A PHASE 2 TRIAL OF PERESOLIMAB FOR ADULTS WITH RHEUMATOID ARTHRITIS

J. Tuttle, E. Drescher, J. A. Simon-Campos, P. Emery, M. Greenwald, A. Kivitz, H. Rha, P. Yachi, C. Kiley, A. NirulaEli Lilly and Company, San Diego Clinical Services, San Diego, United States of America Csolnoky Ferenc Hospital, Rheumatology, Veszprem, Hungary Hospital Agustín O’Horán, Köhler & Milstein Research, Merida, Mexico University of Leeds, NHS Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom Desert Medical Advances, Rheumatology, Palm Desert, United States of America Altoona Center for Clinical Research, Rheumatology, Duncansville, United States of America Eli Lilly and Company, Biomedicines, Indianapolis, United States of America Eli Lilly and Company, Lilly Research Laboratories, San Diego, United States of America  Background Peresolimab is a humanized immunoglobulin G1 monoclonal antibody that stimulates human programmed cell death protein 1 (PD-1). We hypothesized that peresolimab binding to PD-1, a checkpoint inhibitory receptor, could stimulate physiological immune inhibitory pathways to restore immune homeostasis; this represents a novel approach to treating patients with autoimmune or autoinflammatory diseases. Objectives The objective of this study was to evaluate efficacy and safety of peresolimab in adult participants with moderate-to-severe rheumatoid arthritis (RA). Methods A Phase 2a, placebo-controlled, double-blind, randomized clinical trial (NCT04634253) evaluated the efficacy and safety of peresolimab in adult participants with moderately to severely active RA, who had an inadequate response to prior disease modifying drugs, either conventional (csDMARDs), biologic (bDMARDs) or synthetic (tsDMARDS). Treatment comparisons versus placebo were made using mixed effects model for repeated measures (MMRM) and using logistic regression model for continuous and binary endpoints, respectively. Nominal p-values are reported. Missing data for binary endpoints were imputed as non-response. Results One hundred and one patients were randomly assigned 2:1:1 to receive intravenous peresolimab 700 mg (n = 49), 300 mg (n = 25), or placebo (n = 24) Q4W; 98 participants received at least one dose of study treatment and were included in the analysis. Baseline demographics and disease activity were similar among groups. The majority (83.7%) of participants were female. At baseline, the mean (SD) duration of RA was 10.0 (8.0) years, and the mean (SD) DAS28-CRP score was 5.9 (0.85). This trial met its primary endpoint of a significantly greater improvement from baseline at Week 12 in DAS28-CRP score in participants treated with peresolimab vs participants treated with placebo at both tested doses (700 mg [p < 0.001] and 300 mg [p = 0.017], figure 1a). Significant improvements were seen in CDAI between participants treated with either peresolimab dose (figure 1b) relative to placebo, and for ACR20 (p < 0.05) for participants treated with peresolimab 700 mg relative to placebo by Week 12 (table 1). Peresolimab exhibited a safety and tolerability profile that supports further clinical evaluation in immunologic disease. Conclusion Peresolimab, a PD-1 receptor agonist, was superior to placebo at Week 12 for several key endpoints in RA. Safety events were similar between treatment groups. Image/graph: Table 1. Primary and Secondary Efficacy Outcomes at Week 12† Placebo (N=24) Peresolimab 300mg (N=25) Peresolimab 700mg (N=49) Primary endpoint DAS28-CRP CFB LSM (SE) -0.99 (0.261) -1.88 (0.249)* -2.09 (0.184)*** Secondary endpoints ACR20 – n (%) 10 (41.7) 11 (44.0) 35 (71.4)* ACR50 – n (%) 5 (20.8) 5 (20.0) 19 (38.8) ACR70 – n (%) 4 (16.7) 1 (4.0) 10 (20.4) TJC68 CFB LSM (SE) -6.89 (1.846) -12.08 (1.814)* -12.33 (1.288)* SJC66 CFB LSM (SE) -6.18 (1.091) -10.22 (1.082)* -10.49 (0.759)** PGA (VAS) CFB LSM (SE) -25.35 (5.162) -39.07 (5.130) -38.55 (3.576)* PatGA (VAS) CFB LSM (SE) -21.66 (5.390) -24.27 (5.285) -29.67 (3.741) Arthritis Pain (VAS) CFB LSM (SE) -17.94 (5.101) -23.50 (5.000) -31.55 (3.535)* HAQ-DI CFB LSM (SE) -0.41 (0.109) -0.35 (0.107) -0.42 (0.076) hsCRP CFB LSM (SE) 1.34 (3.717) -5.26 (3.626) -0.66 (2.574) CDAI CFB LSM (SE) -13.75 (2.709) -24.06 (2.628)** -25.51 (1.854)*** SDAI CFB LSM (SE) -13.80 (2.664) -25.06 (2.571)** -26.90 (1.880)*** DAS28-CRP = disease activity score-28 for RA with C-reactive protein. ACR = American college of rheumatology. CFB = change from baseline. TJC68 = tender joint count of 68 joints. SJC66 = swollen joint count of 66 joints. VAS = visual analogue scale. PGA = physician’s global assessment of disease activity. PatGA = patient’s global assessment of disease activity. HAQ-DI = health assessment questionnaire – disability index. hsCRP = high sensitivity C-reactive protein. CDAI = clinical disease activity index. SDAI = simplified disease activity index. †Least squares mean (SE) are reported, unless otherwise stated. *p value < 0.05. **p value < 0.01. ***p value < 0.001. Acknowledgements We would like to thank the patients and investigators who participated in the trial. Eli Lilly and Company or its representatives provided data, laboratory, and site monitoring services. Writing assistance was provided by Conor McVeigh, PhD. This work has been presented previously at the following scientific conference: ACR 2022, 14th of November 2022. Funding sources This study was sponsored by Eli Lilly and Company. Disclosure of Interests Jay Tuttle Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Edit Drescher: None declared, Jesús Abraham Simon-Campos: None declared, Paul Emery Paid instructor for: Abbvie, AstraZeneca, BMS, Boehringer Ingelheim, Galapaos, Gilead, Eli Lilly and Company, Novartis, Pfizer, Roche, and Samsung, Consultant of: Abbvie, AstraZeneca, BMS, Boehringer Ingelheim, Galapagos, Gilead, Eli Lilly and Company, Grant/research support from: Abbvie, BMS, Eli Lilly and Company, Novartis, and Samsung, Maria Greenwald Consultant of: Eli Lilly and Company, Alan Kivitz Shareholder of: Pfizer, Sanofi S.A, GSK, Gilead, Novartis, and Amgen, Paid instructor for: Celgene, Merck, Eli Lilly and Company, Novartis, Pfizer, Sanofi S.A, Sanofi Genzyme, Flexion therapeutics, Abbvie, Amgen, Genentech, UCB, Horizon, and GSK, Consultant of: Pfizer, Janssen Pharmaceuticals, Boehringer Ingelheim, Abbvie, Flexion Therapeutics, Gilead, Sanofi A.A, Regeneron, Sun Pharma Advanced Research, and ECOR1, Hyungmin Rha Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Pia Yachi Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Christina Kiley Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ajay Nirula Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company. Keywords: Rheumatoid arthritis, Clinical Trials, Autoantibodies DOI: 10.1136/annrheumdis-2023-eular.3582Citation: , volume 82, supplement 1, year 2023, page 397Session: Original perspectives on old DMARDs and new small molecules in rheumatoid arthritis (Poster Tours)