Delving into the Latest Updates on Actoxumab/Bezlotoxumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Bezlotoxumab/actoxumab

+ [8]

Target

toxA x toxB

Action

inhibitors

Mechanism

toxA inhibitors(Toxin A inhibitors), toxB inhibitors(Toxin B inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication-

Inactive Indication

Clostridium difficile colitisClostridium difficile infection

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Medarex, Inc.Merck Sharp & Dohme LLC

License Organization

UMass Chan Medical School

Merck & Co., Inc.

Medarex, Inc.

Drug Highest PhasePendingPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 9173798L

The sequence is quoted from: *****

Sequence Code 319373281H

The sequence is quoted from: *****

Sequence Code 13006926H

The sequence is quoted from: *****

Sequence Code 9173761L

The sequence is quoted from: *****

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of a Single Infusion of MK-6072 (Human Monoclonal Antibody to C. difficile toxin B), and MK-3415A (Human Monoclonal Antibodies to C. difficile toxin A and B) in Patients Receiving Antibiotic Therapy for C. difficile Infection (MODIFY II) - MODIFY II

Start Date06 Mar 2012

Sponsor / Collaborator

Merck & Co., Inc.

EUCTR2011-004590-90-AT

/ Not yet recruitingNot Applicable

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Adaptive Design Study of the Efficacy, Safety, and Tolerability of a Single Infusion of MK-3415 (Human Monoclonal Antibody to Clostridium difficile toxin A), MK-6072 (Human Monoclonal Antibody to Clostridium difficile toxin B), and MK-3415A (Human Monoclonal Antibodies to Clostridium difficile toxin A and toxin B) in Patients Receiving Antibiotic Therapy for Clostridium difficile Infection - Effectiveness of MK-3415A Given with SOC vs. Placebo

Start Date16 Feb 2012

Sponsor / Collaborator-

NCT01513239

/ CompletedPhase 3

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of a Single Infusion of MK-6072 (Human Monoclonal Antibody to Clostridium Difficile Toxin B), and MK-3415A (Human Monoclonal Antibodies to Clostridium Difficile Toxin A and B) in Patients Receiving Antibiotic Therapy for Clostridium Difficile Infection (MODIFY II)

MK-3415A is the combination of monoclonal antibodies to Clostridium (C.) difficile toxin A (MK-3415) and toxin B (MK-6072). This study will investigate whether: 1) treatment with MK-6072 or MK-3415A in addition to standard of care (SOC) antibiotic therapy will decrease Clostridium Difficile Infection (CDI) recurrence compared with placebo; and 2) MK-6072 and MK-3415A will be generally well tolerated in participants receiving SOC therapy for CDI compared with placebo.

Start Date01 Feb 2012

Sponsor / Collaborator

Merck Sharp & Dohme LLC

100 Clinical Results associated with Actoxumab/Bezlotoxumab

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100 Translational Medicine associated with Actoxumab/Bezlotoxumab

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100 Patents (Medical) associated with Actoxumab/Bezlotoxumab

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23

Literatures (Medical) associated with Actoxumab/Bezlotoxumab

23 Jul 2024·Journal of Virology

Mouse and human immune responses share neutralization epitopes of HAstV-VA1

Article

Author: Arias, Carlos F ; Alpuche-Aranda, Celia M ; DuBois, Rebecca M ; López, Susana ; Gaspar-Castillo, Carlos ; Ramírez-Bello, Inci ; Riaño-Umbarila, Lidia ; Ghosh, Anisa ; Espinosa, Rafaela ; López, Tomás ; Green, Kassidy ; Aguilera-Flores, Catalina

