S1428 Efficacy and Safety of Subcutaneous Guselkumab Rescue Therapy in Patients With Moderately to Severely Active Crohn’s Disease and Inadequate Response to Ustekinumab: Phase 2 GALAXI 1 Study Long-Term Extension Results

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Introduction: Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that is being evaluated in CD. The GALAXI 1 study (NCT03466411) is a phase 2b study that evaluated GUS in participants (pts) with moderate-to-severe CD. Pts treated with ustekinumab (UST) who met inadequate response criteria during long term extension (LTE) could cross over to GUS 200 mg every 4 weeks subcutaneous (SC). Here, we present efficacy/safety results in pts who received GUS after experiencing an inadequate response to UST in LTE. Methods: Individuals with prior inadequate response or intolerance to UST were excluded from GALAXI 1; however, during the LTE, pts treated with UST ∼6 mg/kg intravenous (IV)→UST 90 mg SC every 8 weeks who met inadequate treatment response criteria (not in clinical response [≥100-point reduction in CDAI score from baseline or CDAI< 150] and CDAI ≥220) between Wks 52-80 of LTE were eligible for a treatment switch to GUS 200 mg every 4 weeks SC, without IV induction. Clinical response and clinical remission were both assessed 16 weeks after treatment switch. Endoscopic response and endoscopic remission were assessed at Wks 96 and 144 (definitions in Figure 1). Safety was assessed through Wk 144. Results: In total, 17 pts treated with UST underwent treatment switch to continuing GUS 200 mg every 4 weeks SC maintenance therapy due to meeting inadequate treatment response criteria between Wks 52-80 of the LTE. Pts who crossed over to GUS exhibited similar baseline demographics and disease characteristics to all GUS LTE pts (Table 1). The proportions of pts achieving clinical response and clinical remission 16 weeks after treatment adjustment from UST to GUS 200 mg SC every 4 weeks were 58.8% and 52.9%, respectively. The proportions of pts achieving endoscopic response and endoscopic remission were 52.9% and 35.3% at study Wk 96, respectively, and were maintained through Wk 144 (Figure 1). Key safety event rates through Wk 144 were consistent with the known safety profile of GUS in approved indications. Conclusion: Among pts who experienced inadequate response to UST in LTE, more than half achieved clinical remission 16 weeks after treatment adjustment to GUS 200 mg SC every 4 weeks and >50% were in endoscopic response at Wk 96. These data suggest pts with an inadequate treatment response to UST may benefit from GUS treatment. Results are limited by small sample size and direct treatment adjustment to GUS SC maintenance dosing without IV induction.Figure 1.: Clinical Response and Remission 16 Weeks After Switch From Ustekinumab to Guselkumab (A), and Endoscopic Outcomes at Study Weeks 96 and 144 Among Participants Who Switched From Ustekinumab to Guselkumab (B). Table 1. - Baseline Demographics and Disease Characteristics Ustekinumab 90 mg SC every 8 weeks → Guselkumab 200 mg SC q4wa N 17 Age in years, mean (SD) 35.4 (10.95) Male, n (%) 12 (70.6%) White, n (%) 15 (88.2%) CD disease duration in years, mean (SD) 10.0 (7.40) CDAI score, mean (SD) 293.0 (41.09) SES-CD score, mean (SD) 13.2 (6.64) Endoscopic disease severity per SES-CD score Moderate (7-16) 9 (52.9%) Severe (>16) 6 (35.3%) Involved GI areas (assessed by central reader) Ileum only 3 (17.6%) Colon only 5 (29.4%) Ileum and Colon 9 (52.9%) SC= subcutaneous; SD= standard deviation; CD= Crohn’s disease; CDAI= Crohn’s disease activity index; SES-CD= Simple Endoscopic Score for Crohn's Disease; GI= gastrointestinal.aParticipants who were randomized to ustekinumab at Week 0 or who switched to ustekinumab at Week 12 and continued SC maintenance dosing of ustekinumab in the maintenance period and treatment-adjusted to guselkumab 200 mg SC every 4 weeks dosing during the long-term extension.

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