A phase 2 study of E6011, an anti-Fractalkine monoclonal antibody, in patients with rheumatoid arthritis inadequately responding to biological disease-modifying antirheumatic drugs

Abstract

Objectives

To evaluate the safety and efficacy of E6011, a novel humanized anti-fractalkine monoclonal antibody, in patients with active rheumatoid arthritis (RA) with an inadequate response to biological disease-modifying antirheumatic drugs (DMARDs).

Methods

Active RA patients inadequately responding to biological DMARDs were randomly assigned to placebo or E6011 400-mg group at a 1:1 ratio, and administered E6011 at weeks 0, 1, 2, and subsequently every 2 weeks. Primary endpoint was American College of Rheumatology (ACR)20 response at week 12.

Results

Of 64, 33 received placebo, 31 received E6011 400-mg. The ACR20 response rate at week 12 (non-responder imputation) was 27.3% and 22.6% in the placebo and E6011 groups, respectively. ACR50, ACR70 response rates at week 12 were 3.0%, 0% in the placebo and 9.7%, 3.2% in the E6011 group. Exploratory PK exposure analysis revealed that the effect of E6011 tended to be clearer in patients with higher serum trough E6011 concentration. E6011 was well tolerated with no notable safety concerns.

Conclusions

E6011 400-mg was well tolerated but had no clear efficacy at week 12 in RA patients with inadequate response to biologics. Further investigations are warranted to determine the optimal clinical dose and evaluation period for E6011.

Keywords:

• E6011
• fractalkine
• monoclonal antibody
• rheumatoid arthritis

Conflict of interest

Yoshiya Tanaka, has received speaking fees and/or honoraria from Daiichi-Sankyo Co., Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., YL Biologics Ltd., Bristol-Myers Squibb K.K., Eisai Co., Ltd., Chugai Pharmaceutical Co., AbbVie GK., Astellas Pharma Inc., (>$10,000), Pfizer Japan Inc., Sanofi K.K., Asahi-Kasei Pharma Corp., GlaxoSmithKline K.K., Mitsubishi- Tanabe Pharma Co., Gilead Sciences, Inc., Janssen Pharmaceutical K.K. (<$10,000) and has received research grants from AbbVie GK., Mitsubishi- Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Asahi-Kasei Pharma Corp., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd., Daiichi-Sankyo Co., Ltd. (>$10,000); Tsutomu Takeuchi has received consulting fees, speaking fees and/or honoraria from AbbVie GK., Asahi-Kasei Pharma Corp., Astellas Pharma Inc., Eisai Co., Ltd., JCR Pharma., Mitsubishi- Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Nippon Kayaku Co., UCB Japan., Bristol-Myers Squibb K.K. (>$10,000) and Daiichi-Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd.; Ono Pharmaceutical Co., Ltd., Gilead Sciences, Inc., Taiho Pharmaceutical Co., Ltd., Taisho Pharma Co., Ltd., A2 healthcare corporation., GlaxoSmithKline K.K., Eli Lilly Japan K.K., Boehringer Ingelheim Japan,. Novartis Pharma K.K., AYUMI Pharmaceutical Corporation, Pfizer Japan Inc., Sanofi K.K (<$10,000); Hisashi Yamanaka has received consulting fees, speaking fees, and/or honoraria from

Teijin Pharma Ltd., YL Biologics Ltd.; (>$10,000) and AbbVie GK., Astellas Pharma Inc., AYUMI Pharmaceutical Corporation, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co, Ltd., Daiichi-Sankyo Co., Ltd., Eisai Co., Ltd., Kaken Pharmaceutical Co., Ltd., Mitsubishi- Tanabe Pharma Co., Nippon Boehringer Ingelheim Co., Ltd., Nippon Shinyaku Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Taisho Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Torii Pharmaceutical Co., Ltd., UCB Japan. (<$10,000); Toshihiro Nanki has received consulting fees, speaking fees, and/or honoraria from Mitsubishi-Tanabe Pharma Co., Chugai Pharmaceutical Co., Eisai Co., Ltd., Asahi-Kasei Pharma Corp., Bristol-Myers K.K., Ono Pharmaceutical Co., Ltd., AYUMI Pharmaceutical Corporation, Bayer Yakuhin, Ltd., AbbVie GK., Eli Lilly Japan K.K., Novartis Pharma K.K., Astellas Pharma Inc., Nippon Kayaku Co., Ltd. (>$10,000), and Daiichi Sankyo Co., Ltd., Teijin Pharma Ltd., Takeda Pharmaceutical Co., Ltd., SHIONOGI & CO., LTD., UCB Japan Co., Ltd., Sanofi K.K., Nippon Boehringer Ingelheim Co., Ltd., Pfizer Japan Inc., NIHON PHARMACEUTICAL CO., LTD., Yutoku Pharmaceutical Ind. Co., Ltd., Janssen Pharmaceutical K.K., Gilead Sciences, Inc., TAIHO Pharmaceutical Co., Ltd. (<$10,000); Hisanori Umehara reports consultancy fees from Eisai Co., Ltd. (<$10,000); Nobuyuki Yasuda is employee of KAN Research Institute, Inc.; Fumitoshi Tago, Yasumi Kitahara, Makoto Kawakubo, Kentaro Torii, and Seiichiro Hojo are employees of Eisai Co., Ltd.; Tetsu Kawano and Toshio Imai are employees of KAN Research Institute, Inc.

Additional information

Funding

This work was supported by Eisai. Co., Ltd. The authors wish to thank the study participants and all investigators.