AnaptysBio announced today that the investigational therapy rosnilimab has achieved positive top line results in the phase 2b clinical trial RENOIR for the treatment of moderate to severe rheumatoid arthritis (RA) patients. Rosnilimab showed statistically significant improvement in the clinical primary endpoint at week 12 of the trial. In addition, at week 14 of the trial, 69% of patients receiving rosnilimab treatment met the criteria of a Clinical Disease Activity Index (CDAI) below 10, indicating a decrease in disease activity (LDA). CDAI is an indicator that uses clinical data to assess the severity of RA disease. Rosnilimab is a monoclonal antibody targeting the immune checkpoint protein PD-1. The company pointed out that it may become the first new mechanism drug for treating RA in 10 years.
The RENOIR trial included a total of 424 patients with moderate to severe RA who received anti rheumatic drugs (cDMARDs) with background routine changes in disease progression, as well as different doses of rosnilimab or placebo treatment. The experimental results showed that rosnilimab reached the primary endpoint of the trial at week 12, with statistically significant differences compared to placebo on the DAS-28 C-reactive protein score (DAS-28 CRP, a composite indicator of patient health status, C-reactive protein levels, and number of swollen and painful joints).
In addition, at week 14 of the trial, 69% of patients treated with rosnilimab met the criteria for CDAI index indicating reduced disease activity (CDAI LDA). Subsequent follow-up data showed that the patient showed signs of maintaining disease remission.
Biomarker studies have shown that rosnilimab rapidly and consistently reduces the number of PD-1 overexpressing T cells, while increasing the number of regulatory T cells, forming a T cell composition favorable for maintaining healthy immune homeostasis. In addition, throughout the entire trial period, the average CRP level of patients treated with rosnilimab decreased by about 50% compared to baseline, demonstrating significant anti-inflammatory effects.
In terms of safety, rosnilimab showed good safety and tolerability in phase 2 clinical trials. No malignant tumors; No major adverse cardiovascular events (MACE); Compared with placebo, there was no increase in severe infections; No allergic shock or systemic hypersensitivity reactions related to rosnilimab; The incidence of injection site reactions is low, similar to placebo.
Rosnilimab is an innovative antibody that targets PD-1. Activated T cells typically express PD-1 receptors on their surface, which have a broad impact on inflammatory diseases such as rheumatoid arthritis and ulcerative colitis. Rosnilimab, as a targeted therapy, aims to deplete PD-1 overexpressing T cells and activate the remaining PD-1 positive T cells to restore the immune system to a steady state. This is expected to lead to specific immunological effects in inflammatory tissues and the periphery, such as reducing T cell proliferation, migration, and cytokine secretion, while lowering plasma cell production and autoantibody levels.
Currently, a phase 2 clinical trial of rosnilimab for the treatment of ulcerative colitis is underway. Dr. Paul Lizzul, Chief Medical Officer of AnaptysBio, stated that these positive clinical data, combined with translational science data, validate the development strategy of treating RA by targeting the PD-1 protein on the surface of T cells. This innovative strategy may also benefit various other autoimmune and inflammatory diseases, including ulcerative colitis.
<Reprinted from WuXi AppTec>
