Peresolimab met the primary efficacy endpoint in patients with refractory rheumatoid arthritis (RA)

Study evaluated a novel approach to treating patients with autoimmune diseases

INDIANAPOLIS, May 18, 2023 /PRNewswire/ -- The New England Journal of Medicine today published detailed results from Eli Lilly and Company's (NYSE: LLY) phase 2a study of peresolimab in rheumatoid arthritis (RA), in which peresolimab met the primary endpoint for efficacy and had similar rates of adverse events between peresolimab and placebo arms. These data represent the first clinical evidence that stimulating the endogenous PD-1 inhibitory pathway could be an effective approach to treat rheumatologic disease. The phase 2a clinical trial (NCT04634253) evaluated the safety and efficacy of peresolimab in adult participants with moderate-to-severe RA who had an inadequate response to prior conventional, biologic or synthetic disease modifying antirheumatic drugs (DMARDs).

"In the study, peresolimab showed meaningful results in refractory RA patients," said Jay Tuttle, Ph.D, study first author and associate vice president, research and development at Lilly. "Refractory patients make up approximately 21% of the RA population1, having tried and failed multiple treatments, and are often hesitant to try new options. While still early, these data signify an important potential new therapeutic approach for RA patients, including both refractory and biologic-naïve patients."

Peresolimab is an investigational humanized immunoglobulin G1 monoclonal antibody that stimulates human programmed cell death protein 1 (PD-1), a checkpoint inhibitory receptor, that may induce physiological immune inhibitory pathways to restore immune homeostasis. RA, a form of rheumatologic disease, is a systemic autoimmune disease characterized by inflammation and progressive destruction of joints.2,3  While several treatment options exist, including the use of oral conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) — such as methotrexate, the current standard of care; and injectable, biological disease-modifying antirheumatic drugs (bDMARDs) — many patients do not reach or maintain their therapeutic goals.4,5,6 There remains a crucial unmet need to provide new treatment options for better overall patient care, particularly for refractory and biologic-experienced patients.

"Lilly is proud to share these results in The New England Journal of Medicine, which reinforce our commitment to discoveries that may transform care for patients. Our ultimate objective in treating immunologic conditions is to achieve not only symptom reduction, but to also induce immune homeostasis and achieve longstanding resolution of disease," said Ajay Nirula, M.D., Ph.D, study senior author and senior vice president, Immunology at Lilly. "These early data for peresolimab in RA reflect our commitment to develop first-in-class therapeutic options for patients."

These data were first presented as a late-breaking abstract at the American College of Rheumatology (ACR) annual Convergence in November 2022. In this phase 2a, double-blind, randomized, placebo-controlled trial, adult patients with moderate-to-severe RA who had an inadequate response to, a loss of response to, or unacceptable side effects with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or to biologic or targeted synthetic DMARDs to receive 700 mg of peresolimab, 300 mg of peresolimab, or placebo intravenously once every 4 weeks. The primary outcome was the change from baseline to week 12 in the Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP). The primary comparison was between the 700-mg group and the placebo group.

At week 12, the change from baseline in the DAS28-CRP was significantly greater in the 700-mg peresolimab group than in the placebo group (least-squares mean change [±SE], −2.09±0.18 vs. −0.99±0.26; difference in change, −1.09 [95% confidence interval, −1.73 to 0.46]; P