Delving into the Latest Updates on Recombinant human neuregulin-1 (Zensun (Shanghai)) with Synapse

Overview

Basic Info

Drug Type

Recombinant polypeptide

Synonyms

Neucardin, RHNRG-1-BETA, Recombinant Human Neuregulin-1β

+ [4]

Target

NRG1

Mechanism

NRG1 modulators(Neuregulin-1 modulators)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Heart Failure, DiastolicChronic heart failureChronic systolic heart failure+ [2]

Inactive Indication

Chronic congestive heart failureNeurilemmomaStroke

Originator Organization

Zensun (Shanghai) Sci & Tech Co., Ltd.

Active Organization

Zensun (Shanghai) Sci & Tech Co., Ltd.

Zensun Enterprises Ltd.

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

RegulationSpecial Review Project (CN)

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[Translation] A phase III clinical trial of multicenter, randomized, double-blind, placebo-controlled parallel-group study based on standard treatment to evaluate the effects of recombinant human neuregulin for injection on cardiac function and reversal of ventricular remodeling in patients with chronic systolic heart failure

评价注射用重组人纽兰格林对男性 NT-proBNP ≤ 1700 pg/ml 以及女性 NT-proBNP ≤ 4000 pg/ml，纽约心功能分级 II-III 级慢性收缩性心力衰竭患者的心功能及逆转心室重构的影响，确证其疗效和安全性。

[Translation]

To evaluate the effects of recombinant human neuregulin for injection on cardiac function and reverse ventricular remodeling in patients with chronic systolic heart failure (NT-proBNP ≤ 1700 pg/ml in males and NT-proBNP ≤ 4000 pg/ml in females) and New York Heart Association functional class II-III, and to confirm its efficacy and safety.

Start Date04 May 2023

Sponsor / Collaborator

Zensun (Shanghai) Sci & Tech Co., Ltd.

NCT05949801 / RecruitingPhase 3

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial Based on Standard Treatment to Evaluate the Effect of Injectable Neucardin on Cardiac Function and Reverse Ventricular Remodeling in Patients With Chronic Systolic Heart Failure

A multicenter, randomized, double-blind, placebo-controlled phase III clinical trial to evaluate the effect of recombinant human Neuregulin-1 for injection on cardiac function and reverse ventricular remodeling in male patients with NT-proBNP ≤ 1700 pg/ml and female patients with NT-proBNP ≤ 4000 pg/ml and New York Heart Association class II-III chronic systolic heart failure, and to confirm its efficacy and safety.

Start Date13 Apr 2023

Sponsor / Collaborator

Zensun (Shanghai) Sci & Tech Co., Ltd.

CTR20192276 / RecruitingPhase 2

随机、双盲、安慰剂平行对照评价注射用重组人纽兰格林对射血分数保留心力衰竭(HFpEF) 患者安全性和有效性临床试验

[Translation] A randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of recombinant human neuregulin for injection in patients with heart failure with preserved ejection fraction (HFpEF)

随机、双盲、安慰剂平行对照评估注射用重组人纽兰格林对射血分数保留心力衰竭患者(LVEF≥50%)的疗效，并进行安全性评价。

[Translation]

A randomized, double-blind, placebo-controlled parallel study was conducted to evaluate the efficacy of recombinant human neuregulin for injection in patients with heart failure with preserved ejection fraction (LVEF ≥ 50%) and to assess its safety.

Start Date03 Nov 2022

Sponsor / Collaborator

Zensun (Shanghai) Sci & Tech Co., Ltd.

100 Clinical Results associated with Recombinant human neuregulin-1 (Zensun (Shanghai))

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100 Translational Medicine associated with Recombinant human neuregulin-1 (Zensun (Shanghai))

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100 Patents (Medical) associated with Recombinant human neuregulin-1 (Zensun (Shanghai))

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36

Literatures (Medical) associated with Recombinant human neuregulin-1 (Zensun (Shanghai))

01 Feb 2024·Journal of Molecular and Cellular Cardiology

RETRACTED: The novel antibody fusion protein rhNRG1-HER3i promotes heart regeneration by enhancing NRG1-ERBB4 signaling pathway

Article

Author: Wang, Xuemei ; Wu, Hao ; Fu, Wenbin ; Tang, Luxun ; Zeng, Chunyu ; He, Yanji ; Wang, Wei Eric

Stimulating cardiomyocyte proliferation in the adult heart has emerged as a promising strategy for cardiac regeneration following myocardial infarction (MI). The NRG1-ERBB4 signaling pathway has been implicated in the regulation of cardiomyocyte proliferation. However, the therapeutic potential of recombinant human NRG1 (rhNRG1) has been limited due to the low expression of ERBB4 in adult cardiomyocytes. Here, we investigated whether a fusion protein of rhNRG1 and an ERBB3 inhibitor (rhNRG1-HER3i) could enhance the affinity of NRG1 for ERBB4 and promote adult cardiomyocyte proliferation. In vitro and in vivo experiments were conducted using postnatal day 1 (P1), P7, and adult cardiomyocytes. Western blot analysis was performed to assess the expression and activity of ERBB4. Cardiomyocyte proliferation was evaluated using Ki67 and pH 3 immunostaining, while fibrosis was assessed using Masson staining. Our results indicate that rhNRG1-HER3i, but not rhNRG1, promoted P7 and adult cardiomyocyte proliferation. Furthermore, rhNRG1-HER3i improved cardiac function and reduced cardiac fibrosis in post-MI hearts. Administration of rhNRG1-HER3i inhibited ERBB3 phosphorylation while increasing ERBB4 phosphorylation in adult mouse hearts. Additionally, rhNRG1-HER3i enhanced angiogenesis following MI compared to rhNRG1. In conclusion, our findings suggest that rhNRG1-HER3i is a viable therapeutic approach for promoting adult cardiomyocyte proliferation and treating MI by enhancing NRG1-ERBB4 signaling pathway.

