Delving into the Latest Updates on CSJ-148 with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

+ [5]

Target-

Mechanism-

Therapeutic Areas

Infectious Diseases

Active Indication-

Inactive Indication

Cytomegalovirus Infections

Originator Organization

Humabs BioMed SA

Active Organization-

Inactive Organization

Novartis Pharmaceuticals Corp.

Humabs BioMed SA

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 14200429L

Sequence Code 13793276H

Sequence Code 14013502H

Sequence Code 13924188L

Author: Ramachandra, Sangana ; Akard, Luke ; Holler, Ernst ; Maertens, Johan ; Hiemenz, John ; Mielke, Stephan ; Wang, Po-Nan ; Yeh, Su-Peng ; Yeo, Adeline ; Winkler, Julia ; Long, Gwynn ; Christoph, Sandra ; Segal, Florencia ; Koh, Liang Piu ; Lee, Dong-Gun ; Tang, Jih-Luh ; Chemaly, Roy ; Hwang, William Y. K. ; Pertel, Peter ; Gerbitz, Armin ; Jang, Junho ; Logan, Aaron C. ; Smith, Kristin

Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients, and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the functions of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. In this phase 2, randomized, placebo-controlled trial, we evaluated the safety and efficacy of CSJ148 for prophylaxis of HCMV in patients undergoing allogeneic hematopoietic stem cell transplantation.

01 Aug 2016·Antimicrobial Agents and ChemotherapyQ2 · MEDICINE

In Vitro Characterization of Human Cytomegalovirus-Targeting Therapeutic Monoclonal Antibodies LJP538 and LJP539

Q2 · MEDICINE

Article

Author: Zhong, Weidong ; Lin, James J. ; Jarousse, Nadine ; Skewes-Cox, Peter ; Nikitin, Pavel ; Ciferri, Claudio ; Barkan, David T. ; Patel, Hetalkumar D. ; Wiedmann, Brigitte ; Gesner, Thomas ; Hebner, Christy M. ; Carfi, Andrea ; Akbarnejad Yazdi, Tahmineh ; Feire, Adam

ABSTRACT Human cytomegalovirus (HCMV) infection is usually benign in healthy individuals but can cause life-threatening disease in those with compromised immune systems. Approved drugs available to treat HCMV disease, including ganciclovir, cidofovir, and foscarnet, have significant toxicities that limit their use in certain patient populations. LJP538 and LJP539 are human monoclonal antibodies that are being evaluated as immunoglobulin therapeutics. The antibodies target glycoproteins gB and the gH/gL/UL128/UL130/UL131a pentameric complex, respectively. Here we present an in vitro characterization of these antibodies. We show that LJP538 and LJP539 are more potent than a marketed immunoglobulin at inhibiting HCMV infection of various cell lines relevant to pathogenesis. We find that LJP538 and LJP539 are active against a panel of clinical isolates in vitro and demonstrate minor-to-moderate synergy in combination. Passage of HCMV in the presence of LJP538 or LJP539 alone resulted in resistance-associated mutations that mapped to the target genes. However, no loss of susceptibility to the combination of antibodies was observed for >400 days in culture. Finally, the binding regions of LJP538 and LJP539 are conserved among clinical isolates. Taken together, these data support the use of LJP538 and LJP539 in combination for clinical trials in HCMV patients.

01 May 2016·Antimicrobial Agents and ChemotherapyQ2 · MEDICINE

A First-in-Human Study To Assess the Safety and Pharmacokinetics of Monoclonal Antibodies against Human Cytomegalovirus in Healthy Volunteers

Q2 · MEDICINE

Article

Author: Pang, Yinuo ; Rondon, Juan C. ; Pertel, Peter ; Dole, Kiran ; Yu, Jing ; Feire, Adam ; Magnusson, Baldur ; Segal, Florencia Pereyra ; Vemula, Janardhana

ABSTRACTHuman cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the function of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. Here, we evaluated the safety, tolerability, and pharmacokinetics of a single intravenous dose of LJP538 or LJP539 or their combination in healthy volunteers. Adverse events and laboratory abnormalities occurred sporadically with similar incidence between antibody and placebo groups and without any apparent relationship to dose. No subject who received antibody developed a hypersensitivity, infusion-related reaction or anti-drug antibodies. After intravenous administration, both LJP538 and LJP539 demonstrated typical human IgG1 pharmacokinetic properties, with slow clearances, limited volumes of distribution, and long terminal half-lives. The pharmacokinetic parameters were linear and dose proportional for both antibodies across the 50-fold range of doses evaluated in the study. There was no apparent impact on pharmacokinetics when the antibodies were administered alone or in combination. CSJ148 and the individual monoclonal antibodies were safe and well tolerated, with pharmacokinetics as expected for human immunoglobulin.

100 Deals associated with CSJ-148

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cytomegalovirus Infections	Phase 2	-	Humabs BioMed SA	-
Cytomegalovirus Infections	Phase 2	-	Humabs BioMed SA	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02268526 (Pubmed) Manual	Phase 2	Cytomegalovirus Infections	-	CSJ148	nxwjlegmhs(wkygmhsabi): RR = 0.89 (90% CI, 0.61 - 1.31)	Negative	24 Mar 2020
				placebo
NCT02268526 (CTgov)	Phase 2	Cytomegalovirus Infections	86	CSJ148 (Cohort 2: CSJ148)	qccdnmgmdp(luzjfhymqt) = goljjwfxjh dtsvbrmdqd (qoyhypzywq, qebtwetueu - hbgijfiege) View more	-	26 Feb 2018
				Placebo (Cohort 2: Placebo)	qccdnmgmdp(luzjfhymqt) = zjqlczvpcu dtsvbrmdqd (qoyhypzywq, fmahobwuah - fdhniowmvw) View more