Low-molecular-weight heparin products are being upgraded, and we’ll closely watch as the market landscape evolves.

　　To date, cardiovascular and cerebrovascular diseases remain the leading cause of death worldwide. Currently, therapeutic drugs for stroke and myocardial infarction primarily fall into three major categories: antithrombotic, anticoagulant, and antiplatelet agents. The 2009 edition of the National Medical Insurance Catalog lists 19 chemical entities belonging to these three categories—antithrombotic, anticoagulant, and antiplatelet agents. Among them, heparin, low-molecular-weight heparin, rivaroxaban, warfarin, and thrombolytic agents are the main varieties used in clinical practice and play an irreplaceable and critical role.
　　Rigid market demand remains stable.
　　According to comprehensive data from the China Pharmaceutical Industry Information Center’s PDB, in 2015, the global market for anticoagulant and antithrombotic therapies—the seven major pharmaceutical markets—reached US$19.738 billion, representing a year-on-year increase of 6.88%. In the late 1970s, low-molecular-weight heparin, an antithrombotic and anticoagulant drug, was introduced into clinical practice. This product offers superior efficacy compared to conventional heparin, with fewer bleeding side effects, higher bioavailability, longer half-life, and excellent anticoagulant performance. As a result, it has come to occupy the majority share of the anticoagulant market.
　　In 2015, the global heparin market reached US$12.58 billion, representing an 11.10% increase over the previous year. Among this, the original research heparin market in the world’s seven major pharmaceutical markets accounted for one-quarter of the total. Enoxaparin from Sanofi and Sandoz, as well as dalteparin sodium from Pfizer, Eisai, Janssen, and GlaxoSmithKline (GSK), together captured the largest share.

　　Among antithrombotic and anticoagulant medications used in hospitals, heparin and low-molecular-weight heparin remain widely prescribed in China. These drugs work by reducing the concentration of coagulation factors, thereby lowering blood clotting tendency or hypercoagulability and preventing thrombus formation or halting its progression. As the clinical use of heparin-based drugs continues to expand, the market for heparin raw materials has also been steadily heating up year after year.
　　Among domestic heparin products, low-molecular-weight heparin calcium ranks first, accounting for 44.64%; followed by enoxaparin sodium, which accounts for 26.55%; while ordinary sodium heparin accounts for only 11.98%, and other types account for the remaining 16.83%.
　　According to data from the CFDA’s official website: In 2016, there were 63 domestic manufacturers of heparin, holding a total of 165 production licenses. Seven imported manufacturers held 40 production licenses. In 2015, there were 32 competing manufacturers of heparin-related products in hospitals, including four foreign-invested companies—Sanofi, GlaxoSmithKline, Pfizer, and Alfa Wassermann—and 28 domestic manufacturers.
　　The top 10 vendors in terms of sales at public hospitals remain Sanofi, GlaxoSmithKline, Changshan Biochemical, Anhui Zhaokew, Pfizer, Alphapharm, Changzhou Qianhong, Qilu, Hangzhou Jiuyuan, and Wanbang Biochemical. Among these, foreign-funded companies account for 51.76% of low-molecular-weight heparin sales, while domestic companies account for 48.24%, resulting in a roughly even split. The top 10 vendors collectively hold 88.47% of the market, while the remaining 22 companies together account for the remaining 11.53%.

