quetmolimab (E6011) / Eisai, Keio University - LARVOL DELTA

A simple LC-MS/MS assay for the quantification of E6011, a novel anti-fractalkine monoclonal antibody, in cynomolgus monkey serum - comparison with ligand binding assay. (PubMed, J Pharm Biomed Anal) - "The serum E6011 concentrations determined by the UPLC-MS/MS were comparable to those obtained by the LBA with electrochemiluminescence detection. These findings suggest that the established simple UPLC-MS/MS assay is reproducible and can serve as an alternative assay platform."

Journal • Preclinical • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CX3CL1

A Study of E6011 in Participants With Active Crohn's Disease (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: EA Pharma Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

A Study of E6011 in Participants With Active Crohn's Disease (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: EA Pharma Co., Ltd. | Trial completion date: Sep 2024 ➔ Apr 2024

Trial completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Quantification of anti-drug antibodies against E6011, an anti-fractalkine monoclonal antibody, in monkey and human serum, by an electrochemiluminescence assay. (PubMed, J Pharmacol Toxicol Methods) - "Drug tolerance of the assay in monkey and human sera was ensured up to 100 and 1000 μg/mL E6011 at the surrogate ADA levels of 1 and 4 μg/mL, respectively. The developed assay was successfully applied to ADA quantification in monkeys and humans in support of immunogenicity assessments."

Journal • Preclinical • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CX3CL1

A Study of E6011 in Participants With Active Crohn's Disease (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: EA Pharma Co., Ltd. | N=40 ➔ 25

Enrollment change • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Long-term Evaluation of E6011, an Anti-Fractalkine Monoclonal Antibody, in Patients with Rheumatoid Arthritis Inadequately Responding to Biological Disease-modifying Antirheumatic Drugs. (PubMed, Mod Rheumatol) - "E6011 was well tolerated in active RA patients who had shown an inadequate response to biologic DMARDs, but no clear benefit in the ACR20 response rates was observed. Further studies are needed to clarify the clinical benefit of E6011."

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CX3CL1

Long-term Safety and Efficacy of E6011, an Anti-fractalkine Monoclonal Antibody, in Patients with Rheumatoid Arthritis Inadequately Responding to Methotrexate. (PubMed, Mod Rheumatol) - "E6011 was safe and well-tolerated with no notable safety concerns up to 102 weeks in RA patients with an inadequate response to MTX."

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CX3CL1

A Study of E6011 in Participants With Active Crohn's Disease (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: EA Pharma Co., Ltd. | Trial completion date: Sep 2025 ➔ Sep 2024

Trial completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

A Study of E6011 in Participants With Active Crohn's Disease (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: EA Pharma Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

A Study of E6011 in Participants With Active Crohn's Disease (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: EA Pharma Co., Ltd. | Trial completion date: Apr 2025 ➔ Sep 2025 | Trial primary completion date: Mar 2022 ➔ Sep 2022

Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Contribution to development of remedies for COVID-19: focusing on Eritoran (PubMed, Nihon Yakurigaku Zasshi) - "Eritoran (E5564) is Eisai's in-house discovered and developed investigational Toll-Like Receptor 4 (TLR4) antagonist created with natural product organic synthesis technology. E6011 inhibits the tight binding of CD16-positive monocytes (a cell population that highly expresses the FKN receptor CX3CR1) to vascular endothelial cells, which are important for the local inflammatory response. This is expected to suppress the formation and exacerbation of vasculopathy in COVID-19."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Septic Shock • CX3CL1 • TLR4

A Dose Response Study of E6011 in Participants With Rheumatoid Arthritis Inadequately Responding to Methotrexate (clinicaltrials.gov) - P2; N=273; Completed; Sponsor: Eisai Co., Ltd.; N=190 ➔ 273

Clinical • Enrollment change • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Phase 1 study on the safety and efficacy of E6011, anti-fractalkine antibody, in patients with Crohn's disease. (PubMed, J Gastroenterol Hepatol) - "E6011was well-tolerated and might be effective in CD patients. These findings need to be clarified in a randomized controlled study."

Clinical • Journal • P1 data • Crohn's disease • Gastroenterology • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • CX3CL1

A Phase 2 Study of E6011, an Anti-Fractalkine Monoclonal Antibody, in Patients with Rheumatoid Arthritis Inadequately Responding to Biological Disease-modifying Antirheumatic Drugs. (PubMed, Mod Rheumatol) - "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."

Clinical • Journal • P2 data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CX3CL1

Emerging Role of Fractalkine in the Treatment of Rheumatic Diseases. (PubMed, Immunotargets Ther) - P2 | "Taken together, the preclinical and clinical results suggest that E6011 may represent a new therapeutic approach for rheumatic diseases by suppressing a major contributor to inflammation and mitigating concomitant cardiovascular and fibrotic diseases. In this review, we describe the role of the FKN-CX3CR1 axis in rheumatic diseases and the therapeutic potential of anti-FKN monoclonal antibodies to fulfill unmet clinical needs."

