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

Mechanism

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

Therapeutic Areas

Infectious Diseases

Active Indication-

Inactive Indication

Clostridium difficile infection

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Merck Sharp & Dohme LLC

Drug Highest PhasePendingPhase 3

First Approval Date-

Regulation-

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Gene 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.

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

EUCTR2011-004590-90-ES / Not yet recruitingPhase 3

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(MODIFY I) - MODIFY I

Start Date27 Jan 2012

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

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 ; Green, Kassidy ; López, Tomás ; 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 Jan 2020·Animal Science JournalQ3 · AGRICULTURAL & FORESTRY SCIENCE

Administration of L. salivarius expressing 3D8 scFv as a feed additive improved the growth performance, immune homeostasis, and gut microbiota of chickens

Q3 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Oh, Keon Bong ; Byun, Sung June ; Lee, Sukchan ; Lee, Hae Sun ; Lee, Hwi Cheul ; Sureshkumar, Shanmugam ; Yang, Hyeon ; Kim, Dongjun ; Jung, Sun Keun ; Jo, Yong Jin

AbstractProbiotics have been defined as live microorganisms that are administered in an appropriate amount to provide health benefits to the host animal. In this study, we investigated the effect of L. salivarius DJ‐sa‐01 secreting the 3D8 single‐chain variable fragment (3D8 scFv) on the growth performance, cytokine secretion, and intestinal microbial flora of chickens. The experiment was divided into the control group and L. salivarius expressing 3D8 scFv experimental group. Chicken was fed 109 colony‐forming units (CFUs) of wild‐type (WT) L. salivarius or 3D8 scFv‐secreting L. salivarius daily for 35 days. The administration of L. salivarius expressing 3D8 scFv significantly improved the body weight of chickens compared with the administration of WT L. salivarius. A 16S ribosomal RNA metagenomic analysis showed that Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were the dominant phyla in both experimental groups. At the genus level, Lactobacillus was more abundant (22.82%) in the L. salivarius/3D8 group compared with the WT L. salivarius group. The serum levels of cytokines, such as IL‐8, TNF‐α, IL‐1β, IFN‐γ, IL‐4, and IGF1, were significantly reduced in the L. salivarius/3D8‐treated chickens. In summary, our results suggest that L. salivarius expressing 3D8 scFv could be considered a feed additive for improving the growth performance, immune function, and disease resistance of poultry.

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 ; Choi, Hoonsung ; Kim, Kyung-Woon ; Kim, Jeom Sun ; Jeon, Ik-Soo ; Lee, Sukchan ; 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.

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

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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)	visehbfsiw(dipungasqs) = sxxqtnyqrd qyyrbsakro (fhffvfoguz, rpjhcwjgfg - qxnjbkjeqy) View more	-	09 Feb 2021
				normal saline (Placebo)	visehbfsiw(dipungasqs) = ohflbqqzfj qyyrbsakro (fhffvfoguz, ozhlbmxcvg - oekeslmxgc) View more
MODIFY I and MODIFY II (Pubmed \| Br Dent J)	Phase 3	Clostridium difficile infection	2,655	Bezlotoxumab	esohdqhpxl(spzcrjelzx) = okqtlayhbc ufvrcvrlyt (gzzjvhowzv ) View more	Positive	26 Jan 2017
				Actoxumab plus Bezlotoxumab	esohdqhpxl(spzcrjelzx) = ykmnjhhgnt ufvrcvrlyt (gzzjvhowzv ) View more
NCT01513239 (MODIFY II \| 3415A-002, CTgov)	Phase 3	Clostridium difficile infection	1,203	SOC+MK-3415A (MK-3415A + SOC)	booknvsimv(fwltofwjfx) = tewtpigwie rfcdyoagbc (fqrbayomgy, effyqvpzri - adosowbpzo) View more	-	15 Dec 2016
				SOC+MK-6072 (MK-6072 + SOC)	booknvsimv(fwltofwjfx) = gutevncusc rfcdyoagbc (fqrbayomgy, zabovwqfac - beusmlebxw) View more
NCT01241552 (MODIFY I \| 3415A-001, CTgov)	Phase 3	Clostridium difficile infection	1,452	SOC+MK-3415 (MK-3415 + SOC)	ilqlwjyixc(qdgczwlzea) = nzogzotzhw ehhjnixeld (dloucgkshm, rrqlguskme - xychcrlsgh) View more	-	15 Dec 2016
				SOC+MK-6072 (MK-6072 + SOC)	ilqlwjyixc(qdgczwlzea) = fqznpftmdz ehhjnixeld (dloucgkshm, zsgxpdvecs - pioafvwcex) View more