Delving into the Latest Updates on Antithrombin Gamma (Genetical Recombination) with Synapse

Overview

Basic Info

Drug Type

Enzyme

Synonyms

Acoalan, Afucosylated antithrombin, Antithrombin (human variant kw-3357)

+ [6]

Target

prothrombin

Action

inhibitors

Mechanism

prothrombin inhibitors(Prothrombin inhibitors)

Therapeutic Areas

Congenital DisordersHemic and Lymphatic DiseasesCardiovascular Diseases+ [2]

Active Indication

Antithrombin III DeficiencyDisseminated Intravascular CoagulationPre-Eclampsia

Inactive Indication

Infectious Diseases

Originator Organization

Kyowa Kirin Co., Ltd.

Active Organization

Kyowa Kirin Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

Japan (03 Jul 2015),

Antithrombin III DeficiencyDisseminated Intravascular Coagulation

Regulation-

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Structure/Sequence

Sequence Code 35132

Source: *****

There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.

01 Aug 2021·Contemporary Clinical TrialsQ4 · MEDICINE

A randomized phase 3 trial evaluating antithrombin gamma treatment in Japanese patients with early-onset severe preeclampsia (KOUNO-TORI study): Study protocol

Q4 · MEDICINE

Article

Author: Kobayashi, Takao ; Sameshima, Hiroshi ; Ohkuchi, Akihide ; Takeda, Satoru ; Kanayama, Naohiro ; Takagi, Kenichi ; Sago, Haruhiko ; Seki, Hiroyuki ; Saito, Shigeru ; Masuyama, Hisashi ; Morikawa, Mamoru ; Adachi, Tomoko ; Moriya, Junji

INTRODUCTIONPreeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Several studies have demonstrated the beneficial effects of antithrombin replacement in patients with preeclampsia. Here, we describe the study protocol of KOUNO-TORI (KW-3357 randOmized, mUlti-center, double-bliNd, placebO-controlled phase 3 sTudy in patients with early Onset pReeclampsIa) to evaluate recombinant human antithrombin gamma (rhAT-gamma) for the treatment of early-onset severe de novo preeclampsia.MATERIAL AND METHODSPatients with early-onset severe de novo preeclampsia who are ≥24 to <32 weeks pregnant at the time of registration and have an antithrombin activity of ≤100% at screening are included. The target population is selected based on a reanalysis of the data of a previous plasma-derived antithrombin phase 3 study. Primary endpoint is the prolongation of pregnancy from the initiation of rhAT-gamma treatment to the pregnancy termination. Secondary endpoints include gestational age in terms of achievement of 32- and 34-weeks'gestation, and gestational age in terms of achievement of 28 weeks' gestation for patients enrolled at <28 weeks' gestation. Maternal, fetal, and neonatal outcomes will be assessed.DISCUSSIONAs we have selected a specifically defined target population based on reanalysis of data of a previous plasma-derived antithrombin phase 3 study, the results of our study are expected to provide efficacy and safety data concerning rhAT-gamma treatment in Japanese patients. This study could help identify an effective novel treatment for such patients with early-onset severe preeclampsia for whom appropriate treatment is unavailable.

01 Feb 2020·International Journal of Gynecology & ObstetricsQ4 · MEDICINE

Thromboprophylaxis with antithrombin gamma and unfractionated heparin for a pregnant woman complicated by hereditary antithrombin deficiency

Q4 · MEDICINE

Article

Author: Hisano, Michi ; Mitsui, Mari ; Sago, Haruhiko ; Yamaguchi, Koushi

Antithrombin replacement using recombinant human antithrombin (antithrombin gamma) is a well‐tolerated treatment and effective as thromboprophylaxis for a pregnant woman with hereditary antithrombin deficiency.

100 Deals associated with Antithrombin Gamma (Genetical Recombination)

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	B01AB02	DB16094

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Antithrombin III Deficiency	Japan	Kyowa Kirin Co., Ltd.	03 Jul 2015
Disseminated Intravascular Coagulation	Japan	Kyowa Kirin Co., Ltd.	03 Jul 2015

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pre-Eclampsia	Phase 3	Japan	Kyowa Kirin Co., Ltd.	19 Nov 2019
Infectious Diseases	Discovery	Japan	Kyowa Kirin Co., Ltd.	01 Jun 2011
Antithrombin III Deficiency	Discovery	United Kingdom	Kyowa Kirin Co., Ltd.	01 Apr 2009
Antithrombin III Deficiency	Discovery	Sweden	Kyowa Kirin Co., Ltd.	01 Apr 2009
Antithrombin III Deficiency	Discovery	Germany	Kyowa Kirin Co., Ltd.	01 Apr 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ISTH2019	Not Applicable	-	-	Antithrombin	almkbxmvua(uhjmqcrnqf) = iqwrperqqz xddiuhyunb (wledxetzjy )	-	10 Jun 2019
				Antithrombin	almkbxmvua(uhjmqcrnqf) = lpzprcmsem xddiuhyunb (wledxetzjy )
NCT01384903 (Pubmed \| J Intensive Care) Manual	Phase 3	Disseminated Intravascular Coagulation	222	antithrombin gamma	gbgzrmiehv(afccpfujcg) = jecxtsvbox llpnykmrfd (qonlfqebof, 46.6 - 65.8) View more	Positive	16 Nov 2018
				antithrombin	gbgzrmiehv(afccpfujcg) = kaaruwumhn llpnykmrfd (qonlfqebof, 43.0 - 62.2) View more

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Approval

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

Regulation

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Antithrombin Gamma (Genetical Recombination)

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation