Let'S See Through The Clouds: Homemade Bio Similar Drugs Are On The Market.

In July 7th, the listing review of trastuzumab biological analogues submitted by Fu Hong Lin has left the CDE's review queue, and is expected to be approved in the near future to become the first domestic trastuzumab analogues.

A week ago, in June 30th, Fu Hung Han Lin announced that HLX02 (Trastuzumab Injection)'s first EU order product was finally tested and packed before its Xuhui production base was successfully completed, and officially embarked on its journey to Europe.

Since the first biological similar drug rituximab was launched in early 2019, many biopharmaceuticals have been listed in China, including the aladuximab, An Jianning, the bezavin monoclonal antibody (An Ke) of Qilu pharmaceutical, and bevacizumab, which was approved to be listed in June 19th.

Since June 2018, 16 domestic biologically similar drugs have been submitted to the market. After the first domestic biosimilar drug, 5 products were developed and declared according to the biological analogues. Fierce competition is inevitable. Domestic enterprises face many challenges and opportunities in R & D, variety selection, card listing and subsequent commercial sales, channels, capacity and price.

Following the United States and Europe, the Chinese market has become the most popular research and development pipeline for biosimilar drugs in terms of the layout of PD-1/L1 drugs. It is expected that in the next ten years, bio pharmaceutical products will face greater market opportunities if the biological products of the global pharmaceutical industry are facing patent expiration.

step by step one goes as far as a thousand li

Biopharmaceuticals refer to therapeutic biological products that are similar in quality, safety and efficacy to those approved for reference. One of the major advantages of biopharmaceutical drugs is price when it is as safe and effective as the original biopharmaceuticals.

Unlike the imitation of small molecule chemicals, the development of biological analogues is much more complicated. Because of the characteristics of the manufacturing process and the molecule itself, it is very difficult for the biological macromolecule drugs to be the same as the structure and function of the original drug. The European Union, the United States, China and WHO gave the definition of biological analogues respectively. Although the descriptions were not identical, they all emphasized the three important aspects of biological analogues: quality, safety and effectiveness.

According to the guidelines issued by the former State Food and Drug Administration (CFDA) in 2015, "with the development of biotech patents and the development of biotechnology, the research and development of bio analogues based on the quality, safety and efficacy of the original biological drugs will help improve the accessibility and reduce the price of biological drugs and meet the needs of the masses."

Among them, the general idea of R & D of biological analogues is based on the comparability test, which is based on the similarity of reference drugs and supports its safety, effectiveness and quality control. Pharmaceutical, non clinical and clinical comparative trials should be carried out step by step in a progressive way.

With the development of biosimilar drugs in China, biosimilar drugs have been approved in July 2019, and many biological products have been declared according to biological analogues.

According to data from Liu Shigao, co-founder and chief executive officer of Fu Xing Han Lin, who had been at the International Conference on rituximab, the original biopharmaceuticals should undergo discovery / screening, analysis of science, animal experiments, and 1, 2, 3 and 4 clinical trials, which will take about 8~10 years and $800 million. Biological analogues need to undergo Analytical Science (head to head), animal experiments (head to head), bioequivalence (head to head), clinical PK/PD (head to head), clinical efficacy, safety (head to head) and phase 4 clinical trials and other steps, which cost about 7~8 years, 1~3 billion.

With ten thousand years of domestic medicine, domestic organisms have gradually entered the harvest period. But in catching up with international speed, the speed of biological analogues is far less than that of small molecule drugs. Liu Shigao said, "Han Li Kang (general name: Rituximab Injection) is the world's third approved biosimilar drug rituximab." In February 2017, South Korea's Celltrion Truxima was first approved by the European Union. In June 2017, Sanders's Rixathon was approved in the European Union. In November 2018, Truxima was also approved by the FDA.

Song Ruilin, President of the China pharmaceutical innovation promotion association, said: "in the field of small molecule drugs, we have nearly twenty years' gap with Europe and the United States, but the development of biologically similar drugs is now only three to four years away."

Explore and expand

IQVIA, the international medical consultancy, predicts that with the expiration of the patents on biological drugs and the listing of a large number of biopharmaceutical drugs, the global bio analogues will reach the market scale of about 30 billion dollars in 2020. The market share of China's biopharmaceutical and biological analogues accounts for about 1% of the world's total. The number of research projects in the world ranks first in the world, and is concentrated in the field of cancer and immune diseases. It is estimated that by 2030, the sales of Chinese antibody analogues will reach US $4 billion 200 million, accounting for 35% of the total sales of these drugs.

