S1052 Efficacy and Safety of Subcutaneous Guselkumab Induction Therapy in Patients With Moderately to Severely Active Crohn’s Disease: Results Through Week 48 From the Phase 3 GRAVITI Study

Introduction: Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that was efficacious in phase 3 trials (GALAXI 2/3) of pts with Crohn’s disease (CD) using intravenous (IV) induction and subcutaneous (SC) maintenance. We evaluated the efficacy and safety of GUS SC induction/maintenance in GRAVITI, a phase 3 treat-through trial in patients (pts) with moderately to severely active CD. Methods: Eligible pts had a history of inadequate response or intolerance to oral corticosteroids, AZA, 6-MP, MTX, or biologics (BIO-IR). Randomization was stratified by baseline (BL) CDAI, SES-CD, and BIO-IR status, with 347 pts allocated 1:1:1 to GUS 400mg SC every 4 weeks (x3)→GUS 200mg SC every 4 weeks (N=115), GUS 400mg SC every 4 weeks (x3)→GUS 100mg SC every 8 weeks (N=115), or PBO (N=117). Pts were rescued at week (Wk)16: PBO pts switched to GUS, and GUS pts stayed on GUS per treat-through design (sham rescue). The co-primary endpoints were clinical remission at Wk12 and endoscopic response at Wk12. Other multiplicity-controlled endpoints were clinical remission at Wk24, PRO-2 remission at Wk12, clinical response at Wk12, clinical remission at Wk48, and endoscopic response at Wk48. All endpoints assessed through Wk12 compared the combined GUS 400mg SC treatment arm to PBO; assessments after Wk12 compared each GUS SC maintenance regimen to PBO. All pts who met rescue criteria were considered not to have met efficacy endpoints after Wk16. Safety was assessed through Wk48. Results: BL characteristics were similar across groups (overall mean age, 37.5yrs; mean CD disease duration, 8.0yrs; mean CDAI, 296.9; mean SES-CD, 12.0; BIO-IR, 46.4%). The co-primary and all multiplicity-controlled endpoints were met. GUS 400mg SC induction demonstrated superiority to PBO at Wk12. Both SC maintenance dose regimens were also superior to PBO at Wks 24 and 48 (Figure 1). In prespecified analyses of subpopulations defined by prior biologic history, greater proportions of GUS-treated pts achieved the endpoints than PBO. Key safety event rates per 100 pt years through Wk48 were similar among groups (Table 1). Proportions of GUS-treated pts experiencing ≥1 serious AE or AE leading to discontinuation of study agent were not greater than PBO. The numbers of GUS-treated pts with serious infections or AEs of special interest were low. Conclusion: GRAVITI established the efficacy of GUS SC induction followed by SC maintenance in CD. These results build on the GALAXI 2/3 data and demonstrate that both IV and SC induction are efficacious. Safety findings were consistent with the known safety profile of GUS in approved indications.Figure 1.: Summary of Co-primary and Multiplicity-controlled Endpoints Through Week 48. Table 1. - Safety Summary Through Week 48 Placebo SCa Guselkumab 400 mg SC every 4 weeks → Guselkumab 100 mg SC every 8 weeks Guselkumab 400 mg SC every 4 weeks → Guselkumab 200 mg SC every 4 weeks All Guselkumabb Safety analysis set, N 117 115 115 274 Average duration of follow-up, weeks 30.0 47.0 48.0 44.8 Average exposure, number of administrations 7.1 6.8 11.8 8.5 Total PYs of follow-up, years 67.3 103.5 105.7 235.0 Deaths,c n (%) 0 1 (0.9%) 0 1 (0.4%) Participants with 1 or more: AEs, n (%) 77 (65.8%) 95 (82.6%) 92 (80.0%) 220 (80.3%) Events per 100 PYs follow-up 413.0 307.2 327.2 312.8 SAEs, n (%) 16 (13.7%) 15 (13.0%) 9 (7.8%) 25 (9.1%) Events per 100 PYs follow-up 37.1 15.5 13.2 13.2 AEs leading to DC of study agent, n (%) 10 (8.5%) 4 (3.5%) 3 (2.6%) 8 (2.9%) Events per 100 PYs follow-up 14.9 6.8 2.8 4.7 Serious infections,d n (%) 0 2 (1.7%) 1 (0.9%) 4 (1.5%) Adverse events of special interest, n (%) Active tuberculosis 0 0 0 0 Malignanciese 0 1 (0.9%) 0 1 (0.4%) SC= subcutaneous; PY= participant-years; AE= adverse event; SAE= serious adverse event; DC= discontinuation.aIncludes all placebo participants excluding data after a participant is rescued with guselkumab.bIncludes all participants initially randomized to guselkumab at Week 0, and placebo participants who were rescued with guselkumab; only data after a participant crossed over to guselkumab is included.cFatal gunshot wound (non-suicidal).dInfections were defined as any adverse event which was coded to the MedDRA system organ class 'Infections and infestations'.eBasal cell carcinoma of skin; participant continued in the study.Note: Participants are counted only once for any given event under specific column, regardless of the number of times they actually experienced the event.Adverse events are coded using MedDRA Version 26.0.

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