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    Home > Medical News > Latest Medical News > Analysis of PAH therapeutic drugs: Nanjing Warwick is a black horse, which has started to develop independently in China

    Analysis of PAH therapeutic drugs: Nanjing Warwick is a black horse, which has started to develop independently in China

    • Last Update: 2016-12-21
    • Source: Internet
    • Author: User
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    Pulmonary hypertension Hypertention (PAH) refers to a hemodynamic and pathophysiological state in which the pulmonary artery pressure increases beyond a certain critical value Its diagnostic standard is that the mean pulmonary artery pressure (PAPM) measured by the right cardiac catheter is ≥ 25mmhg in the state of sea level rest It is mainly characterized by progressive increase of pulmonary vascular resistance and pulmonary artery pressure caused by pulmonary artery occlusion, accompanied by irreversible pulmonary vascular weight Structure, eventually leading to right heart failure and death, the patient due to long-term hypoxia resulting in cyanosis of the lips and is known as "blue lips." 1、 In the mid-1990s, the first PAH treatment drug Flolan was approved by FDA, which opened the drug targeted treatment of PAH and solved the dilemma of no drugs available for PAH Up to now, with the in-depth study of the pathogenesis of PAH, a variety of selective pulmonary vasodilators have been successfully developed, mainly including: (1) calcium channel blockers (CCBS): nifedipine, amlodipine, diltiazem; (2) prostacyclin and its structural analogues: epoprost sodium, traprostil, iloprost, beprost sodium; (3) Endothelin receptor antagonists: bosentan, alisentan, and maxitetan; (4) phosphodiesterase-5 (PDE-5) inhibitors: sildenafil, Tadanafil; (5) guanosine cyclase (SGC) agonist: lyoxyqua; (6) cycloprostaglandin receptor agonist: selexipag CCBs is only effective for a few patients with positive response to acute pulmonary vasodilation test, and it is inconvenient to use, not a good PAH drug The decrease of prostacyclin level is an important pathogenesis of PAH, so prostacyclin and its structural analogues are the representatives of PAH drugs As mentioned above, although epoprost sodium is the first PAH treatment drug approved by FDA in the United States, its clinical application is limited due to its own characteristics and side effects Among the four prostacyclin and its structural analogues for PAH treatment, except for the oral preparation of beprost sodium, the other three are injection or inhalation solution, which is inconvenient for long-term administration, but beprost sodium is only suitable for the early treatment of PAH The long-term administration of prostacyclin was not realized until December 2013, when the FDA approved the troprostanil sustained-release tablets developed by the United treatment company of the United States Bosentan, approved by FDA in 2001, is the first oral endothelin receptor antagonist for the treatment of PAH Then FDA approved the same drug in 2007 Endothelin receptor antagonists are popular in clinic because of their advantages of convenient administration and less complications Up to now, they have been the key varieties in the treatment of PAH, especially opsumit, a dual endothelin receptor antagonist approved by FDA in 2013 The safety, tolerance and permeability of macititam were good, and its tissue targeting was better than other endothelin receptor antagonists When the concentration was lower than 10 times of bosentan, macititam had the same antihypertensive effect, and the duration of action was 2 times of bosentan PDE-5 inhibitors are mainly used in the treatment of erectile dysfunction (ED) in men and are also developed for the treatment of PAH Sildenafil and Tadanafil have both been imported into China, but because the domestic ED market is far larger than the PAH market, the imported dosage forms and specifications are only applicable to the treatment of ED, and there is no dosage forms and specifications for the treatment of PAH (at present, the imported Tadanafil only has hierlich for the treatment of ED, there is no adcirca for the treatment of PAH; sildenafil only has Viagra for the treatment of ED, there is no revatio for the treatment of PAH) In 2013, the U.S FDA approved the guanosine cyclase (SGC) agonist drug, adempas, for the treatment of PAH The drug has the effects of