An incident happened to the representative heart disease products with TCM characteristics several days ago, which attracted broad attention of the industry. Therefore, I hereby focus on blockbuster products in the future heart disease drug market, and regard the heart failure product Entresto® of Novartis as the foremost, which will not only be the absolute dominant of the future heart failure drug market, but also the leader of the future heart disease drug market.
I. Numerous patients with chronic heart failure (CHF) that causes heavy medical burden
CHF is the severe and end stage of various cardiovascular diseases, with high morbidity and mortality and poor prognosis, being one of the diseases seriously threatening human health at present.
CHF is a disease that causes ventricular filling and ejection function impairment and eventually causes low ventricular blood pumping function due to various causes. According to the current statistical results, the morbidity of CHF in global population aged above 45 is 3-5%, and this figure may be higher in reality. World FS Society estimated the prevalence of CHF to be 2.5% in the West. The heart failure is also an important and increasingly severe public health problem, with global funds spent on heart failure of USD 108 billion every year, wherein, the hospitalization expenses account for 60%-70% of the treatment expenses.
In 2006, the American Heart Association estimated that Americans with heart failure approached 5.80 million, and predicted the patient population to increase by about 50% to reach over 8 million by 2030. Over 1 million people with heart failure need hospitalization in the U.S. and Europe every year. The prevalence of heart failure in Chinese adults is 0.9% and the patient population is at least 7 million, with high case fatality rate and poor prognosis. The heart failure treatment rate and control rate in China are still far lower than those in developed countries despite years of efforts.
II. Double-effect mechanism of action of Entresto®
Entresto® (Sacubitril/valsartan tablets, LCZ696) is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) developed by Novartis and approved for marketing on July 7, 2015 and November 19, 2015 separately by the U.S. Food and Drug Administration (FDA) and the EU for treating heart failure patients with reduced ejection fraction.
Novartis announced on July 28, 2017 that Entresto® was formally approved by CFDA for marketing to treat adult patients with CHF and reduced ejection fraction, to reduce their risks of cardiovascular death and heart failure hospitalization.
The chemical structure of Entresto® is 1:1 combination of the ARB valsartan and NEP inhibitor precursor Sacubitril, i.e., it has two action targets, with the former blocking RAAS and the latter metabolizing to LBQ657 to inhibit NEP, thereby inhibiting RAAS.
Therefore, the treatment of CHF by Entresto® mainly functions as vasodilation, prevention and reversal of cardiovascular remodeling, and natriuresis, etc. through inhibiting the angiotensin II receptor in RASS and NEP.
Inhibiting angiotensin II receptor in RASS
As an important humoral regulation system, RASS exists in the circulatory system and also vascular wall, heart, central nerve, kidney and adrenal gland, etc., to jointly participate in target organ regulation. A series of fundamental and clinical research proves that the neuroendocrine activation, especially the RASS and sympathetic nervous system activation, plays a key role in the occurrence and development of heart failure.
ARB can block RASS and function as vasodilation, blood pressure reduction, vascular endothelial cell protection, inhibition of sympathetic transmitter release, anti-atherosclerosis, and prevention and reversal of cardiovascular remodeling, etc. ARB can be used to treat CHF, and can continuously improve hemodynamics and prevent CHF aggravation, wherein, the valsartan is the ARB representative, and one of the clinically most commonly used drugs for hypertension and CHF, etc.
Inhibiting NEP
NEP (Neutral...
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