Delving into the Latest Updates on Pegacaristim with Synapse

Overview

Basic Info

Drug Type

Colony-stimulating factors

Synonyms

MGDF, Megakaryocyte growth and development factor, PEG thrombopoietin

+ [10]

Target

TPO receptor

Action

agonists

Mechanism

TPO receptor agonists(Thrombopoietin receptor agonists)

Therapeutic Areas

Hemic and Lymphatic DiseasesOther Diseases

Active Indication-

Inactive Indication

Chemotherapy-induced damageThrombocytopenia

Originator Organization

Kirin

Active Organization-

Inactive Organization

Amgen, Inc.

Kirin Holdings Co., Ltd.

ZymoGenetics, Inc.

License Organization-

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 444637

Source: *****

The two generations of thrombopoietin (TPO) receptor (R) agonists have had utility in a number of hematologic conditions. However their use has often been surprisingly complex and drawbacks have been revealed in certain conditions more than in others. The first-generation megakaryocyte growth and development factor (MGDF) was discontinued due to the production of antibodies against it that cross-reacted with native TPO. Nonetheless it was tested in a wide variety of thrombocytopenic conditions and showed unequivocal efficacy in increasing the number of platelets in certain ones. As a result of lessons learned with MGDF, second-generation TPO-R agonists romiplostim and eltrombopag were initially tested and have been approved for the treatment of chronic immune thrombocytopenia (ITP), thrombocytopenia in hepatitis C, and recently aplastic anemia. These agents have had more mixed outcomes in diseases such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Results of several studies will be discussed.

01 Nov 2012·Cell TransplantationQ3 · MEDICINE

Definitive Setup of Clinical Scale Procedure for Ex Vivo Expansion of Cord Blood Hematopoietic Cells for Transplantation

Q3 · MEDICINE

ArticleOA

Author: Ivanovic, Zoran ; Chevaleyre, Jean ; Vlaski, Marija ; Milpied, Noel ; Dazey, Bernard ; Boiron, Jean-Michel ; Duchez, Pascale

We recently developed a clinical grade ex vivo cord blood expansion procedure enabling a massive amplification of hematopoietic progenitors without any loss of stem cell potential. This procedure, based on day 14 liquid cultures of cord blood CD34+cells, in medium Macopharma HP01 and in the presence of stem cell factor (SCF; 100 ng/ml), fms-related tyrosine kinase 3-ligand (Flt-3L; 100 ng/ml), megakaryocyte growth and developmental factor (MGDF; 100 ng/ml), and granulocyte colony-stimulating factor (G-CSF; 10 ng/ml) had to be modified due to the commercially unavailability of clinical grade MGDF molecule. So MGDF was replaced by thrombopoietin (TPO) in fivefold lower dose (20 ng/ml), and culture time was reduced to 12 days. That way, a mean expansion fold of 400, 80, and 150 was obtained for total cells, CD34+cells, and colony-forming cells (CFCs), respectively. This amplification was associated with a slight enhancing effect on stem cells [Scid repopulating cells (SRCs)]. These are the ultimate preclinical modifications of a clinical grade expansion protocol, which is already employed in an ongoing clinical trial.

01 Feb 2011·Journal of Gastroenterology and HepatologyQ3 · MEDICINE

Platelets prevent acute hepatitis induced by anti‐fas antibody

Q3 · MEDICINE

Article

Author: Nobuhiro Ohkohchi ; Keisuke Kohno ; Soichiro Murata ; Osamu Ikeda ; Motonobu Watanabe ; Kazuhiro Takahashi ; Ryota Matsuo ; Katsuji Hisakura ; Yoritaka Nakano ; Takuya Kawasaki ; Andriy Myronovych ; Naoya Ikeda ; Sugiru Pak

AbstractBackground and Aim: Platelets provide many functions in the body, especially to the liver. The purpose of this study is to investigate the effect of thrombocytosis with acute hepatitis induced by anti‐Fas antibody and its mechanism.Methods: Acute hepatitis was induced by administration of anti‐Fas antibody in normal and thrombocytotic C57BL6J mice. For thrombocytosis, thrombopoietin; PEG‐rHuMGDF was injected 5 days before and just prior to administration of anti‐Fas antibody. To investigate the mechanisms, hepatocyte cell line (AML12) and sinusoidal endothelial cell line (M1) were induced apoptosis by staurosporine. They were cultured with platelets or thrombopoietin. Examination items were as follows: platelet number, alanine aminotransferase (ALT), histological findings, TUNEL (TdT‐mediated dUTP‐biotin Nick End Labeling) staining, and the expression of proteins associated with apoptosis in vivo and in vitro.Results: Platelets were significantly increased in the thrombocytotic group (P < 0.01). Serum ALT levels were significantly reduced by thrombocytosis at 6, 24 and 72 h after the administration (P < 0.05). In histological findings, hemorrhagic necrosis was observed in the normal group, but not observed in the thrombocytotic group. TUNEL‐positive hepatocytes were reduced and the expression of cleaved caspase‐3 was significantly decreased in the thrombocytotic group. The phosphorylation of Akt, the increment of Bcl‐xL and the decrease of cleaved caspase‐3 were observed in AML12 cells cultured with platelets, but were not observed cultured with thrombopoietin. Platelets and thrombopoietin had no anti‐apoptotic effect on M1 cells.Conclusion: Increase of platelets has a preventative effect against acute hepatitis induced by the anti‐Fas antibody. It is suggested that platelets have a direct protective effect against apoptosis of hepatocytes.

