALAXI 2 & 3 studies.

Study Design/Methods

• Endoscopic clustering was performed using baseline segmental SES-CD values across 5 intestinal regions: terminal ileum, right colon, transverse colon, left/sigmoid colon, and rectum from cohort 1 (n=1233; from the GALAXI 1, GALAXI 2, and GRAVITI studies) and cohort 2 (n=525; from the GALAXI 3 study).
• Patients from the GALAXI 2 and GALAXI 3 studies were pooled to assess the endoscopic outcomes at weeks 12 and 48 for the TREMFYA and UST groups.

Results

• Seven CD endoscopic subtypes such as ileum only, ileum dominant, right colon dominant, mid-colon, colonic, ileocolonic, and rectum dominant were identified.
• Patient clusters were used with baseline stricturing data (SES-CD narrowing >0) to consolidate groups with differential treatment effects.
• In total, TREMFYA showed higher endoscopic remission rates than UST at weeks 12 and 48. See Table: Endoscopic Remission Rates for TREMFYA vs Ustekinumab Across Ileal, Ileocolonic, and Colonic Regions.

• At week 12, patients in groups 2 and 3 with baseline stricturing who were TREMFYA endoscopic responders (and not UST responders) demonstrated a greater reduction in intestinal narrowing, leading to a 21% decrease in total SES-CD compared with a 5% reduction among TREMFYA nonresponders.

Molecular Analyses

GALAXI 2 and 3 Studies

Richard et al (2025)⁸ conducted an analysis to characterize the molecular differentiation of TREMFYA compared with UST in patients with isolated ileal CD from the pooled GALAXI 2 & 3 studies using serum pharmacodynamic markers and tissue transcriptomics.⁸

Study Design/Methods

• Serum biomarkers were measured in a subset of 50 patients per group at weeks, 0, 4, and 12.
• Matched ileal and rectal biopsies were evaluated at weeks 0, 12, and 48 from a subset of 344 patients representative of the full study population.
• Transcriptional profiling was performed using bulk RNA sequencing and evaluated using transcriptional modules.
• Treatment effects were analyzed using molecularly inflamed samples (biopsy molecular inflammation score [bMIS]>0) from segments with SES-CD >0 at baseline.
• Serum proteins and transcriptional modules were analyzed for differential expression across disease subtypes defined at screening: isolated ileal, isolated colonic, and ileocolonic CD.

Results

• In patients with isolated ileal disease, TREMFYA reduced the serum levels of IL-22, IL-17A, and interferon gamma (IFN-γ) at week 12, whereas UST reduced the serum level of only IFN-γ.
• In ileal tissue, TREMFYA significantly altered inflammatory modules at weeks 12 and 48, including reductions in neutrophil, inflamed epithelium, IL-23/Th17, and inflammatory fibroblast biology, compared with UST, which significantly reduced only the neutrophil, plasma cell, and macrophage modules at week 48.
• In patients with isolated colonic or ileocolonic disease, both TREMFYA and UST reduced IL-23-dependent serum proteins toward levels observed in healthy control sera.
• In rectal tissue, both treatments significantly altered key inflammatory transcriptional modules at weeks 12 and 48.
• Overall, greater molecular effects of TREMFYA vs UST were observed in ileal tissue at weeks 12 and 48 in transcriptional modules associated with reduced disease-related features and restoration of epithelial health.

GALAXI and GRAVITI Studies

Sohn et al (2025)⁹ conducted an analysis to compare tissue molecular effects of TREMFYA SC vs TREMFYA IV induction using data from the GALAXI and GRAVITI studies.

Study Design/Methods

• Serum IL-22 were measured at weeks 0 and 12 using a high-sensitivity assay, and changes in protein abundance were evaluated at week 0 and week 12 for the following groups: GRAVITI (TREMFYA 400 mg SC q4w induction [n=202] vs PBO [n=86]); GALAXI (TREMFYA 200 mg IV q4w induction [n=50] vs PBO [n=50]; and independent healthy control sera [n=30]).
• Transcriptional profiling of ileum and rectum segments was performed at weeks 0 and 12 using bulk RNA sequencing in GRAVITI patients (n=277) randomized to TREMFYA SC or PBO and a subset of GALAXI patients (n=259) randomized to TREMFYA IV or PBO.
• Gene co-expression modules were analyzed for differential expression in the bulk RNA sequencing dataset from ileum and rectum segments, including patients stratified by prior inadequate response or intolerance to biologics.
• Tissue treatment effects were assessed in inflamed samples (defined as those with bMIS >5) from segments with SES-CD >0 at baseline.

Results

• At week 12, TREMFYA SC and IV induction resulted in similar reductions in serum IL-22 (SC: -0.93 logFC; IV: -1.10 logFC; P<0.05), consistent with previously reported decreases in IFN-γ, IL-17A, CRP, and fecal calprotectin (P<0.05).
• Changes in gene module in tissue observed with TREMFYA SC 400 mg q4w induction at week 12 were significantly correlated with those observed with TREMFYA IV 200 mg q4w (R=0.97 in ileum; R=0.93 in rectum; P<0.05).
• Similar PD and molecular treatment effects were observed in patients stratified by prior biologic exposure.
• In both ileum and rectum, TREMFYA SC and IV induction reduced key inflammatory transcriptional modules, including plasma cell, inflammatory epithelial, neutrophil, and IL-23/T helper 17 biology (false discovery rate <0.05) at week 12.
• Similar reductions in the tissue gene expression of IL-22, IL-17A, and IFN-γ were observed at week 12, with levels approaching those of non-inflammatory bowel disease controls.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 19 February 2026.