SAT0126 A PHASE 2 STUDY OF E6011, AN ANTI-FRACTALKINE MONOCLONAL ANTIBODY, IN PATIENTS WITH RHEUMATOID ARTHRITIS INADEQUATELY RESPONDING TO BIOLOGICS
Authors: Yoshiya Tanaka, Tsutomu Takeuchi, Hisashi Yamanaka, Toshihiro Nanki, Hisanori Umehara, Nobuyuki Yasuda, Fumitoshi Tago, Yasumi Kitahara, Makoto Kawakubo, Hayato Hisaki, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Fractalkine (CX3CL1, designated as FKN hereafter) is the sole member of the CX3C-chemokine which leads to dual actions, chemotaxis and cell adhesion for leukocytes expressing the cognate receptor, CX3CR1, during their migration. We have conducted clinical trials of E6011, a novel humanized anti-FKN monoclonal antibody, for patients with rheumatoid arthritis (RA) in Japan<sup>1</sup>. This is the first report of a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study of E6011 in RA patients inadequately responding to biologics (NCT02960490). <h3>Objectives</h3> To evaluate efficacy and safety of E6011 compared with placebo. <h3>Methods</h3> During the 24-week double-blind period, patients with moderately to severely active RA of inadequate response to biologics were randomly assigned to E6011 400 mg or placebo groups at a 1:1 ratio. Patients who continued the study beyond Week 12 were further allocated to E6011 200 mg or 400 mg at a 1:1 ratio within the initially assigned group. Patients received either E6011 400 mg or placebo at Weeks 0, 1, 2, and every 2 weeks subsequently until Week 10 and then E6011 200 mg or 400 mg every 2 weeks between Weeks 12 and 22 in a double-blind manner. This abstract reports the results from the first 12-week placebo controlled period. <h3>Results</h3> A total of 64 subjects (33 in the placebo group and 31 in the E6011 400 mg group) received study drug. Of the 64 subjects, 55 completed and 9 discontinued study treatment prematurely during the 12-week placebo controlled double-blind period. The ACR20 response rate at Week 12 (non-responder imputation), the primary endpoint, was 27.3% (9/33 subjects) in the placebo group and 22.6% (7/31 subjects) in the E6011 group. ACR50 and ACR70 response rate at Week 12 were 3.0%, 0% in the placebo group and 9.7%, 3.2% in the E6011 group, respectively. Numerically greater improvement from baseline was found for some parameters of the ACR components in the E6011 group, however, no statistically significant differences were found in any of the ACR components between the placebo and E6011 groups. From the exploratory PK exposure analysis, there was a tendency that the effect of E6011 became clearer in the subjects who achieved higher serum trough E6011 concentration. Adverse events that occurred in at least 2 subjects in the E6011 group were stomatitis, injection site erythema, nasopharyngitis, and blood creatine phosphokinase increased. As a results, E6011 was well tolerated with no notable safety concerns at doses of 400 mg when administered subcutaneously for 12 weeks. <h3>Conclusion</h3> E6011 400 mg was well tolerated but did not show clear efficacy at Week 12 compared with placebo in RA patients with inadequately responding to biologics. Further investigation to seek an optimal clinical dose and evaluation period of E6011 are warranted. <h3>Reference</h3> [1] Tanaka Y, et al., Mod Rheumatol (2018) 28, 58-65 <h3>Acknowledgement</h3> The authors wish to thank the study investigators. <h3>Disclosure of Interests</h3> Yoshiya Tanaka Grant/research support from: Abbvie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, Taisho-Toyama, Takeda, Speakers bureau: Abbvie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai, Glaxo-Smithkline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer Japan Inc, Sanofi, Takeda, UCB, YL Biologics, Tsutomu Takeuchi Grant/research support from: Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co. Ltd., Novartis Pharma K.K., Grant/research support from: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Grant/research support from: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., GlaxoSmithKline K.K., UCB Japan Co. Ltd., Consultant for: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd., Bristol Myers Squibb, and Nipponkayaku Co. Ltd., Speakers bureau: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Speakers bureau: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Astellas Pharma Inc, Diaichi Sankyo Co. Ltd., Eisai Co. Ltd., Sanofi K.K., Teijin Pharma Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharma K.K., Hisashi Yamanaka Grant/research support from: AbbVie, Eisai, Bristol-Meyers, Novartis, Behringer, Astellas, Kaken, Nippon-Shinyaku, Pfizer, UCB, Ayumi, Ono, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, YLbio, Speakers bureau: Bristol-Meyers, Astellas, Pfizer, Daiichi-Sankyo, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, YLbio, Toshihiro Nanki Grant/research support from: Chugai, Eisai, Takeda, Teijin, Eli Lilly, Bristol-Myers, AbbVie, Ono, Novartis, Asahikasei, Mitsubishi-Tanabe, Astellas, Ayumi, Pfizer, Daiichi Sankyo, Shionogi, Sanofi, Nippon Kayaku, Yutoku, Actelion, UCB, Bayer, Nihon Pharmaceutical., Consultant for: UCB, Eisai, Chugai, Ono, Gilead., Speakers bureau: Mitsubishi-Tanabe, Chugai, Eisai, Takeda, Astellas, Janssen, Eli Lilly, Ayumi, Pfizer, Asahikasei, Sanofi, Daiichi Sankyo, Otsuka, AbbVie, Ono, Teijin, Nippon Kayaku, UCB., Hisanori Umehara: None declared, Nobuyuki Yasuda Shareholder of: Eisai Co., Ltd., Employee of: KAN Research Institute, Inc. (subsidiary of Eisai Co., Ltd.), Fumitoshi Tago Employee of: Eisai Co., Ltd., Yasumi Kitahara Shareholder of: Eisai Co., Ltd., Employee of: Eisai Co., Ltd., Makoto Kawakubo Shareholder of: Eisai Co., Ltd., Employee of: Eisai Co., Ltd., Hayato Hisaki Shareholder of: Eisai Co., Ltd., Employee of: Eisai Co., Ltd., Seiichiro Hojo Employee of: Eisai Co., Ltd., Tetsu Kawano Employee of: KAN Research Institute, Inc. (subsidiary of Eisai Co., Ltd.), Toshio Imai Shareholder of: Eisai Co., Ltd., Employee of: KAN Research Institute, Inc. (subsidiary of Eisai Co., Ltd.)