Delving into the Latest Updates on Quetmolimab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Quetmolimab (USAN)

+ [2]

Target

CX3CL1

Mechanism

CX3CL1 antagonists(C-X3-C motif chemokine ligand 1 antagonists)

Therapeutic Areas

Digestive System Disorders

Active Indication

Crohn Disease

Inactive Indication

Primary Biliary CholangitisRheumatoid Arthritis

Originator Organization

Eisai Co., Ltd.

Active Organization

EA Pharma Co., Ltd.

Inactive Organization

Eisai Co., Ltd.

Eisai, Inc.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 263360826L

Source: *****

Sequence Code 263360825H

Source: *****

E6011 is a monoclonal antibody that is currently under development for the treatment of rheumatoid arthritis. While ligand binding assays (LBAs) are typically employed for the determination of therapeutic antibodies, ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) represents an alternative platform. E6011 in monkey serum was treated with ammonium sulfate to obtain pellets for subsequent processing. The pellets were subjected to denaturalization reduction, alkylation, and tryptic digestion. The resulting signature peptide of E6011, TLADGVPSR, was assayed. The pellet digestion assay was validated in accordance with the established bioanalytical guidelines. E6011 in monkey serum was quantifiable from 3 to 729 µg/mL, with a sample volume of 0.02 mL. The selectivity was confirmed in 12 individual monkey sera. The accuracy and precision were within ± 11.2 % and 15.0 %, respectively. The validated UPLC-MS/MS assay was employed in a pharmacokinetic study in monkeys. After the intravenous dose at 1 mg/kg, E6011 reached the maximum of 27.4 μg/mL, then declined with the half-life of 169 h. 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.

22 Dec 2023·Modern Rheumatology

Long-term safety and efficacy of E6011, an anti-fractalkine monoclonal antibody, in patients with rheumatoid arthritis inadequately responding to methotrexate

Article

Author: Umehara, Hisanori ; Yasuda, Nobuyuki ; Kitahara, Yasumi ; Torii, Kentaro ; Hojo, Seiichiro ; Nanki, Toshihiro ; Tanaka, Yoshiya ; Kawakubo, Makoto ; Kawano, Tetsu ; Yamanaka, Hisashi ; Takeuchi, Tsutomu ; Imai, Toshio ; Tago, Fumitoshi

ABSTRACTObjectivesTo evaluate the long-term safety and efficacy of E6011, a humanized anti-fractalkine monoclonal antibody, in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX).MethodsActive RA patients with an inadequate response to MTX were randomly assigned to the E6011 or placebo group and received the study drug subcutaneously every 2 weeks during a 24-week double-blind study period. Subjects who completed evaluations at Week 24 were rolled over into the extension phase and received open-label E6011 (200 or 400 mg) every 2 weeks until Week 102. The safety analysis was conducted up to Week 104, and the efficacy analysis was conducted up to Week 84.ResultsA total of 169 subjects completed the double-blind treatment phase and were rolled over into the extension phase. In total, 167 (98.8%) subjects experienced any adverse events, and the incidence of treatment-related adverse events was 56.2%. The American College of Rheumatology 20 response rates were observed between 40 and 70% during the extension phase.ConclusionsE6011 was safe and well tolerated with no notable safety concerns up to 102 weeks in RA patients with an inadequate response to MTX.

22 Dec 2023·Modern Rheumatology

Long-term evaluation of E6011, an anti-fractalkine monoclonal antibody, in patients with rheumatoid arthritis inadequately responding to biological disease-modifying antirheumatic drugs

Article

Author: Umehara, Hisanori ; Yasuda, Nobuyuki ; Kitahara, Yasumi ; Kawakubo, Makoto ; Nanki, Toshihiro ; Tanaka, Yoshiya ; Hojo, Seiichiro ; Torii, Kentaro ; Yamanaka, Hisashi ; Kawano, Tetsu ; Takeuchi, Tsutomu ; Imai, Toshio ; Tago, Fumitoshi

ABSTRACTObjectivesThe objective of the study is to evaluate the long-term safety and efficacy of E6011, a humanized anti-fractalkine monoclonal antibody, in patients with rheumatoid arthritis with an inadequate response to biological disease-modifying antirheumatic drugs.MethodsIn the double-blind treatment phase (24 weeks), placebo or E6011 400 mg was administered until Week 10. Thereafter, E6011 200 mg or 400 mg was administered to Week 22. Subjects who completed the evaluation at Week 24 of the treatment phase were rolled over into the extension phase. The extension phase lasted until Week 104, and all subjects received E6011 400 mg or 200 mg every 2 weeks in an open-label manner until Week 102.ResultsA total of 47 subjects completed the double-blind treatment phase and were rolled over into the extension phase. In total, 46 (97.9%) subjects experienced any adverse events, and the incidence of treatment-related adverse events was 57.4%. No clear efficacy trend in the American College of Rheumatology 20% response rates was observed.ConclusionsE6011 was well tolerated in active rheumatoid arthritis patients who had shown an inadequate response to biologic disease-modifying antirheumatic drugs, but no clear benefit in the American College of Rheumatology 20% response rates was observed. Further studies are needed to clarify the clinical benefit of E6011.

