SUMMARY  

• The safety and efficacy of TREMFYA in adult patients with moderately to severely active Crohn's disease were evaluated through a phase 2/3 randomized, double-blind, placebo- and active-controlled (ustekinumab) program (GALAXI).¹
• In the GALAXI program, patients must have discontinued biologic therapy prior to the first dose of study intervention.
• During the long-term extension (LTE) of the phase 2b study (GALAXI 1), patients treated with ustekinumab who lost response could switch directly from ustekinumab 90 mg subcutaneous (SC) every 8 weeks to TREMFYA 200 mg SC every 4 weeks, without TREMFYA intravenous (IV) induction.
• Summarized below are results from the GALAXI 1 study. Please note, although the summary reports the outcomes of a subgroup of patients who switched from ustekinumab treatment to TREMFYA during the LTE, the results are limited by small sample size and direct treatment adjustment to TREMFYA SC maintenance dosing without IV induction.

Clinical Data

Clinical Protocol

• Patients included in the GALAXI phase 2b/3 program were those who had an inadequate response or intolerance to previous conventional therapies (oral corticosteroids, immunomodulators [6-mercaptopurine, azathioprine, or methotrexate]) or biologics (tumor-necrosis factor antagonists, vedolizumab).² 
• The following medications/therapies must have been discontinued before the first dose of study intervention:
  • Anti-TNF therapy (eg, infliximab, etanercept, certolizumab pegol, adalimumab, golimumab) received within 8 weeks of baseline.
  • Vedolizumab received within 12 weeks of baseline.
  • Ustekinumab received within 16 weeks of baseline.
  • Please note; a shorter washout duration for anti-TNF agents, ustekinumab or vedolizumab is acceptable if undetectable drug levels of the biologic can be demonstrated.
• Patients were excluded if previously received a biologic agent targeting IL-12/23 or IL-23, including but not limited to briakinumab, brazikumab, guselkumab, mirikizumab, and risankizumab, EXCEPT:
  • Patients who have had exposure to ustekinumab at its approved labeled dosage AND have met the required washout criterion AND have not demonstrated failure or intolerance to ustekinumab. These patients were not excluded from this protocol provided that other inclusion criteria have been satisfied and no other exclusion criteria are met.

Clinical Data

• During the GALAXI 1 study, patients were randomized 1:1:1:1:1 to the following treatment arms:¹ 
  • TREMFYA 200 mg IV every 4 weeks (q4w) followed by TREMFYA 100 mg SC every 8 weeks (q8w; N=61 for the maintenance phase; N=48 for the LTE).
  • TREMFYA 600 mg IV q4w followed by TREMFYA 200 mg SC q4w (N=63 for the maintenance phase; N=54 for the LTE).
  • TREMFYA 1200mg IV q4w followed by TREMFYA 200 mg SC q4w (N=61 for the maintenance phase; N=49 for the LTE).
  • Ustekinumab ~6 mg/kg IV at Week 0 followed by ustekinumab 90 mg SC q8w (N=63 for the maintenance phase; N=48 for the LTE).
  • Placebo (N=61; placebo non-responder were eligible to crossover to ustekinumab treatment at Week 12).
• As described above, during the GALAXI program, patients with prior inadequate response or intolerance to ustekinumab were excluded. However, during the phase 2b study (GALAXI 1) LTE (weeks 52-80), patients treated with ustekinumab who lost response were eligible to switch directly from ustekinumab 90 mg SC q8w to TREMFYA 200 mg SC q4w without TREMFYA IV induction.
  • An inadequate response was defined as not in clinical response (≥100-point reduction in Crohn’s Disease Activity Index [CDAI] score from baseline or CDAI <150) and CDAI ≥220.
• A total of 17 patients treated with ustekinumab who lost response during the LTE were switched to TREMFYA 200 mg SC q4w maintenance
• Clinical response (≥100-point reduction from baseline in CDAI score or CDAI <150) and clinical remission (CDAI <150) were assessed 16 weeks after treatment adjustment.
• Endoscopic response and endoscopic remission were assessed at LTE Weeks 96 and 144 (approximately 1 and 2 years after treatment adjustment, respectively):
  • Endoscopic response: ≥50% improvement from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) or SES-CD ≤2.
  • Endoscopic remission: SES-CD ≤4 and at least a 2-point reduction from baseline and no subscore greater than 1 in any individual component.
• Clinical outcomes 16 weeks after treatment switch in patients who switched from ustekinumab to TREMFYA 200 mg SC every 4 weeks were consistent with those in the subpopulation with a history of inadequate response or intolerance to biologic therapy (BIO-IR) 12 weeks after IV induction with TREMFYA 200 mg IV every 4 weeks. See Table: Clinical Outcomes 16 Weeks After Treatment Switching.

• Endoscopic response and remission approximately one and two years after treatment switch (study weeks 96 and 144, respectively) were consistent with the one- and two-year endoscopic response and remission results (study weeks 48 and 96, respectively) in BIO-IR patients who received TREMFYA throughout LTE. See Table: Endoscopic Outcomes During the Long-term Extension.

Safety¹ 

• There were no adverse events that led to that lead to discontinuation in the subgroup of patients who switched from ustekinumab to TREMFYA.
• There was 1 injection-site reaction that was reported
  • The patient recovered and continued the study.
• 1 serious adverse event was reported
  • The patient experienced irritable bowel syndrome but recovered and continued the study.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 04 November 2024.