Platelet aggregation inhibitors are in the Ascendant: tegrilol will become a "heavy bomb" in 2017. How about domestic declaration?

Although the popularity of "super heavy bomb" Plavix has been greatly reduced, it still ranks first in sales of this category with the achievement of US $1.96 billion in 2015; the follow-up excellent variety tigrew predicts that the global sales will exceed US $1 billion in 2017, becoming the family's new "heavy bomb" Clinically, platelet aggregation inhibitors can be used or are being developed for cardiovascular diseases such as antithrombotic, peripheral vascular disease, acute coronary syndrome (ACS) and pulmonary hypertension So far, there are about 29 varieties of platelet aggregation inhibitors on the market in the world According to the mechanism of drug action, platelet aggregation inhibitors can be divided into the following six categories: 1 P2Y12 receptor inhibitors (also known as adenosine diphosphate receptor antagonists); 2 Cyclooxygenase inhibitors; 3 Adenosine cyclophosphate enhancers, including prostacyclin derivatives (such as beprost) and phosphodiesterase inhibitors (such as anagrel); 4 Glycoprotein (GP Ⅱ B / Ⅲ a) antagonists; 5 Compound platelet aggregation inhibitors 6 Other platelet aggregation inhibitors More than half of P2Y12 receptor inhibitors in the global perspective According to statistics, from October 2014 to September 2015, the global market size of platelet aggregation inhibitors is about 8.8 billion US dollars In US dollars, it decreased by 7% year-on-year, and increased by 3% year-on-year at fixed exchange rate The market share of various platelet aggregation inhibitors is shown in Figure 1, in which P2Y12 receptor inhibitors account for 54%, more than half of the total The largest market size of Asia / Africa / Australia is analyzed by four regions in the world See Figure 2 for market size (ball), market share and year-on-year growth rate from October 2014 to September 2015 The market size of Asia / Africa / Australia is the largest, reaching US $4.15 billion, a year-on-year decrease of 7%, a year-on-year increase of 3% based on fixed exchange rate; Japan is the largest national market, about US $2 billion, a year-on-year decrease of 16%, a year-on-year decrease of 2% based on fixed exchange rate; China's market size is about US $1.1 billion, a year-on-year increase of 10%, a year-on-year increase of 10% based on fixed exchange rate In the European market, France is US $330 million, down 23% year on year, down 9% year on year in terms of fixed exchange rate; Italy is US $300 million, down 12% year on year, up 5% year on year in terms of fixed exchange rate In North America and Europe, the U.S market is 1.7 billion US dollars, up 6% year-on-year, in fixed exchange rate terms, up 6% year-on-year; in Canada, 130 million US dollars, down 18% year-on-year, in fixed exchange rate terms, down 7% year-on-year In Latin American market, Venezuela is US $240 million, a year-on-year increase of 47%, in fixed exchange rate terms, a year-on-year increase of 47%; Brazil is US $220 million, a year-on-year decrease of 16%, in fixed exchange rate terms, a year-on-year increase of 9% It is worth noting that during October 2013 to September 2014 and October 2014 to September 2015, the U.S dollar index increased by 16% on average, and most currencies depreciated after converting the U.S dollar with floating exchange rate Therefore, the year-on-year ratio based on fixed exchange rate is more representative of the actual consumption level of drugs in the market (assuming that the drug price remains unchanged) During this period, the exchange rate of RMB to us dollar has not changed much, so the market data of China and the United States reflect the actual level of drugs consumed in the market Tegrilol will become a "blockbuster" in the global leading brand of platelet aggregation inhibitors or generic drugs (see Table 1) Although the annual sales amount of Sanofi's "super blockbuster" Plavix has decreased from $9.9 billion in 2011 to $1.96 billion in 2015, the product still ranks first in the sales amount of platelet aggregation inhibitors Tegrilol, a superior subsequent product of clopidogrel, was the first P2Y12 receptor antagonist with reversible binding, direct acting and oral administration On July 20, 2011, the FDA approved tegrarol to reduce the incidence of thrombotic cardiovascular events in patients with ACS Compared with clopidogrel, tegrarol has faster effect and stronger inhibition on platelet aggregation, which can significantly reduce the incidence of cardiovascular death, myocardial infarction or stroke At the same time of effective treatment, tegrarol did not significantly increase the incidence of major bleeding events It is predicted that in 2017, the global sales of tegrilo will exceed US $1 billion On November 22, 2012, China approved the import of tegrilol tablets, with the trade name of Belinda