Safety and Efficacy of E6011, an Anti-Fractalkine Monoclonal Antibody, in a First-in-Patient Phase 1/2 Study in Rheumatoid Arthritis

Yoshiya Tanaka¹, Tsutomu Takeuchi², Hisanori Umehara³, Toshihiro Nanki⁴, Hideto Akama⁵, Nobuyuki Yasuda⁵, Fumitoshi Tago⁵, Makoto Kawakubo⁵, Seiichiro Hojo⁵, Tetsu Kawano⁶ and Toshio Imai⁶, ¹The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan, ²Dept. of Internal Medicine, School of Medicine Keio University, Tokyo, Japan, ³Kyoto University Graduate School of Medicine, Kyoto, Japan, ⁴School of Medicine, Faculty of Medicine, Toho University, Tokyo, Japan, ⁵EISAI Co. Ltd., Tokyo, Japan, ⁶KAN Research Institute, Inc., Kobe, Japan

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: October 27, 2015

Keywords: Biologics, chemokines, Late-Breaking 2015, monoclonal antibodies and rheumatoid arthritis (RA)

Session Information

Date: Tuesday, November 10, 2015

Title: ACR Late-breaking Abstract Poster Presentations

Session Type: ACR Late-breaking Abstract Session

Session Time: 9:00AM-11:00AM

Background/Purpose: 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.
Accumulating evidence is telling that FKN-CX3CR1 axis plays a pivotal role in leukocyte/lymphocyte
accumulation in inflamed tissues in RA¹. We developed E6011, a novel
humanized anti-FKN monoclonal antibody, and its safety and tolerability was
assessed in a Phase 1/2, open-label, multiple ascending dose study in RA patients
for the first time (NCT02196558).

Methods: Active RA patients with inadequate response to MTX or TNF
inhibitors were received 7 consecutive doses (subcutaneous) of E6011 at week 0,
1, 2 and thereafter every 2 weeks up to week 10. A hundred and 200 mg of E6011
were chosen for the study as putatively appropriate doses for patients by the PK/PD
modeling previously obtained in the Ph1 healthy volunteer study of E6011. The primary
objective was safety and tolerability of E6011 in Japanese RA patients while the
efficacy of E6011 was also explored.

Results: Twelve subjects were enrolled in the cohort of 100 mg and subsequently
15 subjects were enrolled in the 200 mg cohort, in total, 27 subjects received
repeated subcutaneous administrations of E6011. As a result, repeated dose of E6011 was found safe and well tolerated. The incidence of AE,
treatment‑related AE and SAE was 59.3%, 29.6% and 7.4%, respectively. There
were no severe AE or deaths, and no significant differences were observed in the
incidence or severity of AE between the 100 mg and 200 mg cohorts.

Clinical outcome
was also available in the study in which response rates of ACR20, 50 and 70 at week 12
were 75.0%, 33.3%, 8.3% and 80.0%, 26.7%, 20.0% in the cohort of 100 and 200
mg, respectively. At week 12, 33.3% of subjects achieved DAS28-CRP remission in
both cohorts, 16.7% and 20.0% for SDAI remission and 8.3% and 26.7% for Boolean
remission were observed in the 100 and 200 mg cohorts, respectively.

Conclusion: E6011 was safe and well tolerated, and demonstrated a promising efficacy
in active RA patients with MTX or TNFi-IR. While further clinical studies are
required, the results obtained indicate that a novel biological DMARD targeting
FKN/CX3CR1 interaction will be clinically beneficial for active RA patients.

Reference:

1. Nanki T. Arthritis
Rheum. 2002; 46(11):2878-83.

Disclosure: Y. Tanaka, Mistubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, 2,Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, 8; T. Takeuchi, Astellas, Bristol-Myers, Chugai, Daiichi Sankyo, Mitsubishi Tanabe, Pfizer, Santen, Takeda, Teijin, AbbVie, Asahikasei, Taisho Toyama, SymBio, 2,AbbVie, Bristol-Myers, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Pfizer, Takeda, Astellas, Daiichi Sankyo, Celtrion, Nipponkayaku, 8; H. Umehara, None; T. Nanki, Chugai, Eisai, Takeda, Teijin, Eli Lilly, Bristol-Myers, AbbVie, 2,UCB, Eisai, Chugai, 5,Mitsubishi Tanabe, Chugai, Eisai, Takeda, Astellas, Janssen, Eli Lilly, 8; H. Akama, Eisai, 3,Eisai, 1; N. Yasuda, Eisai, 3,Eisai, 1; F. Tago, Eisai, 3,Eisai, 1; M. Kawakubo, Eisai, 1,Eisai, 3; S. Hojo, Eisai, 3; T. Kawano, KAN Research Institute, 3; T. Imai, Eisai, 1,KAN Research Institute, 3.

To cite this abstract in AMA style:

Tanaka Y, Takeuchi T, Umehara H, Nanki T, Akama H, Yasuda N, Tago F, Kawakubo M, Hojo S, Kawano T, Imai T. Safety and Efficacy of E6011, an Anti-Fractalkine Monoclonal Antibody, in a First-in-Patient Phase 1/2 Study in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/safety-and-efficacy-of-e6011-an-anti-fractalkine-monoclonal-antibody-in-a-first-in-patient-phase-12-study-in-rheumatoid-arthritis/. Accessed .

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