POS0307 A PHASE 2 TRIAL OF PERESOLIMAB FOR ADULTS WITH RHEUMATOID ARTHRITIS

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.

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.