　　In the domestic low-molecular-weight heparin calcium market, GlaxoSmithKline’s Fragmin was launched in 1985 for hemodialysis indications, expanded to include perioperative thromboprophylaxis in 1987, and entered the coronary syndrome market in 1998. Fragmin was officially registered in China in 1992 and first launched on the market in 1995. For a long time, Fragmin maintained a high-growth trajectory; however, following the GSK incident, its sales in the Chinese market declined in 2014 and remained sluggish throughout 2015. This created development opportunities for domestic low-molecular-weight heparin calcium products. From 2013 to 2015, these products experienced sustained growth, with annual growth rates of 24.71%, 30.85%, and 15.59%, respectively. It is estimated that hospital drug consumption in China has now exceeded 1 billion yuan.
　　In 2015, GlaxoSmithKline’s Xuebilin accounted for 35.45%, a year-on-year decrease of 11.31%. As a result, domestically produced low-molecular-weight heparin calcium products showed rapid growth. Among them, Wanmaishu from Hebei Changshan Biochemical occupied 31.93%, while Limaiqing from Hefei Zhaokewas at 21.33%. The other four companies—Bopuqing from Tianjin Hongri, Unishu from Tongmeng Pharmaceutical, Saiboli from Shenzhen Saibaoer, and Tiantpuloning from Tianpu Biochemical—combined accounted for 11.29%.
　　Low-molecular-weight heparin sodium market
　　After the generic name of low-molecular-weight sodium heparin in China was redefined in 2010, the current market is composed of the following five brands: Sukeno from Jiangsu Wanbang, Jipailin from Hangzhou Jiuyuan Gene, Qizheng from Qilu Pharmaceutical, Xifquan from Italian Alfa Wassermann, and Sailuoxiping from Jilin Huakang. It is used to prevent blood clot formation during hemodialysis and can also be employed for the prevention of deep vein thrombosis.
　　Statistical data show that in 2015, the market for low-molecular-weight sodium heparin in hospitals in key Chinese cities reached 65.6 million yuan, representing a year-on-year increase of 19.14%. Among these sales, injectable solutions accounted for 88.11%, while powder-for-injection preparations made up 11.89%. Sukeno from Jiangsu Wanbang is a rapidly growing product in this segment.
　　Enoxaparin Sodium
　　With advances in science and the improved management capabilities of China’s CFDA, the country has accelerated its alignment with international generic drug names. In 2010, the CFDA changed Sanofi’s generic name for “Kexi” from “Low Molecular Weight Heparin Sodium” to “Enoxaparin Sodium.”
　　Sodium enoxaparin was approved for marketing by Sanofi-Aventis in 1993 under the brand name Clexane (Levonox). In 2009, the global market reached its peak at US$4.24 billion. After the patent expired in 2010, Sandoz’s generic version was approved, leading to a decline in the U.S. market. Emerging markets remain the primary source of growth for Clexane. In 2015, the global market stood at US$1.907 billion, making it still the world’s leading heparin-based drug.
　　In 2003, Sanofi-Aventis’ enoxaparin sodium was imported into China. In 2006, Hangzhou Jiuyuan Genetic Engineering launched a generic version of the drug. Currently, Shenzhen Tiandao Pharmaceutical and Hangzhou Jiuyuan Genetic Engineering are the main manufacturers in China. After 2014, Nanjing Jianyou and Suzhou Er Ye were approved, and in 2015, Chengdu Baiyu and Changzhou Qianhong were also approved. Now, there are six domestic manufacturers producing the formulation.
　　Statistical data show that in 2015, the market for enoxaparin sodium in hospitals in key Chinese cities reached 180 million yuan, representing a year-on-year increase of 17.64%. After experiencing volatile fluctuations from 2008 to 2012, the market has entered a growth trajectory. In 2015, Sanofi-Aventis held a market share of 93.02%, Hangzhou Jiuyuan Gene accounted for 6.66%, and Nanjing Jianyou took up 0.32%. It is expected that the market landscape will change in 2016, giving rise to a new competitive dynamic.

　　Dalteparin Sodium
　　Dalteparin sodium is a low-molecular-weight heparin sodium product manufactured by Pfizer in the United States, marketed under the brand name Fragmin. It is used to prevent blood clotting during extracorporeal circulation in hemodialysis or hemofiltration and to reduce the risk of thrombosis. Compared with conventional low-molecular-weight heparin sodium, dalteparin sodium has a lower weight-average molecular weight. It is primarily indicated for the treatment of conditions such as acute deep vein thrombosis, acute renal failure, unstable coronary artery disease, and surgery-related thrombosis. This drug boasts a longer half-life and is safer and more effective. In 2015, the dalteparin sodium market in key hospitals across China’s major cities reached 40.03 million yuan, representing a year-on-year increase of 28.13%.
　　In May 2014, the CFDA first approved domestically produced sodium dalteparin, with Hebei Changshan receiving the production license. In February 2015, Nanjing Jianyou was approved, and in February 2015, Changzhou Qianhong was also approved for production. By March 2016, three domestic companies would compete with Pfizer for the sodium dalteparin market, signaling a shift in the competitive landscape.
　　Nadroparin calcium
　　Bemiparin sodium, manufactured by Laboratorios Farmacéuticos in Spain, entered the Chinese market in 2014 under the trade name “Hibor.” As of 2015, no statistical data were available. In 2015, Nanjing Jianyou and Yantai Dongcheng Pharmaceutical obtained manufacturing licenses for nadroparin calcium. In 2016, Tianjin Biochemical Pharmaceutical and Hebei Changshan Biochemical Pharmaceutical also received manufacturing licenses. In 2015, only Nanjing Jianyou reported some sales volume.
　　Low-molecular-weight heparin (LMWH) and its formulations, now available in the domestic market, have replaced heparin in 80% of the clinical market. LMWH boasts enhanced anti-factor Xa and anti-factor IIa activities, a favorable ratio between these two effects, and multiple mechanisms of action, resulting in improved safety and reduced incidence of bleeding. Moreover, LMWH exhibits high bioavailability and a prolonged half-life, allowing for predictable anticoagulant effects and minimizing the occurrence of heparin-induced thrombocytopenia. As LMWH products continue to evolve and undergo further upgrades, they will increasingly align with international standards, and conventional low-molecular-weight heparin preparations are likely to face significant challenges in the future.
　　(This article reflects the author’s personal views only.)
　　About the Author: Cai Deshan is a contributing writer for Pharmaceutical Geography. He is a senior engineer and a seasoned researcher specializing in pharmaceutical market information. Currently, he serves as a senior advisor at Beijing Jialin Pharmaceutical Co., Ltd. He has 45 years of experience in managing enterprises within the chemical pharmaceutical industry. Copyright of this article belongs to Pharmaceutical Geography. Republishing is welcome, provided that the source and author are properly credited.
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