For the first time, heparin was incorporated into the country, which ushered in a change in the ten-billion market

Recently, Shanghai Sunshine Pharmaceutical Purchasing website published the "Notice on Filling in the Information of the Eighth Batch of State-Organized Centralized Drug Purchase". Starting from February 20, 2023, the joint purchasing Office will fill in the information of the eighth batch of State-organized centralized drug Purchase.

According to the notice, 41 varieties and 181 types of drugs are involved in the purchase. It is worth noting that heparin products have been included in national procurement for the first time, ushering in changes in the antithrombotic drug market.

Public data show that in 2021, the sales volume of terminal heparin and low molecular weight heparin preparations in China's public medical institutions exceeded 12 billion yuan, with a year-on-year growth of 12.98%. The sales of enoxaparin and Nardrin, which are included in the collection, are estimated to be 2.8 billion yuan and 2.7 billion yuan respectively in 2021.

Heparin "family" introduction

In 1916, Jay McLean, a Johns Hopkins medical student, was studying clotting substances when he accidentally discovered an anticoagulant in dog livers that Professor William Howell named "heparin."

After more than 100 years of development, the heparin "family" is now divided into common heparin (UFH), low molecular weight heparin (LMWH), heparin derivatives (e.g. Sulfonda hedecin sodium), and heparin analogs (e.g. Danaheparin).

Heparin is a compound of glucosaminoglycan (GAGs), which is a mucopolysaccharide sulfate alternately composed of D-glucosamine, L-iduronic acid and D-glucuronic acid.

Short chain preparation - low molecular weight heparin can be obtained by separation or degradation of ordinary heparin.

The production process of heparin is shown in the figure below. First, solid heparin crude is extracted from the small intestine mucosa of healthy pigs and then further processed, purified and refined to obtain heparin bulk. Heparin apis can be processed into standard heparin preparations or further depolymerized to obtain low molecular weight heparin apis and then prepared into low molecular weight heparin preparations.

Although the raw material of heparin is derived from pig intestines mucosa, the products produced vary greatly depending on the production process. For example, there are three major types of low molecular weight heparin listed in our country, such as da heparin, enoxaparin and nardrin, and some do not distinguish specific molecular weight unified name "low molecular weight heparin".

Ten billion heparin market, domestic replacement accelerated

Thrombosis is a cause or complication of many diseases, including atherosclerosis, cerebrovascular disease, coronary heart disease, pulmonary thromboembolism, and deep vein embolism after surgery or trauma.

In recent years, with the aging of the global population, the rapid increase in the number of cases diagnosed with venous thromboembolism (VTE) and the need for the prevention and treatment of COVID-19, the demand for antithrombotic drugs has shown an obvious increasing trend. Data show that in 2021, China's public medical institutions terminal (including China's urban public hospitals, county-level public hospitals, urban community centers and township health centers) antithrombotic drugs increased by 5.80% year-on-year, with a market scale of more than 30 billion yuan.

Antithrombotic drugs commonly used in clinic can be divided into three categories: antiplatelet drugs, anticoagulant drugs and thrombolytic drugs. Although new oral anticoagulant drugs such as dabigatronate and apoxaban have been emerging in recent years, heparin and low molecular weight heparin are still one of the most commonly used anticoagulant drugs in clinic.

Among the seven batches of chemical drug collection previously carried out, 9 antithrombotic drugs have been included in the national collection, including Apoxaban tablets, Rivaroxaban tablets, Clopidogrel bisulfate tablets, Dabigatranate capsules, ticagrelor tablets, bivarudine for injection, suldatandecyl sodium injection, etifibatide injection, tirofiban hydrochloride sodium chloride injection.

However, the large varieties of low molecular weight heparin, which ranks the first place in the market of antithrombotic drugs, have finally been officially included in the eighth batch of collection, including the two major varieties Enoxaparin and Nardrin. The market of antithrombotic drugs over 30 billion yuan will usher in a new round of changes.

Sanofi and Aspen have long dominated the enoxaparin and Nardrin markets, respectively, by virtue of their brands. However, in recent years, domestic pharmaceutical enterprises began to enter the heparin market, and the strength of Hepalrui, Jianyou Shares, Dongcheng Pharmaceutical, Changshan Pharmaceutical and Qianhong Pharmaceutical cannot be underestimated. China's postharvest domestic generic drug enterprises are expected to expand market share and accelerate the realization of domestic replacement of low molecular weight heparin.

Enoxaparin

Enoxaparin is one of the three types of low molecular weight heparin products with the largest market size and most indications. The original research enterprise is Sanofi, and 10 domestic enterprises have passed the consistency evaluation, including Suzhou Erye Pharmaceutical, Chenxin Pharmaceutical, Dongying Tiandong Pharmaceutical, Hebei Changshan Bio-chemical Pharmaceutical, New Era Pharmaceutical, Nanjing Jianyou Bio-chemical Pharmaceutical, Hongri Pharmaceutical, Changzhou Qianhong Bio-chemical Pharmaceutical, Shenzhen Tiandao Pharmaceutical, Hangzhou Jiuyuan gene.

In the first half of 2022, the sales volume of enoxafin in sample hospitals in China reached 1.187 billion yuan, with Sanofi occupying the largest market share of 45.3%. Followed by Shenzhen Tiandao Pharmaceutical, Nanjing Jianyou Shares, Hangzhou Jiuyuan gene and other domestic pharmaceutical companies.

Nardrheparin (Nartriheparin)

Nardrheparin is the second largest low molecular weight heparin in the market, slightly behind Enoxaparin, which was originally developed by Aspen. Nardrheparin has two preparations in China: Nardrheparin calcium injection and Nardrheparin calcium injection. Only Yantai Dongcheng passed the consistency evaluation for Nardrheparin calcium injection, while five enterprises passed the consistency evaluation for Nardrheparin calcium injection, namely Hongri Pharmaceutical, Hebei Changshan Biochemical Pharmaceutical, Zhaoke Pharmaceutical, Yantai Dongcheng North Pharmaceutical and Nanjing Jianyou Shares.

According to the data of Yaozhi, in the first half of 2022, the sales volume of Nardrheparin in sample hospitals in China was 895 million yuan, and the market share of Yuanyan APSEN was about 30%. Followed by Yantai Dongcheng Pharmaceutical, Nanjing Jianyou Shares, Hebei Changshan Pharmaceutical and other domestic pharmaceutical companies.

At present, the supply of heparin is affected by the quantity of raw material pigs, and the room for production growth is limited.

But as a classic anticoagulant drug, it has a very stable base demand. In addition, with the clinical promotion of low molecular weight heparin in postoperative venous thrombosis prevention and acute coronary syndrome, as well as anti-tumor adjuvant therapy, the demand for heparin will continue to increase in the future.

This time, the country has included low molecular weight heparin in the procurement list, which is expected to further improve the availability of drugs and benefit more domestic patients.

For enterprises, the country is undoubtedly the most effective means to quickly increase the volume in the terminal and seize the market. On the heparin track, imitation enterprises such as Hepalink, Jianyou Shares, Changshan Pharmaceutical, Dongcheng Pharmaceutical and Qianhong Pharmaceutical are expected to seize the market quickly through Guocai and form a new market competition pattern.

However, post-harvest price reduction is an inevitable trend, which requires striving to realize the integration of heparin apis and preparations, and actively participating in domestic competition. Meanwhile, enterprises should try their best to expand foreign markets.