Delving into the Latest Updates on Lusutrombopag with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Lusutrombopag (JAN/USAN/INN)

+ [4]

Target

TPO receptor

Action

agonists

Mechanism

TPO receptor agonists(Thrombopoietin receptor agonists)

Therapeutic Areas

Hemic and Lymphatic Diseases

Active Indication

Thrombocytopenia

Inactive Indication

Chronic liver diseaseChronic thrombocytopeniaPurpura, Thrombocytopenic, Idiopathic

Originator Organization

Shionogi & Co., Ltd.

Active Organization

Shionogi, Inc.Qualicaps Netherlands BV

Suzhou SIKRO Pharmaceutical Co., Ltd

+ [2]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

Japan (28 Sep 2015),

Thrombocytopenia

RegulationFast Track (United States), Priority Review (United States)

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Structure/Sequence

Molecular FormulaC29H32Cl2N2O5S

InChIKeyNOZIJMHMKORZBA-KJCUYJGMSA-N

CAS Registry1110766-97-6

ABSTRACTBackgroundOral thrombopoietin receptor agonists are used to treat thrombocytopenia in patients with chronic liver disease who are scheduled for invasive procedures. The efficacy of lusutrombopag based on the pretreatment platelet count was investigated.MethodsPatients treated at nine hospitals from December 2015 to December 2023 were included. Efficacy was assessed by comparing the proportion of patients achieving a platelet count ≥ 50 000/μL and the change in platelet count.ResultsSeventy patients were eligible for evaluation. Patients with a pretreatment platelet count < 40 000/μL had a significantly lower rate of achieving a platelet count of ≥ 50 000/μL than those with a pretreatment count of 40 000–50 000/μL (62.5% vs. 84.2%, p = 0.038); however, there was no significant difference in the change in platelet count (25 700 vs. 24 400/μL, p = 0.972). Patients with viral‐related cirrhosis showed a significantly greater change in platelet count than the others (29 100 vs. 19 200/μL, p = 0.012). For patients receiving multiple lusutrombopag treatments, the change in platelet count was significantly lower in the second treatment than in the first treatment (26 900 vs. 20 800/μL, p = 0.041). The main adverse event observed was thrombosis (2.9%).DiscussionLusutrombopag increases platelet count regardless of pretreatment levels, but efficacy, defined as achieving a platelet count of ≥ 50 000/μL, may be insufficient in patients with a pretreatment platelet count < 40 000/μL. Additionally, patients with non‐viral liver disease responded less well to treatment compared to those with viral liver disease. Therefore, treatment strategies should be tailored based on pretreatment platelet counts and the etiology of liver disease.

20 Oct 2024·Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology

[Clinical research progress of lusutrombopag for the treatment of thrombocytopenia in chronic liver disease].

Review

Author: Wang, F S ; Xu, Z ; Zhang, J Y

Thrombocytopenia is one of the common complications with the hematologic system in patients with chronic liver disease, which often causes poor quality of life and high risk of bleeding, thereby affecting their diagnosis, treatment, and prognosis. Platelet transfusion can improve the patient's declining platelet count to a certain extent, but it has problems such as high price and being easy to cause immune rejection. Thrombopoietin (TPO), as an important cytokine that affects platelet production, can bind to TPO receptors and activate megakaryocytes to produce platelets. Lusutrombopag is a newly developed small-molecule TPO receptor agonist that can induce bone marrow progenitor cells to differentiate into megakaryocytes and increase platelet production, posing characteristics of oral convenience, safety and effectiveness; thus, it has been used in many countries and regions for the treatment of patients with chronic liver diseases concurrent with thrombocytopenia. Herein, the pharmacological features and clinical research are reviewed.

06 Sep 2024·The Journal of Organic Chemistry

Asymmetric Transfer Hydrogenation of Ketones Improved by PNN–Manganese Complexes

Article

Author: Yan, Xiuli ; Wang, Zheng ; Ma, Zhifeng ; Solan, Gregory A. ; Wang, Jingyao ; Liu, Qingbin ; Su, Yi ; Ma, Ning ; Li, Libin

Chiral manganese(I) complexes that contain carbocyclic-fused 8-amino-5,6,7,8-tetrahydroquinolinyl groups that are appended with distinct para-R substituents have proven to be effective catalysts in the asymmetric transfer hydrogenation (ATH) of a wide range of ketones (48 examples). Notably, Mn2 proved to be the most productive catalyst, allowing an outstanding turnover number of 8300 with catalyst loadings as low as 0.01 mol %. Furthermore, this catalytic protocol shows considerable promise for applications in the synthesis of chiral drugs such as Lusutrombopag.