As of January 2016, 31 domestic companies have submitted drug registration applications for tegrilol as a new chemical drug of category 3.1, 16 of which have been approved for clinical application, 2 have not been approved for clinical application, and 13 are in review status; 16 of tegrilol tablets (imitation, chemical drugs of category 6) have been approved for clinical application, and 13 have been approved for clinical application The application for drug registration has been submitted for review; one of tegrilol dispersible tablets (chemical medicine 5 new drugs) has submitted the application for drug registration, which is under review It is expected that antiplatelet drugs are very important in the treatment of ACS Clopidogrel or prasugrel or tigril can further reduce the risk of cardiovascular events in patients with ACS This dual antiplatelet therapy is the current standard However, the current dual antiplatelet drugs are not perfect The disadvantage of these drugs is that the oral administration leads to the slow onset and failure of antiplatelet effect, which is a problem for ACS patients who need emergency surgery Therefore, it is always expected to produce platelet aggregation inhibitors with rapid effect Cangrelor, a P2Y12 receptor inhibitor, was created by AstraZeneca and licensed to medicine for research and development The drug has direct effect and reversible effect, fast effect and failure, and can be used for intravenous administration In March 2015 and June 2015, the European EMA and the U.S FDA respectively approved the use of cangreleo for injection About 15 domestic trends The varieties of platelet aggregation inhibitors have been purchased in 22 sample hospitals in China, including: 1 Clopidogrel tablets; 2 Aspirin tablets; 3 Beprost tablets; 4 Compound dipyridamole ginkgo injection; 5 Ozagrel injection; 6 Cilostazol tablets and capsules; 7 Tirofiban injection; 8 Tegrilol tablets; 9 Salgrel ester tablets; 10 Aluminum magnesium aspirin tablets（ Aspirin + glycyrrhizin + magnesium carbonate); 11 Dipyridamole tablets; 12 Indobufen tablets; 13 Etibatide injection; 14 Compound aspirin dipyridamole tablets and capsules; 15 Ticlopidine tablets and capsules Clopidogrel tablets are increasing year by year The purchase amount of clopidogrel tablets in sample hospitals is increasing year by year See Figure 3 for the trend From 2005 to 2015, the compound annual growth rate was 29.8%, which slowed down significantly in the past three years It is estimated that the purchase amount of clopidogrel sample hospital in 2015 will reach 1.7 billion yuan, accounting for about 72% of the purchase amount of platelet aggregation inhibitors The main suppliers are Sanofi Minsheng (accounting for 53% of the market share of clopidogrel tablets) in Hangzhou and xinlitai (31%) in Shenzhen See Figure 4 for the trend of purchase amount of other major platelet aggregation inhibitors except clopidogrel tablets in other sample hospitals The compound annual growth rate from 2005 to 2015 was 17.1% It is estimated that in 2015, the total purchase amount of other 10 varieties of sample hospitals is about 650 million yuan, accounting for about 28% of the purchase amount of platelet aggregation inhibitors The purchase amount of Ozagrel injection sample hospital peaked in 2011 and was a "discount point", from 210 million yuan (Liaoning Dandong Pharmaceutical Co., Ltd accounted for 50% of Ozagrel injection market share, Shandong Hualu Pharmaceutical Co., Ltd accounted for 11%) to 36.77 million yuan in 2015 (Shandong Hualu Pharmaceutical Co., Ltd accounted for 31%, Liaoning Dandong Pharmaceutical Co., Ltd accounted for 14% of Ozagrel injection market share) Aspirin tablets have experienced a hundred years of vicissitudes and have been enduring for a long time, which is related to the two combinations of drugs recommended in various anti platelet aggregation treatment guidelines, as well as the known exact effects of aspirin, such as antipyretic, analgesic, anti-inflammatory, anti rheumatic, prevention of myocardial infarction, and Prevention of stroke There are many areas that are still under study, such as anti-cancer, anti hypertension, renal protection, treatment of some eye diseases, and auxiliary treatment of diabetes It is worth thinking deeply that, according to the data of aspirin tablets purchased by sample hospitals in 2015, about 35 domestic enterprises have purchased aspirin tablets in sample hospitals However, the total purchase amount of these 35 companies only accounts for 2.3% of the total purchase amount of aspirin tablets, while the subtotal amount of Bayer (Germany) and Bayer healthcare (Italy) Co., Ltd accounts for 97.7% The increase and decrease of the purchase amount of other main varieties of sample hospitals are basically consistent with the anti platelet aggregation treatment guidelines and drug use trends of mainstream pharmaceutical market countries.