The future of anti-hydranting, one hundred-year-old sic-variety and four heavy-duty drugs, is still promising.

Not long ago, Nature Reviews Drug Discovery summarized the state of thrombosis drugs in research, in fact, each year the high-impact factor journal will analyze the direction of the blood clot sediton of the drug summary, enough to see the damage to human health thrombosis! So far, the thrombosis field has produced 100-year-old drug, 2 billion varieties, 4 heavy drugs, as well as many into the clinical stage of the reserve force, the market capacity can not be underestimated!!! Centennial Drug and Landing the Moon: Aspirin "If you're on a desert island, if you choose to carry a certain drug with you, then the most likely thing to think of is aspirin..." Aspirin, penicillin, stability, known as the three classic masterpieces of medical history, the birth of the drug "Aspirin" in 1897, has been more than 120 years of history, "simple" anti-heat, analgesic, anti-inflammatory effect, has been in people's daily life no one knows, and more important anti-platelet effect, so that it obtains more important adaptation of cerebrovascular disease secondary prevention and high-risk patients of the first prevention, now has become the daily prevention of elderly patients.
aspirin, its development company Bayer, after 3 centuries of development, is still the world's top pharmaceutical company, like its classic drug aspirin, as long as it does!Figure 1: Bayer's Aspirin (Image Source: 10 billion levels: clopidogrel and apixaban clopidogrel, Polevi, is a household name for P2Y12 receptor antagonists - antiplatelet drugs.
since the listing, the original research varieties are still heavyweight-grade varieties, and in 2009 and 2011 the global sales are close to 10 billion U.S. dollars, but the so-called "both Yu Shengliang", in the same year as the cardiovascular field of the drug "Lipto", for many years occupied the global sales position, so that Boliwei can only be in the list of eye or flower position.
however, although there is no title in the international market, but with years of high added value, the original research manufacturer Sanofi is also the result of the pot full of money.
at the same time, in the Chinese market, clopidogrel has been for many years to obtain the domestic small molecular drug sales crown, on behalf of the enterprise Xinlitai also because of the pillar variety, won years of capital accumulation, for the follow-up cardiovascular field drug layout, and the development of innovative drugs, laid a solid foundation.
Figure 2: Domestic clopidogrel important imitation varieties - Teja (Image Source) Apixaban, for thrombosis field in recent years another breakthrough of 10 billion u.S. dollars of small molecule drugs, unlike the predecessor of clopidogrel is, 1) for the treatment of venous thrombosis; 2) successfully ascended to the top of the small molecule drug sales crown.
, but equally inthewise, the peak of clopidogrel met Lipto, while apixaban caught up with the overall boom of macromolecule drugs.
however, or to say a few words about apixaban, as an FXa inhibitor, especially on the basis of representing the drug Levachaban, can achieve a breakthrough upgrade, and for 2018/2019 into the small molecule drug sales crown, a large number of anti-tumor drugs left behind, BMS company's development strategy, can definitely be written into the textbook.
PS: BMS is also involved in the commercialization of Porivi!Figure 3: Apixaban's official website page (image information: ) 4 heavyweight drugs (delava/duka/Darby/Ino) NO.1: Leva chaban/2019 sales NO.10 ($6.862 billion) Levachaban, the first FXa small molecule inhibitor, the development company for Bayer, one after the introduction of the old-age predecessor Huafalin, hepatic acid momentum, and lead the market for many years.
the earliest approval time for Levatsaban is 2008, and the U.S. FDA approval time is 2011, China's approval time is 2014, the sales of the last 5 years overall steady growth, 5 years of total sales of nearly 30 billion U.S. dollars, and for many years ranked in the world's top 10 patented drug sales.
Figure 4: Levasaban's official website (picture d'Or:) NO.2: For Grillo/2019 sales of NO.83 ($1.581 billion) for Grillo, is currently considered the most likely replacement for the predecessor clopino gray, both of which are P2Y12 receptor antagonists, but gretelors are reversible, and clopires is inreversible.
The original research and development company for Grellor is AstraZeneca, the original U.S. market date was July 2011, and the indications are acute coronary syndrome (unstable angina/non-ST elevated myocardial infarction/ST-elevated myocardial infarction).
sales, it passed the $1 billion mark in 2017 and is growing slowly overall.
the variety in the domestic, in addition to AstraZeneca's original research varieties approved, Shenzhen Xinlitai's Taiyi has been approved for production, and registered as many as 30 enterprises, including Dongsun Pharmaceutical, Jiangsu Hengrui, Zhengda Tianqing, Lizhu Group and other large-scale domestic pharmaceutical enterprises.