01 Sep 2023·JACC. Basic to translational science

Neuregulin-1β Improves Uremic Cardiomyopathy and Renal Dysfunction in Rats.

Article

Author: Kovács, Ferenc ; Krenács, Tibor ; Lauber, Gülsüm Yilmaz ; Kővári, Bence ; Kovács, Zsuzsanna Z A ; Sárközy, Márta ; Podesser, Bruno K ; Zins, Karin ; Csont, Tamás ; Cserni, Gábor ; Abraham, Dietmar ; Siska, Andrea ; Watzinger, Simon ; Monostori, Péter ; Márványkövi, Fanni ; Pokreisz, Peter ; Galla, Zsolt ; Fintha, Attila ; Kriston, András ; Szűcs, Gergő ; Szabó, Gábor Tamás ; Kiss, Attila ; Szabó, Petra Lujza ; Horváth, Péter ; Acar, Eylem ; Földesi, Imre

Chronic kidney disease is a global health problem affecting 10% to 12% of the population. Uremic cardiomyopathy is often characterized by left ventricular hypertrophy, fibrosis, and diastolic dysfunction. Dysregulation of neuregulin-1β signaling in the heart is a known contributor to heart failure. The systemically administered recombinant human neuregulin-1β for 10 days in our 5/6 nephrectomy-induced model of chronic kidney disease alleviated the progression of uremic cardiomyopathy and kidney dysfunction in type 4 cardiorenal syndrome. The currently presented positive preclinical data warrant clinical studies to confirm the beneficial effects of recombinant human neuregulin-1β in patients with chronic kidney disease.

01 Jul 2023·American journal of cardiovascular drugs : drugs, devices, and other interventions

Safety, Tolerability, and Pharmacokinetics of Recombinant Human Neuregulin-1 in Healthy Chinese Subjects.

Article

Author: Cui, Yimin ; Meng, Lei ; Zhou, Mingdong ; Sun, Peihong ; Zhao, Xia ; Wang, Xiaorui ; Zhou, Ying ; Qin, Xiaoyan ; Xu, Junyu

BACKGROUNDWe investigated the safety, tolerability, and pharmacokinetics of intravenous recombinant human Neuregulin-1 (rhNRG-1), a DNA recombinant protein for the treatment of chronic heart failure, in healthy Chinese volunteers following single and multiple dose administration.METHODS AND RESULTSTo evaluate the safety and tolerance after single-dosing escalation, 28 subjects were divided into six groups (0.2, 0.4, 0.8, 1.2, 1.6, and 2.4 μg/kg) to receive an intravenous (IV) infusion of rhNRG-1 over 10 min by a randomized, open-label design. Only the 1.2 μg/kg dose group obtained pharmacokinetic parameters: C_max was 7.645 (24.21) ng/mL, AUC_0-t was 97.088 (21.41) min·ng/mL. To assess the safety and pharmacokinetics after multiple-dosing, 32 subjects were divided into four groups (0.2, 0.4, 0.8, and 1.2 μg/kg) to receive a 10-min IV infusion of rhNRG-1 for five consecutive days. After multiple dosing of 1.2 μg/kg, the C_max value at day 5 was 8.838 (51.6) ng/mL and the AUC_0-t value at day 5 was 109.890 (32.99) min·ng/mL. RhNRG-1 is rapidly cleared from the blood and has a short t_1/2 of about 10 min. The adverse events related to rhNRG-1 mainly included flat or inverted T wave and gastrointestinal reactions, all of which were mild.CONCLUSIONSIt is concluded that rhNRG-1 is safe and well tolerated in healthy Chinese subjects at the dosing levels used in this study. The severity and frequency of adverse events did not increase with the prolongation of administration time.CLINICAL TRIAL REGISTRATIONChinese Clinical Trial Registry ( http://www.chictr.org.cn ) Identifier No. ChiCTR2000041107.

100 Deals associated with Recombinant human neuregulin-1 (Zensun (Shanghai))

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Heart Failure, Diastolic	Phase 3	US	Zensun Enterprises Ltd.	30 Jan 2022
Chronic heart failure	Phase 3	CN	Zensun (Shanghai) Sci & Tech Co., Ltd.	01 Apr 2010
Chronic systolic heart failure	Phase 3	CN	Zensun (Shanghai) Sci & Tech Co., Ltd.	01 Apr 2010
Heart failure with normal ejection fraction	Phase 2	CN	Zensun (Shanghai) Sci & Tech Co., Ltd.	03 Nov 2022
Neurilemmoma	Phase 1	CN	Zensun (Shanghai) Sci & Tech Co., Ltd.	12 Mar 2020
Stroke	Phase 1	CN	Zensun (Shanghai) Sci & Tech Co., Ltd.	17 Dec 2018
Heart Failure	Phase 1	CN	Zensun (Shanghai) Sci & Tech Co., Ltd.	17 Apr 2012
Myocardial Infarction	IND Application	CN	Zensun Enterprises Ltd.	30 Jan 2022
Chronic congestive heart failure	Preclinical	CN	Zensun (Shanghai) Sci & Tech Co., Ltd.	01 Apr 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01541202 (ZS-01-305, Literature) Manual	Phase 3	Chronic heart failure	679	Neuregulin-1	lrjpwhjakp(ztxwvtgpmy) = tvcioigsrt xuvgfpxfvj (lnkcvwjpab ) View more	Positive	08 Mar 2018
				Placebo	lrjpwhjakp(ztxwvtgpmy) = jzwqzvwczu xuvgfpxfvj (lnkcvwjpab ) View more