vasodilation and anti vascular remodeling It is not only effective for PAH, but also suitable for CTEPH treatment In 2015, selexipag (uptravi), a prostacyclin IP receptor agonist, was approved by the US FDA to be used in the treatment of PAH Selexipag can improve the function of vascular endothelial cells, reduce the hypertrophy of pulmonary artery wall, and reduce the right ventricular systolic pressure, so as to improve the survival rate of patients with PAH The drug was also approved for market in the European Union in May this year 2、 Analysis of PAH treatment drug market sales of PAH treatment drugs in 2014 and 2015 are shown in the table below Bosentan is still the top one in sales, and the biggest increase in sales is macitentan Both drugs belong to actelion company Actelion is a Swiss biopharmaceutical company founded by 4 scientists of Roche It is dedicated to the research and development of rare disease drugs, and it is a unique company in the field of pulmonary hypertension There are five listed PAH treatment drugs (ventavis, traceer, opsumit and uptravi), of which opsumit and uptravi are highly respected The total sales volume is expected to exceed 4 billion US dollars by 2020, and according to analysts' prediction, the total sales volume of these two drugs in 2020 is more likely to exceed 4.6 billion US dollars Recently, the pharmaceutical giant Johnson & Johnson failed to purchase actelion for $26 billion As early as last June, actelion refused to purchase shire for $18.9 billion According to a report by the Wall Street Journal, actelion's transaction with Sanofi can bring its market value close to $30 billion, which is enough to show the speed of its market value soaring and the attention of major pharmaceutical giants to its rare disease drugs Novartis' PAH drug qcc374 has completed phase 1 clinical trials in 2014, and only registered phase 2 clinical trials in October this year, which is still in the state of recruitment 3、 Domestic import, independent R & D and imitation of PAH therapeutic drugs In April 2006, CFDA approved ventavis, the first drug for PAH treatment, to be listed in China Up to now, it has approved 5 kinds of PAH treatment drugs (iloprost inhalation solution, troprostil injection, beprost sodium tablet, bosentan tablet and alisentan tablet), among which beprost sodium tablet has been localized (produced by Beijing Taide Pharmaceutical Co., Ltd., trade name "kaina"), and the other 4 kinds are still in accordance with the It's expensive to import Maxitetan, leopard and selexipag have also submitted import registration to CFDA and have obtained clinical approval With the development of new drugs in China in recent years, enterprises in China have begun to develop PAH drugs Tpn171 is the first new drug independently developed for the treatment of pulmonary hypertension in China Shandong tepharman Pharmaceutical Co., Ltd has applied for raw materials, and Shanghai Institute of medicine, Chinese Academy of Sciences has applied for preparations In February this year, tpn171 has been approved for clinical application (Table 1) Table 1: registration and application of tpn171 The patent of bosentan has expired in November 2015 The core patents of the three drugs with the most clinical advantages and prospects in PAH treatment (maxitetan, lyoxygenase and selexipag) in China are shown in Table 2 Table 2: the core patents of masetiptan, lioxigua and selexipag in China are very popular to imitate PAH treatment drugs in China In addition to selexipag and iloprost, other pharmaceutical companies, such as epoprost sodium, tripprostil, bosentan, alisentan, maxietiptan and lioxigua, have submitted applications to CFDA and obtained clinical approval (as shown in table 3) Among them, Nanjing Huawei Pharmaceutical (maxitetan tablets and lioxigua tablets as well as APIs), Jiangsu Haosen Pharmaceutical (maxitetan tablets, anlishentan tablets) and Lianyungang hongchuang Pharmaceutical (maxitetan, anlishentan APIs) have developed two kinds of PAH treatment drugs respectively From the comprehensive factors such as the declared products, Nanjing Huawei pharmaceutical has more advantages Table 3: PAH drug domestic registration application data source: drug intelligence data note: This article is original by the author of drug intelligence network, welcome to reprint, please indicate the source and author when reprinting, thank you!
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