The research and development layout of biosimilar drugs in domestic pharmaceutical enterprises is concentrated on the "famous varieties" such as adalimumab, bevacizumab, rituximab, trastuzumab and so on. In June, the application of adalimumab submitted by Zhengda Tian Qing was accepted by CDE and became the sixth domestic company to submit Miller bio similar drugs. Others include Fu Hong Lin, XinDa bio, Corelle Jerry, Shenzhou cell, Hai Zheng pharmaceutical, Qilu pharmaceutical, Li Zhu pharmaceutical, Sansheng Guo Jian, Shuang Lu pharmaceutical, Hua Lan gene and a large number of enterprises.

In 2019, sales of the 4 best selling drugs, including adalimumab, bevacizumab, rituximab and trastuzumab, amounted to $38 billion 760 million, down 4.3% from the same period. The total sales volume of these four drugs in China is nearly 5 billion yuan, up nearly 40% over the same period last year.

The advantage of bio analogues is price, and the price competition is directly related to the original research and similar products.

From the experience of European and American markets, the first biological advantage of similar drugs is obvious. According to IMS data, the bioequivalent of the first listed biotech market in the European market is very fast, and the share of all biosimilar drugs market is relatively high after the stabilization (averaging 70%). The competition is smaller, and the price decline is obvious compared with the original research drug, which is the main reason to help the first listed bio similar drug to seize the market quickly.

After the listing, Han Li Kang further lowered the price. The price at the time of listing is 1648 yuan /10ml:0.1g, which is lower than about 30% of the original Roche drugs with the same quality regulations, and the price is reduced by about 30%. In the later stage, the price is reduced to 1398 yuan / 100mg (10ml /).

In March 23, 2020, Fu Hung Han Lin released the 2019 annual report, the first domestic biological analogues drying out the first year's report card. In 2019, the revenue of Fu Hong Lin was about 90 million 900 thousand yuan, and its main contribution came from the commercialization of rituximab. The sale of rituximab in China is responsible for Fuxing medicine, which is divided into sales net profit, selling for 7 months, the total sales volume is about 190 million yuan, and the sales revenue of Fu Hong Lin is 79 million yuan.

"The listing of Han Li Kang has opened the era of China's new antibody drug. Market feedback, the product is currently in short supply, constrained by capacity, at present, enterprises are already expanding their efforts. " An industry insider told the economic report twenty-first Century, "the product is currently applying for new indications, and the application for listing in the US and the EU will become the first bio similar product to produce global sales in China, and the market potential is worth looking at."

At the same time, the original pharmaceutical companies adopted a more direct way of competition. Since 2017, many popular McAb drugs have entered the health insurance directory through a substantial price cut. Rituximab, the original research drug, is Roche's rituximab. It is the first monoclonal antibody designed for the treatment of cancer by the Roche gene, FDA. Currently, rituximab already has biosimilar drugs in Europe and the United States. In April 21, 2000, Roche rituximab was approved by CFDA and entered the health insurance directory through negotiation in 2017. The price dropped by 58.45%. Thereafter, the market was clear. The size of the 500mg/50ml/ bottle is reduced from 16041 yuan to 8298 yuan, and the 100mg/10ml/ bottle size is reduced to 2418 yuan.

In November 2019, the national health insurance access negotiations were settled, and seven years after the reelection of Miller (adalimumab), the global "medicine king" has entered the medical insurance for many years. Xiu Mei Lecong single price more than 7600 yuan, to the net to take the initiative to price 60% to 3160 yuan, until the 1290 yuan / branch won the national health insurance directory.

Under such circumstances, enterprises with biological analogues have to adjust their strategies to compete with the original ones at lower prices.

"The industry as a whole still has a lot of upward space. There is a substitution process for the domestic similar drugs, or some market space can be grabbed." Qu Rong, general manager of the Oriental high Saint Shenzhen company, told the economic report in twenty-first Century, "but when the price of the original drug is reduced to 60%-70%, the value and income of the similar pharmaceutical enterprises may not be as high as before, and it is also not consistent with the financial model during the establishment period."

Zhang Wenjie, President of Fu Hong Han Lin, said: "the market of bio similar drugs will not become red sea. The difficulty of biological analogues is very high, and not every company can do it. Even through the three phase of clinical practice, it is not so easy to invest in production facilities, production quality control and production cost competitiveness.

In addition to the domestic market, China's bio similar enterprises may also fight overseas.