S1429 Efficacy of Guselkumab in Moderately to Severely Active Crohn’s Disease According to Induction Clinical Response Status: Week 48 Results from the GALAXI 2 & 3 Phase 3 Trials

Introduction: GALAXI 2 & 3 (G2/3) (NCT03466411) are identical 48-week (wk), randomized, double-blind, double-dummy, placebo (PBO)- and active-comparator–controlled registrational trials assessing the efficacy and safety of guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, in participants (pts) with moderately to severely active Crohn’s disease. G2/3 used a treat-through design, where GUS pts were assigned to 1 of 2 intravenous (IV) induction→SC maintenance regimens at Wk0, and maintenance treatment was not influenced by their clinical response status after induction (Wk12). We report pooled exploratory analyses of clinical and endoscopic endpoints at Wk48 among pts with and without a Wk12 clinical response to GUS induction therapy. Methods: Pts were randomized 2:2:2:1 to the following induction→maintenance regimens: GUS 200mg IV every 4 weeks (x3)→100mg SC every 8 weeks, GUS 200mg IV every 4 weeks (x3)→200mg SC every 4 weeks, ustekinumab ∼6mg/kg IV→90mg SC every 8 weeks, or PBO. These analyses of pooled G2/3 data for GUS recipients were conducted post hoc; comparable analyses of the individual trials were prespecified. Clinical response was defined as a ≥100-point reduction from baseline in CDAI score or CDAI< 150. Wk48 endpoints included clinical remission (CDAI< 150), endoscopic response (≥50% improvement in SES-CD or SES-CD≤2) and PRO-2 remission (patient-reported CDAI components of abdominal pain and stool frequency [mean daily scores ≤1 and ≤3, respectively] with no worsening from baseline). Results: The pooled analyses included 268 pts who received GUS 200mg IV→100mg SC every 8 weeks and 278 who received GUS 200mg IV→200mg SC every 4 weeks. Combined, approximately 66% were in clinical response to GUS induction at Wk12. Clinical remission rates at Wk48 were 77.0–83.5% among Wk12 GUS induction clinical responders and 55.6–58.3% among pts not in clinical response at Wk12, and PRO-2 remission rates were 71.3–75.8% and 46.7–49.0%, respectively (Table 1). Endoscopic response rates at Wk48 were 58.4–60.4% and 36.7–47.9% among induction responders and non-responders, respectively (Table 1). Conclusion: Among the subset who achieved clinical response at Wk12, most pts in both GUS maintenance dose groups went on to achieve clinical remission, PRO-2 remission, or endoscopic response at Wk48. Moreover, efficacy at Wk48 with both GUS maintenance doses was also observed in pts not in clinical response at Wk12, suggesting a benefit of continued treatment with GUS even if clinical response is not achieved at Wk12. Table 1. - Efficacy Outcomes at Week 48 in GALAXI 2 & 3 Participants with and without a Clinical Response to 12-Week Induction Treatment with Guselkumab (Week 12 Treated Primary Analysis Set)a Week 48 Endpoint, n (%)c GUS Induction Respondersb GUS Induction Non-respondersb GUS 200mg IV→ 100mg SC every 8 weeks (N=178) GUS 200mg IV→ 200mg SC every 4 weeks (N=182) GUS 200mg IV→ 100mg SC every 8 weeks (N=90) GUS 200mg IV→ 200mg SC every 4 weeks (N=96) Clinical Remissiond 137 (77.0%) 152 (83.5%) 50 (55.6%) 56 (58.3%) Endoscopic Responsee 104 (58.4%) 110 (60.4%) 33 (36.7%) 46 (47.9%) PRO-2 Remissionf 127 (71.3%) 138 (75.8%) 42 (46.7%) 47 (49.0%) AE=adverse event; AP =abdominal pain; CD=Crohn’s disease; CDAI=Crohn’s disease activity index; COVID-19=coronavirus disease 2019; GUS=guselkumab; IV=intravenous; PRO 2=patient-reported CDAI components of abdominal pain and stool frequency; pts=participants; every 4 weeks=every 4 weeks; every 8 weeks=every 8 weeks; SC=subcutaneous; SES-CD=Simple Endoscopic Score for Crohn’s Disease; SF=stool frequency.aIncludes pts from the primary analysis set, defined as all randomized pts who received ≥1 (partial or complete) dose of study intervention and had a screening SES-CD score ≥6 (or ≥4 for pts with isolated ileal disease), who were treated at Week 12 and did not have a CD-related surgery; prohibited change in concomitant CD medication; or discontinue study agent due to lack of efficacy, an AE of worsening CD, or for any other reason other than COVID-19-related reasons or regional crisis in Ukraine and Russia prior to Week 12.bResponder and non-responder to GUS induction treatment defined as achieving a clinical response at Week 12 (≥100 point reduction from baseline in CDAI or CDAI< 150) or not, respectively.cPts with CD-related surgery; prohibited change in concomitant CD medication; or who discontinued study agent due to lack of efficacy, AE of worsening CD or Week 20/24 nonresponse, or discontinued study agent for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint were considered not to have met the endpoint criteria. Pts who had discontinued study agent due to COVID-19 related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available, to determine responder and non-responder status from that timepoint onwards. Missing data imputation: After accounting for these scenarios, pts with insufficient data to calculate the outcome measure at the designated analysis timepoint were considered not to have achieved the endpoint at that timepoint.dCDAI remission defined as CDAI score < 150.eEndoscopic response defined as ≥50% improvement from baseline in SES-CD score or SES-CD score ≤2.fPRO-2 remission is defined as AP mean daily score ≤1 and SF mean daily score ≤3, and no worsening of AP or SF from baseline.

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