100 Deals associated with Quetmolimab

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External Link

KEGG	Wiki	ATC	Drug Bank
D11498	-	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Crohn Disease	Phase 2	RU	EA Pharma Co., Ltd.	25 Apr 2019
Crohn Disease	Phase 2	CZ	EA Pharma Co., Ltd.	25 Apr 2019
Crohn Disease	Phase 2	PL	EA Pharma Co., Ltd.	25 Apr 2019
Crohn Disease	Phase 2	HU	EA Pharma Co., Ltd.	25 Apr 2019
Crohn Disease	Phase 2	JP	EA Pharma Co., Ltd.	25 Apr 2019
Primary Biliary Cholangitis	Discovery	JP	EA Pharma Co., Ltd.	29 May 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02039063 (CTgov)	Phase 1/2	Crohn Disease	28	E6011 (Cohort 1: E6011 2 mg/kg)	(tfcrirgydn) = wvdzzmssyn yhxpmrejpj (dqvdwwbknj, rjrwbajtsq - gbqofktjqd) View more	-	30 Jan 2023
				E6011 (Cohort 2: E6011 5 mg/kg)	(tfcrirgydn) = ujzdsnlbrl yhxpmrejpj (dqvdwwbknj, irgnsovuve - aotxfgyvix) View more
NCT02960490 (CTgov)	Phase 2	Rheumatoid Arthritis	66	placebo+E6011 (Core Treatment Phase: Placebo)	lztfzqpknq(ztdmbtnywf) = omxgdawuot menbkuxkoj (qzgmbjpvdl, ybwnvavfin - bckdsmajop) View more	-	23 Aug 2021
				E6011 (Core Treatment Phase: E6011 400 mg)	lztfzqpknq(ztdmbtnywf) = thunsazphl menbkuxkoj (qzgmbjpvdl, ogigxbymwf - zwqnpqltms) View more
NCT02039063 (Pubmed \| J Gastroenterol Hepatol) Manual	Phase 1	Crohn Disease	28	E6011	(qszsbrtdcq) = qejqyoxxhc jiikbpaqkc (hnwejbtjfm ) View more	Positive	01 Aug 2021
NCT02960490 (Pubmed \| Isr Med Assoc J) Manual	Phase 2	Rheumatoid Arthritis	64	E6011	(yeifcqbwbp) = pncjrapnhx bieemhrfrt (zakkmgdavr ) View more	Negative	01 Jul 2021
				Placebo	(yeifcqbwbp) = jaqowcfxjw bieemhrfrt (zakkmgdavr ) View more
NCT02196558 (E6011, CTgov)	Phase 1/2	Rheumatoid Arthritis	53	E6011 (E6011: 100 mg)	(jgssrcjnat) = rcfbuvruch kfnclsrbxj (mbisqtovbc, lsnswsgkvt - qcavrgccxn) View more	-	13 Aug 2020
				E6011 (E6011: 200 mg)	(jgssrcjnat) = jezadmpjoa kfnclsrbxj (mbisqtovbc, yrxulnehpc - wbkattwkpp) View more
NCT02960438 (phase 2, EULAR2020)	Phase 2	Rheumatoid Arthritis CX3CR1 + \| CD16 - \| CD56 + ... View more	190	E6011	(ldcpillccr) = zyyszqbjwv mkghnajrcr (wnxmcswfiw )	Positive	03 Jun 2020
				Placebo	(ldcpillccr) = vvaswjxjwj mkghnajrcr (wnxmcswfiw )
NCT02960438 (EULAR2019)	Phase 2	Rheumatoid Arthritis CD16+ monocytes	190	E6011 100 mg	(pcjosjfhhx) = fuavyoooia fwbzwqivvp (putlnigtka )	Positive	12 Jun 2019
				E6011 200 mg	(pcjosjfhhx) = nidhvwzsct fwbzwqivvp (putlnigtka )
NCT02196558 (EULAR2017)	Phase 1/2	Rheumatoid Arthritis	37	E6011 100 mg	(jwcpbltcil) = The incidence of adverse event (AE), treatment-related AE and serious AE were 56.8%, 29.7% and 5.4%, respectively. AEs occurring in ≥2 subjects were nasopharyngitis, Injection site erythema, headache and oropharyngeal pain, among which there were no severe AEs, serious infections and deaths. No significant differences were observed in the incidence or severity of AEs across the cohorts. fnlyahwnzu (oxxngpnxbq )	-	14 Jun 2017
				E6011 200 mg
NCT02196558 (E6011, EULAR2016)	Phase 1/2	Rheumatoid Arthritis CX3CR1	27	E6011 100 mg	(yeryklzcgz) = ywobazqifs pwzrptddzy (tyiardglal ) View more	Positive	08 Jun 2016
				E6011 200 mg	(yeryklzcgz) = zhyozfzmim pwzrptddzy (tyiardglal ) View more