Please Note: Blog posts are not selected, edited or screened by Seeking Alpha editors.

Analysis of drugs in the treatment of Thrombosis in China

By Tommy Tang, GBI Analyst

Antithrombotic agents (WHO ATC B01A) are currently enjoying high (above market) growth in China, with market share expected to grow even more dramatically in the next decade as the thrombosis risk increases among Chinese, due to the growing aging population and changes in diet and lifestyle.

 

Antithrombotic agents are targeted to the treatment of thrombosis, covering many diseases, from pulmonary embolism caused by deep vein thrombosis to myocardial infarction and ischemic stroke. They agents typically inhibit the formation of blood clots or actively break them down, and thus are divided to 3 main primary categories: anticoagulants, platelet aggregation inhibitors, and thrombolytics. In China, the top selling of drugs in this area belong to the anticoagulant and antiplatelet drug categories. The major drugs for the three areas are listed as below.

 

Category

Main Targets

Molecules

WHO ATC IV

Anticoagulants

Vitamin K Antagonists

Warfarin

B01AA

Acenocoumarol

Phenindione

Other coumarines

Heparin and Derivative Substances

Heparin*

B01AB

Low Molecular Weight Heparin*

Factor Xa Inhibitors

Rivaroxaban

B01AX

Direct Thrombin Inhibitors

Hirudin

B01AE

Lepirudin

Bivalirudin

Dibigatran

Argatroban

Antiplatelet Aggregation

Cyclooxygenase Inhibitors

Aspirin

B01AC

Adenosine Diphosphate Receptor

Clopidogrel*

Ozagrel*

Prasugrel

Ligustrazine

Ticlopidine

Phosphodiesterase Inhibitors

Dipyridamole

Cilostazol

Glycoprotein IIB/IIA Inbibitors

Abciximab

Eptifibatide

Tirofiban

Thrombolytics

Activating Plasminogen

Streptokinase

B01AD

Urokinase

Recombinant Plasminogen Activators

Alteplase

Retplase

Lumbrokinase

Tenecteplase

Source: GBI SOURCE and Internet

Note: * denotes top selling drugs in China

 

(1) Anticoagulants including common heparin, low molecular weight heparin (LMWH) and warfarin are often first line treatments – depending on clinical indication. Heparin typically requires close monitoring in hospitals. LMWH, as fractionated heparin, is the most popular anticoagulant due to easy manipulation and convenience – patients are not required to be monitored in the hospital when taking LMWH. In China, sales of LMWH occupied over 20% of antithrombosis drug market and it continues to be a dominant player in this market.

 

Warfarin (with brand names Coumadin, etc), another older porduct, was first registered in 1954 in china by BMS. Compared to heparin and LMWH, which should be injected, Warfarin can be used orally - a significant advantage. However, wafarin interacts with many common chemicals from medications and even foods, which make doctors difficult to determine appropriate dosing of warfarin. Many developers have tried to introduce new candidates that can replace warfarin. One example was ximelagatran (Exanta), a oral anticoagulant developed by AstraZeneca, which was withdrawn from further development due to reports of hepatotoxicity. Newer high-profile products in this field include rivaroxaban (Xarelto) developed by Bayer, and dibigatran invented by Boehringer Ingelheim. Rivaroxaban is already marketed as of 2009 in China, while Dibigatran is expected to enter the market in near future. Apixaban, another drug with a promising future, is still under development in a joint venture by Pfizer and BMS.

 

(2) Antiplatelet drugs, platelet aggregation inhibitors excl. heparin, are used to treat arterial thrombosis where anticoagulants are not effective, and thus are widely used in preventing thrombotic cerebrovascular and cardiovascular diseases. Three global top sellers in this category are are clopidogrel, ozagrel, and ligustrazine.

 

Clopidogrel is the leading antiplatelet drug in China, an ADP receptor inhibitor used to treat blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It has a dominant position (over 60% market share) of antiplatelet drugs with sales reaching $0.32B globally last year. It is mainly marketed by Sanofi-aventis under the brand name Plavix, with 5 other 5 domestic approved manufacturers including Shenzhen Salubris with Taijia (泰嘉). About 30 new entrants including Dr. Reddy's and Jiangsu Hengrui are seeking SFDA regulatory approvals. The drug should continue with a favorable growth trend going forward. Ozagrel, a thromboxane A2 inhibitor, is the second best selling antiplatelet drug in China. The ozagrel market is also growing rapidly, but highly competitive with various doses and formulations provided by about 104 approved companies and 40 potential entrants in China. Ligustrazine, another antiplatelet drug, has a similar competitive landscape as ozagrel, with about 164 approved or potential domestic players.

 

(3)Thrombolytic drugs include a series of enzymes that activate plasminogen to effectively degrade fibrin clots, different from anticoagulants and antiplatelet drugs which decrease the progress of the clotting. Drugs in this area, including streptokinase, urokinase, and recombinant tissue plasminogen activator (rtPA), have a low single digit market share but also a promising future. Please find more information about Chinese thrombolytic drugs in cover story of Volume 43 of the China Pharmaceutical & Biotechnology Review.