Journal • Review • Cardiovascular • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • CX3CL1

Efficacy and Safety of E6011, an Anti-Fractalkine Monoclonal Antibody, in Active Rheumatoid Arthritis Patients with Inadequate Response to Methotrexate: Results of a Randomized, Double-blind, Placebo-controlled Phase 2 study. (PubMed, Arthritis Rheumatol) - "This is the first evidence that E6011, a novel cell trafficking inhibitor targeting the FKN-CX CR1 interaction, is modestly effective at 24 weeks treatment in RA patients, although the primary endpoint was not met."

Clinical • Journal • P2 data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CX3CL1

Pharmacokinetics, Pharmacodynamics, and Safety of E6011, a Novel Humanized Antifractalkine (CX3CL1) Monoclonal Antibody: A Randomized, Double-Blind, Placebo-Controlled Single-Ascending-Dose Study. (PubMed, J Clin Pharmacol) - "The dose strategy for patient studies is to select regimens that will attain a minimum serum E6011 exposure of 10 μg/mL, identified as the minimum concentration needed to saturate the target-mediated elimination pathway. Model-based drug development from preclinical stage was successful in identifying dose regimens for clinical testing."

Clinical • Journal • PK/PD data • Crohn's disease • Hepatology • Immunology • Inflammatory Bowel Disease • Primary Biliary Cholangitis • Rheumatoid Arthritis

A Study of E6011 in Japanese Subjects With Rheumatoid Arthritis (clinicaltrials.gov) - P1/2; N=53; Completed; Sponsor: Eisai Co., Ltd.; N=37 ➔ 53

Clinical • Enrollment change • Immunology • Rheumatoid Arthritis • Rheumatology

[VIRTUAL] IMMUNO-PHENOTYPIC ANALYSIS OF PERIPHERAL BLOOD MONONUCLEAR CELLS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH E6011, A HUMANIZED ANTI-FRACTALKINE MONOCLONAL ANTIBODY (EULAR 2020) - P2 | "E6011 significantly decreased the proportion of CD16 + monocytes in whole monocytes. Our results indicated that the reduction of CD16 + monocytes after initial treatment might be a sensitive marker of E6011 in peripheral blood, possibly reflecting mechanism of action of E6011, since the CD16 + monocytes highly express CX3CR1."

Clinical • Immunology • Rheumatoid Arthritis • Rheumatology • CD8 • CX3CL • NCAM1

Eisai: Scientific Day (Eisai) - "Phase 1b E6011 study: Efficacy signals in Crohn's disease"; "Clinical Response & Remission at week 12: High remission rate at 10 mg/kg in Crohn's disease"

P1 data • Inflammatory Bowel Disease

A Study of E6011 in Participants With Active Crohn's Disease (clinicaltrials.gov) - P2; N=40; Recruiting; Sponsor: EA Pharma Co., Ltd.; Trial completion date: Dec 2021 ➔ Dec 2024; Trial primary completion date: Jul 2020 ➔ Jan 2022

Clinical • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Efficacy and safety of anti-fractalkine monoclonal antibody, E6011, in patients with Crohns disease who had lost response to anti-TNF agents: A multicentre, open-label, Phase 1/2 study (ECCO-IBD 2018) - P1/2; "Conclusion E6011 has been shown to be safe and well-tolerated in the patients with Crohns disease. Blocking FKN/CX3CR1 interaction could provide a potentially novel approach for therapy of Crohns disease."

Clinical • P1/2 data • Crohn's disease

A Phase 2 Study of E6011 in Subjects With Rheumatoid Arthritis Inadequately Responding to Biologics (clinicaltrials.gov) - P2; N=64; Completed; Sponsor: Eisai Co., Ltd.; Active, not recruiting ➔ Completed

Clinical • Trial completion • CRP

A Dose Response Study of E6011 in Subjects With Rheumatoid Arthritis Inadequately Responding to Methotrexate (clinicaltrials.gov) - P2; N=190; Completed; Sponsor: Eisai Co., Ltd.; Active, not recruiting ➔ Completed

Clinical • Trial completion • CRP

Efficacy and Safety of E6011, an Anti-Fractalkine Monoclonal Antibody, in MTX-IR Patients with Rheumatoid Arthritis (ACR-ARHP 2019) - P2; "E6011 provided clinical improvements with a good safety profile in RA patients with inadequately responding to MTX. Especially, a higher efficacy of E6011 was suggested in patients with higher baseline CD16+ monocytes (%). This is the world-first evidence suggesting that a novel approach to target FKN/CX3CR1 interaction could be beneficial for RA."

Clinical