By Caicai
The festive atmosphere has become increasingly strong as the Chinese New Year is approaching, and there has been good news in the pharmaceutical circle in China: the Patent Reexamination Board of the State Intellectual Property Office of China has recently announced the composition patent examination results of Novartis’ billion-USD blockbuster drug Entresto (sacubitril/valsartan sodium tablets, LCZ696): "Patent fully declared invalid" for the invention Pharmaceutical compositions comprising valsartan and NEP inhibitors of the patentee Novartis on the ground of inventiveness problem. In other words, the patent portfolio of this heart failure "miracle drug" Entresto that has been marketed in China just in 2017 is officially broken through, and the chance for Chinese generic drug enterprises has come.
Past and present of the "most encouraging" heart failure "miracle drug" Entresto over the 20 years
Heart failure’s main manifestation is insufficient blood pumping of heart, and it is a potentially deadly disease of which most patents need life-long treatment. Before Entresto, the most popular therapeutic regimen for heart failure is the "Golden Triangle Regimen", namely, angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) + aldosterone receptor antagonist + β-receptor blocker, mainly used to regulate the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS), wherein, the representative drug of ACEI is enalapril, and the representative drug of ARB is valsartan. However, the effects of SNS-RAAS against heart failure are not satisfactory, with high mortality: about 50% patients die 5 years after the diagnosis. There was no remarkable progress in the heart failure field in more than a decade.
Entresto is the world’s first ARB-NEP (neprilysin) inhibitor, with the active ingredient of sacubitril and valsartan sodium, being a sodium salt crystal complex combined by 1:1 molar ratio of the two "old drugs": the ARB valsartan and the NEP inhibitor sacubitril, with the former blocking the angiotensin II receptor blocker in RAAS, and the latter’s metabolite inhibiting NEP, functioning as vasodilation, prevention and reversal of cardiovascular remodeling, and natriuresis, etc. It has significant therapeutic advantages over the existing heart failure drugs.
The drug was approved by the U.S. FDA in July 2015, and approved by the EU in November of the same year; it obtained the top Class I recommendation in the new Guideline for the Management of Heart Failure issued by the American College of Cardiology (ACC), American Heart Association (AHA), Heart Failure Society of America, and European Society of Cardiology (ESC) in 2016, and is called the "most encouraging" heart failure drug in the past 20 years. Entresto was filed the marketing application to the CFDA in February 2016, and was included in the priority review by the CDE in December of the same year by reason of "having significant therapeutic advantages compared to existing treatment means". Entresto (the trade name in Chinese: 诺欣妥) was officially approved for marketing in China by CFDA in July 2017, for adult chronic heart failure patients with reduced ejection fraction, to reduce their risks of cardiovascular death and heart failure hospitalization.
There are about 60 million heart failure patients in the world, with the morbidity in the population aged above 45 of 3-5%. According to a large epidemiological survey in 2003, the prevalence of heart failure in adults in mainland China reached 0.9%, with about 4.50 million heart failure patients, meaning that the market potential is tremendous. According to the financial report of Novartis, the sales revenue of the drug was USD 170 million in 2016, and grew to USD 322 million in the first 3 quarters of 2017; the figures were not as high as expected, but already showed the strong growth momentum. An industry analyst forecast that the annual sales peak of the drug might exceed USD 5 billion, and app...
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