100 Deals associated with Pegacaristim

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External Link

KEGG	Wiki	ATC	Drug Bank
D05383	-	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chemotherapy-induced damage	Phase 3	United States	ZymoGenetics, Inc.	-
Chemotherapy-induced damage	Phase 3	United States	Amgen, Inc.	-
Thrombocytopenia	Phase 3	United States	Amgen, Inc.	-
Thrombocytopenia	Phase 3	United States	ZymoGenetics, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASGCT2024	Not Applicable	T Cell Immunodeficiency Primary	-	Ligand-Conjugated Poly (Beta-Amino Ester) Nanoparticles (Poly(beta-amino ester) nanoparticles with aCD3 and aCD28 targeting ligands)	iyiqbzixln(cfiksffmbx) = particles with multiple targeting ligands (aCD3 and aCD28) achieved significantly higher T cell transfection than particles with only one or no targeting ligands hzoqqquzbq (fnlgcxlxup ) View more	-	07 May 2024
				Ligand-Conjugated Poly (Beta-Amino Ester) Nanoparticles (Poly(beta-amino ester) nanoparticles with aCD3 targeting ligand)
ARVO2023	Not Applicable	-	-	Methacrylated poly-epsilon-lysine hydrogels	(ezbjbwgpew) = rlztjeakpl dgztlwgtdh (tagwemlcrv ) View more	-	23 Apr 2023
ARVO2018	Not Applicable	Eye Injuries, Penetrating	-	functionalized poly (N-isopropylacrylamide) (PNIPAM) polymers (X13002-601 15:1)	(mwkpmcjaqg) = polymer uptake was observed at room temperature suggesting temperature dependent binding and uptake mechanism rzzpwqlmgw (mlrgoulktf )	-	01 Jul 2018
				functionalized poly (N-isopropylacrylamide) (PNIPAM) polymers (X13002-401 25:1)
APAO2018	Not Applicable	stress oxidative	-	Curcumin Poly(lactide-co-glycolide) Nanoparticles (CUR-NP)	vzmucnnphl(uyzaymqvoe) = The protective effect of CUR-NP on oxidatively stressed hTM cells may be related to mitochondrial reactive oxygen species scavenge, suppressed inflammatory gene expression, including IL-1α, IL-6, and IL-8, and reduced caspase 3 activation sdobhakbko (gyetndsgnm ) View more	-	08 Feb 2018
ASGCT2017	Not Applicable	Hepatocellular Carcinoma	-	PBAE-NP formulation	bzbunlteey(vodasfopkv) = fjwxgiihao lvkuzqdxef (ctkpbpkhxv ) View more	-	01 May 2017
				Poly(Beta-Amino Ester) (Hepatocyte line)	bperborcij(zjcgqwppzj) = iaibjwdona rmytyivavt (raaevffgco ) View more
ARVO2014	Not Applicable	hCSSCs	-	Poly(lactide-co-glycolide) (PLGA) (PLGA (100/0) scaffold)	dwynljntsh(ccurybnxsi) = collagenous ECM deposited by hCSSCs on the PLGA (50/50) substrate was much more abundant than that on PLGA (100/0) ktrenfwmyq (ehkoiiuuzv ) View more	-	01 Apr 2014
				Poly(lactide-co-glycolide) (PLGA) (PLGA (50/50) scaffold)
ARVO2012	Not Applicable	-	-	hRPE cells cultured with Rho kinase inhibitor	dcsfkzclgb(phuuoxdkel) = gkzmoedjbs uwckzygtfs (zvvzrezmqn ) View more	-	01 Mar 2012
				Poly-L-Lysine-coated plates without Rho kinase inhibitor	dcsfkzclgb(phuuoxdkel) = jaotskhcfa uwckzygtfs (zvvzrezmqn ) View more
ARVO2010	Not Applicable	-	-	EOBO alone	giwfmwkhzi(fsyiwjgxxu) = alcfwjcwcq ketahyeasa (kzsxzcwpwz ) View more	-	01 Apr 2010
				Di-Block Copolymer, Poly(oxyethylene)-Poly(oxybutylene)lysozymelymer, Poly(oxyethylene)-Poly(oxybutylene) (EOBO-lysozyme mixture)	giwfmwkhzi(fsyiwjgxxu) = cburyhnrvj ketahyeasa (kzsxzcwpwz ) View more
ARVO2008	Not Applicable	-	-	Poly(vinylpyrrolidone) hydrogel	tpvnvzzpnh(apedrzdccp) = bstrgedjxf ocfogqfgft (ynsuacdcfm ) View more	-	01 May 2008
ASGCT2007	Not Applicable	-	-	Poly(Ethylenimine) (Core polyplexes)	mueiqldtab(clpfoidjbo) = oqdbarcbop vbvjdakffb (fikxpjfkgr )	-	01 May 2007
				Poly(Ethylenimine) (Ternary polyplexes)	mueiqldtab(clpfoidjbo) = xkfqodpxvt vbvjdakffb (fikxpjfkgr )

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