Efficacy and safety of E6011 in RA patients with inadequate response to methotrexate

Data from a phase 2 study suggests that use of E6011, a new human anti-fractalkine monoclonal antibody, may be beneficial for rheumatoid arthritis (RA) patients with an inadequate response to methotrexate. E6011 led to significant clinical improvements, especially in those with higher CD16+ monocytes. In addition to its efficacy, E6011 was overall well-tolerated in Japanese RA patients naïve to methotrexate.

Fractalkine (CX3CL1) is a chemokine that regulates chemotaxis and cell adhesion of leukocytes expressing the cognate receptor, CX3CR1, during their migration. The serum level of fractalkine is elevated in patients with RA and is linked to disease activity. Peripheral blood CD16+ monocytes and a subset of T cells express CX3CR1, while fractalkine is expressed on fibroblast-like synoviocytes and endothelial cells in the synovial tissue of patients with RA [1].

Dr Yoshiya Tanaka et al. (University of Occupational and Environmental Health, Japan) evaluated the efficacy and safety of E6011 in RA compared with placebo [2]. This 24-week phase 2 study was set up as a double-blind, placebo-controlled study with 4 treatment arms. A total of 190 patients were randomised to receive E6011 subcutaneously (100 mg/day, n=28; 200 mg/day, n=54; 400/200 mg/day, n=54), or placebo (n=54). In the E6011 lower-dose and placebo groups, subjects received treatment at weeks 0, 1, 2, and every 2 weeks thereafter. In the E6011 400/200 mg group, subjects received 400 mg at weeks 0, 1, 2, 4, 6, 8, 10 followed by 200 mg every 2 weeks subsequently.

At week 24, the ACR20 response rate was significantly higher in patients receiving the two higher doses E6011 compared with placebo (53.7% for 200 mg, 57.4% for 400/200 mg vs 35.2% for placebo). Differences in the ACR20 response rate at week 12 were statistically not significant between the 4 arms (37.0% in the placebo group, 39.3% in the 100 mg group, 48.1% in the 200 mg group, and 46.3% in the 400/200 mg group). A higher ACR20 response became apparent in a dose-dependent manner in patients who expressed higher CD16+ monocytes at week 24 (30.0% for placebo, 46.7% for 100 mg, 57.7% for 200 mg, and 69.6% for 400/200 mg). E6011 also demonstrated a favourable safety profile and was generally well-tolerated during the study period.

1. Nanki T, et al. Mod Rheumatol. 2017 May;27(3):392-397.
2. Tanaka Y, et al. Abstract OP0223. EULAR 2019

Posted on 4 September 201917 March 2021