Figure 5: Domestic for Grillo important imitation varieties - Taiyi (Image Source:) NO.3: Dabi plus group esters/2019 sales NO.86 ($1.517 billion) Bolinger Ingehan developed FIIa inhibitors, the earliest time on the market is 2008, the U.S. approval time is 2010, the U.S. approval time for selected full hip replacement surgery or knee replacement of an adult thrombosis patients approved for total joint replacement.
listing so far, although it quickly broke through the $1 billion mark, but in the past five years the global sales are between $1 billion to 2 billion, compared with the Levatshaban, not a big sell.
and the species in the domestic imitation, is sunny Dabiga group ester capsules have been approved for production in March 2020, and as the same through the consistency evaluation of the variety;
Figure 6: 3 specifications of the original Adabiga group esters (Image Source:) NO.4: Enochparin/2019 sales NO.89 ($1.492 billion) Sodium Enoxaparin, originally produced by Rhone-Poul, France Developed by Sanofi in combination with Hoechst, Germany, heparin sodium is extracted from the mucosa of the swine intestine, an elatetized heparin sodium derivative, and a low molecular amount of heparin sodium produced by alkali lysis.
low-molecular heparin clinical efficacy is superior to heparin, for the fact that, among the many low-molecular heparin drugs listed, enoxine has maintained heavy-duty sales due to its many years of efficacy.
Figure 7: Sanofi/Kesai (0.6) (Image Source) Candidate drugs are still on the way, in addition to the above-mentioned global sales of very high-selling anti-hydrant star drugs, there are also some already on the market and is often used as a control of anti-embolism drugs in the industry, such as Pragre, GP IIb/IIIa after chloratoris Assema-seine/tinfiban, PAR-1 antagonist Volapasha, Adosaban/Bequosaban after Delavaban, etc.;
Figure 8: Current antithrombotic drug targets (image source:) will next highlight the new targets and drug developments of thrombosis in a review article published in 2020 by Nature Reviews Drug Discovery, and the new progress of antiplatelets is shown in the figure below.
Figure 9: Targets for further development of current antiplatelet drugs (Image Source: ) The antiplatelet targets are mainly concentrated in PAR-1 (new antagonists do not follow the footsteps of the listed drug Volapasa), PAR-4 (BMBM) S has several drugs into the clinical stage, but progress is not very fast), PI3K beta (the target is currently on the market, but more targeted at tumors), GPVI (developed drug for macromolecular fusion protein), vWF (fastest progress to Phase II) ... The above-mentioned targets, the author believes that the development of strong or when the PAR, including PAR-1 and PAR-4, the possibility of drug-forming is relatively strong.
Figure 10: The clinical status of the ongoing antiplatelet candidate drug (Picture source: ) is naturally still carried out around the clotting waterfall, but is no longer FXa and coagulation enzymes, more direction is to target other target factors, as shown in the figure below. figure 11
: Targets for further development of current anticoagulants (Image Source: ) As shown in the figure above, the highest status of the varieties entering the development phase of fVIII targets is Phase II, the main direction of attack is TKA/THA; Period, the main direction of attack is ACS, and FXI target into the development period of the highest status of the variety is II, the difference is that the number of varieties is relatively large, FXII target into the development period of the highest status of the variety is phase II, the main attack direction is hereditary blood edema;
Figure 12: The clinical status of ongoing anticoagulant candidate drugs (Image Source: ) Summary, i.e. the general situation of drugs in the field of thrombosis.
if thrombosis is only a branch of the cardiovascular field, and the capacity of this branch is so large, then the cardiovascular field is actually still a serious impact on human health, to a certain extent, beyond malignant tumors, but, we usually link it with geriatric disease, leading to subjective negative treatment.
in recent years, the field of venous thrombosis drug development has never stalled, as mentioned above, some of the targets have been concentrated, and many are large companies in doing, even once a team, people in the layout.
and the future, will be born such as apixaban, clopidogrel and other billions of drugs, I believe the answer is yes! Ref:
Nature Reviews. DrugDiscovery.