ABSTRACTAstroviruses are highly divergent and infect a wide variety of animal hosts. In 2009, a genetically divergent human astrovirus (HAstV) strain VA1 was first identified in an outbreak of acute gastroenteritis. This strain has also been associated with fatal central nervous system disease. In this work, we report the isolation of three high-affinity neutralizing monoclonal antibodies (Nt-MAbs) targeting the capsid spike domain of HAstV-VA1. These antibodies (7C8, 2A2, 3D8) were used to select individual HAstV-VA1 mutants resistant to their neutralizing activity and a HAstV-VA1 triple mutant that escapes neutralization from all three Nt-MAbs. Sequencing of the virus genome capsid region revealed escape mutations that map to the surface of the capsid spike domain, define three potentially independent neutralization epitopes, and help delineate four antigenic sites in human astroviruses. Notably, two of the escape mutations were found to be present in the spike sequence of the HAstV-VA1-PS strain isolated from an immunodeficient patient with encephalitis, suggesting that those mutations arose as a result of the immune pressure generated by the patient’s immunotherapy. In agreement with this observation, human serum samples exhibiting strong neutralization activity against wild-type HAstV-VA1 had a 2.6-fold reduction in neutralization titer when evaluated against the triple-escape HAstV-VA1 mutant, suggesting that both mouse and human antibody responses target shared neutralization epitopes. The isolated Nt-MAbs reported in this work will help to characterize the functional domains of the virus during cell entry and have the potential for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1.IMPORTANCEHuman astroviruses (HAstVs) have been historically associated with acute gastroenteritis. However, the genetically divergent HAstV-VA1 strain has been associated with central nervous system disease. In this work high-affinity neutralizing monoclonal antibodies directed to HAstV-VA1 were isolated and characterized. The proposed binding sites for these antibodies and for neutralizing antibodies against classical HAstVs suggest that there are at least four neutralization sites on the capsid spike of astroviruses. Our data show that natural infection with human astrovirus VA1 elicits a robust humoral immune response that targets the same antigenic sites recognized by the mouse monoclonal antibodies and strongly suggests the emergence of a variant HAstV-VA1 virus in an immunodeficient patient with prolonged astrovirus infection. The isolated Nt-MAb reported in this work will help to define the functional sites of the virus involved in cell entry and hold promise for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1.

01 Dec 2019·Acta Veterinaria HungaricaQ4 · AGRICULTURAL & FORESTRY SCIENCE

Avian influenza virus transmission is suppressed in chickens fed Lactobacillus paracasei expressing the 3D8 single-chain variable fragment protein

Q4 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Park, Mi-Ryung ; Byun, Sung June ; Kim, Jeom Sun ; Choi, Hoonsung ; Kim, Kyung-Woon ; Lee, Sukchan ; Jeon, Ik-Soo ; Lee, Sang In ; Sureshkumar, Shanmugam ; Jeon, Mi-Hyang

The 3D8 single-chain variable fragment (scFv) is a mini-antibody sequence with independent nuclease activity that shows antiviral effects against all types of viruses in chickens and mice. In this study, chickens were treated daily with an oral dose of 109 CFU Lactobacillus paracasei (L. paracasei) expressing either a secreted or anchored 3D8 scFv for three weeks. After L. paracasei administration, the chickens were challenged with avian influenza virus (AIV). From each experimental group, three chickens were directly infected with 100 µL of 107.5 EID50/mL H9N2 AIV and seven chickens were indirectly challenged through contact transmission. oropharyngeal and cloacal swab samples were collected at 3, 5, 7, and 9 days post-inoculation (dpi) from AIV-challenged chickens, AIV Shedding titres were measured by quantitative real-time PCR. Contact transmission in the chickens that were fed 3D8 scFv-secreting L. paracasei showed a significant reduction in viral shedding when compared with other groups. These results suggest that L. paracasei secreting 3D8 provides a basis for the development of ingestible antiviral probiotics with activity against AIV.

