S1143 The Anti-TL1A Antibody PRA023 Demonstrated Proof-of-Concept in Crohn’s Disease: Phase 2a APOLLO-CD Study Results

Introduction: Tumor necrosis factor–like cytokine 1A (TL1A) is regulator of inflammation and fibrosis. PRA023 is an anti-TL1A monoclonal antibody in development for inflammatory/fibrotic diseases with a companion genetic-based diagnostic test (Dx). This phase 2a, multicenter, open-label study aimed to assess the efficacy and safety of PRA023 as induction treatment in adults with moderately to severely active Crohn’s Disease (CD). Methods: Key eligibility criteria included Crohn’s Disease Activity Index (CDAI) ≥220 and ≤450 with centrally read Simple Endoscopic Score (SES)-CD of ≥6 (≥4 isolated ileal disease) and a history of insufficient/loss of response and/or intolerance to conventional and/or approved biologic therapies. Eligible patients received intravenous PRA023 1000 mg on Day 1, 500 mg at weeks 2, 6, and 10. The primary endpoint was endoscopic response (reduction in SES-CD of ≥50%) at week 12. Historical placebo control rates were used as a reference for the null hypothesis. An exploratory efficacy assessment in a subpopulation identified by the Dx was included. Results: Of the 55 patients enrolled, 53 (96.4%) completed the 12-week induction period. Patients had a high rate of prior biologic exposure (70.9%) and a mean (SD) disease duration of 10.3 (9.3) years (Table 1). A significantly greater proportion of patients receiving PRA023 achieved endoscopic response (26% PRA023 vs 12% historical placebo estimate, P=0.002) and clinical remission (CDAI < 150 points; 49% PRA023 vs 16% historical placebo estimate, P< 0.001). Efficacy was observed in biologic-exposed patients (33% endoscopic response and 38.5% clinical remission), while concurrent steroid or immunosuppressant use did not impact efficacy. Significant reductions from baseline in C-reactive protein and fecal calprotectin were observed at all time points (Figure 1). Although the pre-specified Dx algorithm provided only limited additional benefit in clinical responses, an alternative CD-specific algorithm demonstrated enhanced performance across both clinical (12/21 [57%] remission) and endoscopic (9/20 [45%] response) outcomes. No serious/severe adverse events were deemed as study drug–related. Conclusion: This phase 2a study demonstrated robust proof-of-concept for PRA023’s efficacy in moderately to severely active CD with favorable tolerability. Patient selection using prespecified genetic markers showed promising results. Placebo-controlled clinical trials will be conducted to confirm these findings. Table 1. - Demographics and Baseline Characteristics PRA023 (N=55) Age, y 39.1±15.7 Female, No. (%) 21 (38.2) Weight, kg 77.6±20.6 Geographic region, No. (%) North America 33 (60) Eastern Europe 13 (23.6) Western Europe 7 (12.7) Rest of world (Australia) 2 (3.6) Duration of disease, y 10.3±9.3 Extent of disease, No. (%) Ileal 8 (14.5) Colonic 15 (27.3) Ileocolonic 32 (58.2) Baseline CDAI Score 317.9±67.2 Baseline SES-CD 13.4±6.7 Concomitant immunosuppressant use, No. (%) 8 (14.5) Concomitant corticosteroid use, No. (%) 22 (40) Prior biologics exposure, No. (%) 0 16 (29.1) 1 10 (18.2) 2 10 (18.2) ≥3 19 (34.5) Plus-minus values are means ±SD.Abbreviations: CDAI, Crohn’s Disease Activity Index; SES-CD, Simple Endoscopic Score for Crohn's Disease. Figure 1.: Change Over Time in Geometric Mean Values ± SE for (A) High-Sensitivity C-Reactive Protein (hsCRP) and (B) Fecal Calprotectin Nominal p values, *P<0.05, **P<0.01, ***P<0.001.