100 Deals associated with Lusutrombopag

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External Link

KEGG	Wiki	ATC	Drug Bank
D10476	Lusutrombopag	B02BX07	DB13125

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Thrombocytopenia	Japan	Shionogi & Co., Ltd.	28 Sep 2015

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic liver disease	Discovery	-	Shionogi, Inc.	15 Jun 2015
Thrombocytopenia	Discovery	-	Shionogi, Inc.	15 Jun 2015
Chronic thrombocytopenia	Discovery	United States	Shionogi, Inc.	29 Apr 2010
Purpura, Thrombocytopenic, Idiopathic	Discovery	United States	Shionogi, Inc.	18 Mar 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CTR20192384 (Pubmed) Manual	Phase 3	Thrombocytopenia \| Chronic liver disease	66	Lusutrombopag	cuarypgcqj(xywlyrgaqw) = bubrczelfl rchmxkucak (pfuzkgkpzx ) View more	Positive	18 Oct 2022
				Placebo	cuarypgcqj(xywlyrgaqw) = bgkpekriqj rchmxkucak (pfuzkgkpzx ) View more
NCT02389621 (L-PLUS 2, Pubmed)	Phase 3	Thrombocytopenia \| Chronic liver disease	215	Lusutrombopag 3mg	pkljueywaw(oadptsmvjr) = One patient from the phase 1/2 study had a non-serious portal vein thrombosis, which was not considered treatment-related ekmtfoqgxi (whybtnexcy ) View more	-	29 Jul 2022
NCT01129024 (CTgov)	Phase 2	Purpura, Thrombocytopenic, Idiopathic \| Chronic thrombocytopenia	19	Lusutrombopag	fsusfolmdf(nvbfqsuljk) = oauojwaaxa esodbzdnsh (rzaosciszv, pwnrqwbwlo - rrogvjdtzi) View more	-	26 Feb 2021
NCT01054443 (CTgov)	Phase 2	Purpura, Thrombocytopenic, Idiopathic	20	Placebo (Placebo)	lclrxzridz(egqefeowih) = hrkszzwegm rvydlarsmo (yphhwqaplt, hbzvtvsyin - tlwxbejnqq) View more	-	24 Feb 2021
				Lusutrombopag (Lusutrombopag 0.5 mg)	lclrxzridz(egqefeowih) = ckryxcajvw rvydlarsmo (yphhwqaplt, zyrhlsymet - btdzzymaqq) View more
ISTH2019	Phase 1	Chronic liver disease	8	Lusutrombopag 3 mg	(mvsxzehyec) = lbrnmsgwvp jvzyutcxxj (ypizrbfkof )	-	10 Jun 2019
EASL2019	Not Applicable	Thrombocytopenia \| Chronic liver disease	-	Lusutrombopag 3 mg	npavjqipmv(gdhgyxpzcd) = Lower BE rates, regardless of severity and timing of onset, were observed for LUSU alone vs PBO+PT. Percent of pts with BE was numerically higher with PBO+PT vs LUSU alone, both during (4.8% vs 3.2%) and post-procedure (7.1% vs 4.0%). Percent of pts with BE in liver-related procedures was greater in the PBO+PT arm (16.1%) vs LUSU alone (11.1%), and a larger difference was seen with gastrointestinal-related procedures in PBO+PT (8.9%) vs LUSU alone (2.0%) jjmbdwdzuz (naylynsiil )	-	13 Apr 2019
				Placebo+Platelet Transfusion
L-PLUS 1 and L-PLUS 2 (UEGW2018)	Phase 3	Thrombocytopenia \| Chronic liver disease	427	Lusutrombopag 3 mg	(pxflecelkk) = qcmczxqqrl azpudfiqsx (nwayjdazfa ) View more	Positive	01 Oct 2018
				Placebo	(pxflecelkk) = yendyljcsg azpudfiqsx (nwayjdazfa ) View more
NCT02389621 (L-PLUS 2, CTgov)	Phase 3	Thrombocytopenia \| Chronic liver disease	215	Lusutrombopag (Lusutrombopag)	hnmvbwypmu(roazlmfyvp) = lvayodpkyz jakpmrpuga (hrtjirgfpq, shgzrysiek - zeldvcapzn) View more	-	25 Sep 2018
				Placebo (Placebo)	hnmvbwypmu(roazlmfyvp) = bwzfllbrkz jakpmrpuga (hrtjirgfpq, pmqasscgfx - uhexoffgpc) View more