01 Dec 2018·Emerging Microbes & InfectionsQ2 · MEDICINE

Broadly neutralizing monoclonal antibodies against human adenovirus types 55, 14p, 7, and 11 generated with recombinant type 11 fiber knob

Q2 · MEDICINE

ArticleOA

Author: Fan, Ye ; Qiu, Hongling ; Tian, Xingui ; Liao, Jiayi ; Liu, Tiantian ; Liu, Wenkuan ; Zhou, Zhichao ; Liu, Zhenwei ; Li, Xiao ; Zhou, Rong ; Zhang, Ling

The re-emerging human adenovirus types HAdV7, HAdV14, and HAdV55 of species B have caused severe lower respiratory tract diseases and even deaths during recent outbreaks. However, no adenovirus vaccine or therapeutic has been approved for general use. These adenoviruses attach to host cells via the knob domain of the fiber, using human desmoglein 2 as the primary cellular receptor. In this study, a recombinant HAdV11 fiber knob trimer (HAdV11FK) expressed in E. coli was shown to induce broadly neutralizing antibodies against HAdV11, -7, -14p1, and -55 in mice. Using HAdV11FK as an antigen, three monoclonal antibodies, 6A7, 3F11, and 3D8, with high neutralizing activity were generated. More importantly, the results of in vitro neutralization assays demonstrated that 3F11 and 3D8 cross-neutralized HAdV11, -7, and -55, but not HAdV14p1. The amino acids 251KE252 within the F-G loop may be the crucial amino acids in the conformational epitope recognized by 3F11, which is common to HAdV11, -7, -14p, and -55, but is not present in HAdV14p1 and HAdV3. A two-amino-acid deletion in the HAdV14p1 structure breaks the short alpha helix (248SREKE252) that is present in the HAdV7, -11, -55, and -14p fiber knob structures. Our findings add to the knowledge of adenovirus fiber structure and antibody responses and are important for the design of adenovirus vaccines and antiviral drugs with broad activity.

100 Deals associated with Actoxumab/Bezlotoxumab

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Clostridium difficile infection	Phase 3	-	Merck Sharp & Dohme LLC	10 Oct 2011
Clostridium difficile colitis	Phase 3	Canada	Medarex, Inc.	20 Jul 2006
Clostridium difficile colitis	Phase 3	United States	Medarex, Inc.	20 Jul 2006

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00350298 (CTgov)	Phase 2	Clostridium difficile colitis	200	GS-CDA1/MDX-1388 (GS-CDA1/MDX-1388)	hnebyuaoix(foalfrgpvk) = kitscluksl uyzaxrqefc (awmnoqdyka, dncgxclkxu - akdsjapvxh) View more	-	09 Feb 2021
				normal saline (Placebo)	hnebyuaoix(foalfrgpvk) = ebucdyjwrd uyzaxrqefc (awmnoqdyka, beqpkwvvjh - ewbqfskmsl) View more
NCT01513239 (MODIFY II \| 3415A-002, CTgov)	Phase 3	Clostridium difficile infection	1,203	SOC+MK-3415A (MK-3415A + SOC)	gunculjjkm(kfwftvdqix) = ztxobwuhnm ldifawcydm (jkqxarczpq, rppoxysncd - vacmoqorrr) View more	-	15 Dec 2016
				SOC+MK-6072 (MK-6072 + SOC)	gunculjjkm(kfwftvdqix) = bvylldidsl ldifawcydm (jkqxarczpq, ksswurknff - qpunzgelff) View more
NCT01241552 (MODIFY I \| 3415A-001, CTgov)	Phase 3	Clostridium difficile infection	1,452	SOC+MK-3415 (MK-3415 + SOC)	xutcqzuikq(xpqrotgmoj) = bulolvnbgd vupaeeoffr (xnsrjclpiq, xjtnaompiy - ydxnvkusqz) View more	-	15 Dec 2016
				SOC+MK-6072 (MK-6072 + SOC)	xutcqzuikq(xpqrotgmoj) = qkzvhbmvkv vupaeeoffr (xnsrjclpiq, ykbborgsme - ksyqcuudnj) View more

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Biosimilar

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