New Zealand Green, a recombiner of Zesheng pharmaceutical, is expected to be approved in China

Wen Jie DOPINE On January 16, Shanghai Zesheng Pharmaceutical Co., Ltd changed the listing application of Newland green, a recombinant human for injection, into the "in approval" state, indicating that the international first genetic engineering biological innovative drug for chronic heart failure treatment is expected to be approved for listing in China RhNRG-1 for injection is a recombinant protein drug independently developed by Zesheng pharmaceutical and the world's first for the treatment of chronic heart failure and other diseases It is derived from the active peptide fragment of nuregulin-1 naturally existing in human body, with a total length of 61 amino acids The gene fragment was inserted into bacterial gene by gene recombination technology, and expressed in bacteria to synthesize the protein fragment After purification, the bioactive medicinal protein was obtained Neucardin ® is the first in class new drug in the world that directly acts on cardiomyocytes to treat chronic heart failure by NRG1 / ErbB new mechanism of action It can directly bind with ErbB4 receptor on cardiomyocyte membrane, and mediate the formation of ERBB2 / ErbB4 heterodimer, while erbB2 / ErbB4 heterodimer can activate a series of downstream signal pathways in cardiomyocytes and change the related protein Expression and regulation, and then directly repair the structure of myocardial cells, improve cardiac function Among them, the signaling pathways in cardiomyocytes activated by neucardin include: ① increasing cardiac specific myosin light chain kinase, The expression of cmlck leads to the phosphorylation of myosin light chain (mlc2v), which promotes the reorganization of sarcomere and contraction unit, improves the structure of myocardium and the function of systole and diastole; The phosphorylation of PLB can activate sarcoplasmic reticulum Ca2 + - ATPase (SERCA2a), regulate Ca2 + circulation, and improve the systolic and diastolic function of the heart In addition, neucardin ® may play a role by regulating the fatty metabolism related enzymes of cardiomyocytes, improving the oxygen efficiency of energy metabolism and other mechanisms Heart failure is a complex clinical syndrome caused by the change of myocardial structure and function, which leads to the low function of ventricular ejection and / or filling It is a common terminal stage of many heart diseases, and also a disease with high morbidity and mortality According to left ventricular ejection fraction (LVEF), heart failure can be divided into heart failure with reduced ejection fraction (hfref, commonly known as "systolic heart failure") and heart failure with preserved ejection fraction (HFPEF, commonly known as "diastolic heart failure") At present, there are more than 23 million people suffering from this disease in the world, of which 50% are systolic heart failure and 50% are diastolic heart failure, and the five-year mortality rate of these two types of heart failure is close to 50% Chronic heart failure (CHF) refers to the persistent state of heart failure At present, the drugs used to treat CHF mainly include diuretics, ACEI, β - blockers, ARB and so on The mechanism of action is mainly sodium excretion and diuresis, vasodilation, heart rate reduction and so on Although the existing drugs can improve the symptoms of CHF and improve the survival rate of patients, the mortality rate of patients is still high, and the treatment effect is not ideal How to repair damaged cardiomyocytes to treat CHF is a long-term medical problem that scientists are committed to solve So far, there is no drug that can directly improve the structure and function of myocardial cells to treat heart failure The completed clinical trial shows that neucardin ® can improve the heart function, improve the long-term prognosis and reduce the mortality of patients with chronic systolic heart failure, especially significantly reduce the annual all-cause mortality of patients with mild to moderate heart failure (NYHA II-III, NT proBNP ≤ 1600 fmol / ml) In view of the clinical safety of neucardin ® and its effectiveness for chronic systolic heart failure (NYHA II-III, NT proBNP ≤ 1600 fmol / ml), Zesheng pharmaceutical has applied to nmpa in May 2018 for the conditional listing of neucardin ® in China, and promised to continue clinical trials to further verify the effectiveness of neucardin ® for chronic systolic heart failure Moreover, in January 2019, the conditional listing application of neucardin ® for chronic systolic heart failure was accepted by CDE, and in March 2019, it was included in the priority review scope by CDE At present, neucardin ® has registered 3 clinical trials in China, as shown in the table below In addition, neucardin ® has also been developed for the treatment of chronic diastolic heart failure and acute myocardial infarction At present, Zesheng pharmaceutical has completed the preclinical study on the indications of neucardin ® for chronic diastolic heart failure, and plans to launch the clinical phase II trial of the indications of chronic diastolic heart failure in China in early 2020, while the indications of its acute myocardial infarction are in the preclinical study stage In addition, neucardin ® is also one of the few first in class innovative sources, targets, mechanisms and mechanisms in the "11th Five Year Plan" and "12th Five Year Plan" national major new drug creation projects At present, neucardin ® has applied for 118 patents in the world, and has obtained patents in China, the United States, Europe, Japan, Australia, Russia and other major countries and regions It has obtained 41 patents and a strict and perfect intellectual property protection system It is worth mentioning that in August 2019, the FDA awarded neucardin ® the fast track qualification for chronic heart failure reference material: