If the fight against the new crown virus is an encounter, then hardening the hepatitis B virus for more than 30 years is another epic protracted battle that the Chinese have experienced.
In the 1970s and the end of the 1980s, two large-scale hepatitis B virus outbreaks made China a "hepatitis B power". At the peak of 1992, there were 120 million hepatitis B virus carriers, which even accounted for more than 30% of the total number of carriers worldwide in the same period.
The vision of "ten people and one hepatitis B" is far greater and more profound than the spread of the new crown virus on the entire Chinese society today. "China's first disease" is like a lingering nightmare, affecting the growth of generations.
In 2020, there will be two related topics about hepatitis B disease: "72 million hepatitis B virus carriers in my country" and "China removes the hepatitis B status as a big country" on the hot news. But at this time, the Chinese people's response to the hepatitis B virus has been calm and calm, and the consternation and panic that were once gradually dissipated.
This is not because of being covered up by the clamor of the new crown epidemic, but because of the long confrontation with the hepatitis B virus, China has gradually worked out a set of effective prevention and treatment plans.
From "zero treatment rate" to the removal of the "hepatitis B power" hat, the grand battle against liver disease (the "epidemic") for more than 30 years is the historical mark that best expresses the growth and changes of Chinese pharmaceutical companies. The industry has gone from being weak and backward, knowing the shame and then courageously catching up, to today's timeline of becoming a strong country in pharmaceutical innovation.
In the late 1980s, China, which relied on foreign hepatitis B vaccine technology and imported medicines to prevent and treat hepatitis B virus, has now made considerable progress, regaining the fate of the Chinese people from the hepatitis virus:
The positive rate of hepatitis B surface antigen in the general population dropped from 9.75% in 1992 to 7.18% in 2006, and then to about 5% in 2020, and from high-endemic areas to moderate-endemic areas; the number of hepatitis B virus carriers decreased from 120 million in 1992 It has dropped to 93 million in 2006 and 72 million in 2020. The prevalence of hepatitis B has been declining year after year.
In 2016, among the top 10 global antiviral drugs, "Runzhong" became the only Chinese brand selected, which also achieved a historic breakthrough for Chinese pharmaceutical companies in the field of antiviral drug development.
The seemingly emergence of "Runzhong" is actually the result of the accumulated accumulation of the company behind it, Zhengda Tianqing, after decades. Since the launch of Qianglining, the first cooperatively developed liver disease drug in 1988, CP Tianqing has made the development of liver disease drugs its first choice in the pharmaceutical industry.
Today, Chia Tai Tianqing has become an absolute powerhouse in this field in China. It can even be said that CP Tianqing's 32-year battle for liver disease drug development is half the history of China's hepatitis virus struggle.
Hepatitis B power off the road
Fighting against hepatitis B virus and removing the title of "hepatitis B power", the price and hardship China has paid far exceeds most public perceptions.
"My hometown is a small village by the mountain and the sea. The mountains and the sea are the sea, but the mountains and the sea do not support people. The local residents have many liver disease patients, and some even the whole family is hepatitis B. A small part of it The unfortunate ones gradually develop into liver cirrhosis and liver cancer. The HBV virus brazenly dances with the joy of death spread by hepatitis B..."
In 2004, the female writer Zhao Yuhong described the living conditions of hepatitis B virus carriers in her novel "China's First Disease". There was such a description through the mouth of a college student hepatitis B carrier Ouyang Ziyan.
Although it is only a novel, the description of the plight of Chinese families caused by the hepatitis B virus is truly engraved in the minds of many people, especially in the "Trilogy of Hepatitis B, Cirrhosis, and Liver Cancer". Mass portrait.
"In order to treat the disease, they listened to the so-called expert guidance and propaganda in the advertisements. They took countless medicines and spent countless money. All kinds of liver medicines almost emptied the villagers’ pockets, but the condition did not improve. There are more and more patients like snowballing..."
But how many people know that in China, hepatitis B, which has caused poverty in countless families due to the virus, is also a virus that causes disease due to poverty.
From the 1970s to the end of the 1980s, the two major outbreaks of hepatitis B virus in China were indirectly caused by the backward economic development level. Hepatitis B was the "poor disease" of that era.
At the beginning, China’s public health system was almost impoverished and ignorant, coupled with a lack of awareness of hepatitis B. As a result of the shortage of medical equipment, syringes that were reused after simple sterilization and later the "plasma economy" of paid blood donation prevailed, causing large-scale cross-infection. , Weaving the "hepatitis B power" hat.
It was not until 1988 that China decided to introduce hepatitis B vaccine production technology as a breakthrough in the prevention of hepatitis B virus. In 1992, when Xiaoping made a speech during his southern tour, China did a large-scale seroepidemiological survey of hepatitis B prevention and control, so as to recognize the effect of hepatitis B. List of negative profits in Chinese society.
At that time, the survey results showed that the hepatitis B virus carrier rate (the positive rate of surface antigen) among people aged 1 to 29 in China was 9.75%, which was much higher than the 8% "high infection area" defined by the WHO.
It was not until 1997 that the "Blood Donation Law of the People's Republic of China" was revised and passed, and the chaos in the use of blood products was finally brought under control, and the largest breeding ground for the spread of hepatitis B virus was controlled.
However, the huge ethnic group of hepatitis B virus carriers with a population of more than 100 million is still like a heavy "cross" imprisoned on the backbone of the Chinese people, bringing an indescribable social and economic burden.
At that time, in patients with liver cirrhosis and liver cancer around the world, hepatitis B caused about 30%-45%, but in China, the proportion of data is as high as 60% and 80%. Not only the spread of the virus itself, but a series of socially sensitive issues such as hepatitis B discrimination have also affected the pace of China's economic catch-up.
Until 2002, the State Council formally approved the inclusion of hepatitis B vaccine in the scope of the national plan for immunization of children and vaccinated every newborn for free. So far, the whole of China, children groups have realized the prevention and protection of hepatitis B virus.
According to the health reform and development during the 13th Five-Year Plan, the infection rate of hepatitis B virus among children under 5 years of age in China has dropped to less than 1% in 2019, and the positive rate of hepatitis B surface antigen in the general population has also dropped from high-endemic areas to the level of middle-endemic areas. .
The "hepatitis B power" hat is finally "off the shelf." The people who once "talked about liver discoloration" finally ushered in the desired result for decades. However, the protracted battle against the hepatitis B virus is far from over.
"There are still more than 70 million (hepatitis B) virus carriers in China, and about 20-30 million need to be treated. Among the people in need of treatment, only 11% can be treated in a standardized way." Yang Xizhong, executive vice chairman of the China Hepatitis Prevention Foundation Called.
"Half" hepatitis struggle history
In the next ten years, to achieve the goal of completely eradicating viral hepatitis, China and Chinese pharmaceutical companies still have a long way to go.
After all, the population of China infected with hepatitis B virus accounts for nearly a quarter of the total patients in the world, and only about 4 million of them are undergoing antiviral treatment. Medication habits are still a pain point.
On the "World Hepatitis Day" on July 28, 2020, China put forward the theme of "active prevention, active testing, standardized treatment, and comprehensive curbing of hepatitis harm". After taking off the "hepatitis B power", the fight to eliminate viral hepatitis is already in the process.
In fact, at the same time when China opened a vaccine to prevent hepatitis B virus, Chinese pharmaceutical companies have already taken action in the development of drugs for the treatment of viral hepatitis.
In 1988, CP Tianqing launched the first cooperatively developed liver disease drug "Qianglining". In fact, it was the launch of this drug that opened the prelude for Chinese pharmaceutical companies to tackle the hepatitis virus. CP Tianqing has also gradually established a leading position in the field of domestic liver disease drug research and development and industrialization through a strategy of focusing on liver disease.
2016 can be described as a year when CP Tianqing had a big outbreak in the field of liver disease drugs. Its liver disease product Runzhong (Entecavir Dispersible Tablets) was selected as one of the top 10 antiviral drugs in the world, and won the "Most Clinical Alternative Value Generic Drug" in the second China Pharmaceutical Innovation Brand Selection.
Runzhong's core product not only quickly became the first-line drug for hepatitis B treatment in China, but also brought more than 3.5 billion yuan in sales revenue for CP Tianqing that year. At that time, CP Tianqing's liver disease medications had already accounted for 22.5% of the domestic hospital market, overwhelming many multinational pharmaceutical companies to rank first.
In the same year, CP Tianqing also licensed to Johnson & Johnson the right to develop an innovative hepatitis drug outside of China, and received a total of US$253 million in down payment and mileage, as well as a sales commission after the listing. The "internal strength" of Chinese pharmaceutical companies can also be seen.
Today, CP Tianqing has a series of chronic hepatitis B antiviral products such as Runzhong (Entecavir dispersible tablets), Qingzhong (tenofovir disoproxil fumarate tablets), Mingzheng (Adefovir dipivoxil capsules), etc. , A new generation of antiviral drug TAF is waiting to be approved for marketing, and a number of category 1.1 innovative drugs in the field of liver disease are entering clinical research one after another.
According to the statistics of Minai.com, the terminal sales of public hospitals in 2017 showed that CP Tianqing’s Entecavir Dispersible Tablets and Adefovir Dipivoxil Capsules accounted for 80% and 29% of the market share, both of which were the first.
In addition, CP Tianqing also provides treatment products such as Ganlixin, Tianqingganping, Tianqingganmei, etc. which can quickly inhibit inflammation for patients with hepatitis B and liver injury.
In 2019, Chia Tai Tianqing had sales of more than 24 billion yuan, of which liver disease drugs accounted for nearly a quarter, served more than 2,000 general hospitals and liver disease hospitals, and had gained up to 35% market share in the field of anti-hepatitis B virus drugs in China .
From the first liver drug Qianglining to the "explosive" product Runzhong, to now it has a rich liver disease drug product line, and it can launch a liver disease treatment drug in less than three years on average. CP Tianqing has developed liver disease drugs for 32 years. It can be said that "half of China's history of fighting against the hepatitis virus."
"Using liver disease drugs as an entry point has a broad market prospect, but considering the complexity of the pathogenic mechanism of hepatitis virus and the difficulty of elimination, this means that the development of liver disease drugs requires long-term persistence and continuous innovation."
Just as Wang Shanchun, President of CP Tianqing, said, for a country that still has a large number of people infected with hepatitis virus, innovative drugs are the true yardstick for testing the level of pharmaceutical companies.
After more than 30 years of accumulation, precipitation and innovative development of generic drugs, CP Tianqing’s development thinking has also shifted from "combination of imitation and innovation" to "combination of innovation and imitation". It is the Chinese medicine that continuously strengthens innovative drugs with independent intellectual property rights. The best solution to overcome the hepatitis virus.
Future test
According to the age structure of the Chinese population and the impact of the popularization of the vaccine, it is estimated that the number of HBsAg-positive people will continue to decline in the future, but the number of hepatitis B virus carriers in China will still be about 27 million in 2060.
Data from the research report of Ping An Securities in the field of liver disease medications shows that chronic hepatitis B will continue to be a major disease and a huge drug potential market in China for a long time to come.
| Data source: Ping An Securities
According to data from the China Infectious Disease Reporting System, 80%-90% of new patients with hepatitis B virus disease in China each year are chronic hepatitis B. And as mentioned above, among the 30 million or so domestic hepatitis B patients in need of treatment, 90% of chronic hepatitis B patients have not received treatment.
The main reason for the low treatment rate is that hepatitis B has no obvious symptoms of discomfort, patients have low compliance, and are unwilling to take long-term medication. If a breakthrough drug with a high cure rate for hepatitis B emerges, it will greatly increase the enthusiasm of patients in active treatment. Even if the penetration rate reaches about 10%, this will form a market size of about 150 billion yuan.
With the continuous expansion of innovative drugs, hepatitis B curative drugs will be the direction for Chinese pharmaceutical companies to make breakthroughs. At present, the hepatitis B drugs of various domestic companies are in the clinical stage and are seeking breakthrough treatments.
In addition, liver cancer is currently the fourth most common tumor in China. There are about 460,000 new liver cancer patients every year, and it is also the second most fatal tumor in China. The mortality rate is 26/100,000. The 5-year survival rate of liver cancer patients is only It was 12.5%, and 85% of the patients were in the middle or late stage when they were first diagnosed.
In fact, liver cancer caused by hepatitis B accounts for about 80% of liver cancer patients. If patients with chronic hepatitis B are not controlled, the annual incidence of liver cirrhosis is 2%-10%, and the annual probability of liver cancer in patients with liver cirrhosis is 3%-6%. The average survival time of patients with advanced liver cancer is less than 2 years.
| Source: Ping An Securities
Therefore, in addition to the treatment of chronic hepatitis B, early liver cancer screening and innovative drugs have also become the focus of domestic liver disease pharmaceutical companies.
On January 7, 2021, Chia Tai Tianqing and Genetron Health, a cancer precision medicine company, signed a strategic cooperation agreement. The two parties, based on liquid biopsy technology, are based on the early liver cancer screening product HCCscreen to jointly develop the early liver cancer screening market.
In the next three years, Genetron Health will provide product production and laboratory operation services for the cooperation; Chia Tai Tianqing will use its sales experience and the resources of liver disease drug hospitals covering the country to increase the penetration rate and penetration rate of HCCscreen in the field of early cancer screening in China. Penetration rate, serving people at high risk of liver cancer, including hepatitis B virus carriers and patients with other liver diseases.
In the field of liver cancer treatment, at the end of May 2020, Kangfang Bio-PD-1 mAb AK105 (Pianprizumab) was combined with the anti-tumor chemical agent Anlotinib independently developed by Chia Tai Tianqing to initiate phase III clinical trials. The goal is to treat first-line advanced hepatocellular carcinoma (HCC).
Although the promotion of a series of policies such as "4+7 volume procurement" has brought operational challenges to all pharmaceutical companies, for CP Tianqing, which focuses on the field of liver disease, on the one hand, it has continuously increased the depth of its product line Expansion to deal with policy risks similar to centralized procurement. On the other hand, with the development of Internet medical care, the retailing of prescription drugs has brought new opportunities.
Chia Tai Tianqing, which has superior brand prescription drugs such as Runzhong, still has sufficient market competitiveness. With its rising R&D investment and rich accumulation in the field of liver diseases, it is not impossible for breakthroughs to cure hepatitis viruses in the future.
Conclusion
Looking back, it started as a pharmaceutical factory in the First Division of the Jiangsu Production and Construction Corps in 1969, and developed the first liver disease drug in 1988, and now it has become the king of the domestic liver disease field, especially the development of chronic hepatitis B treatment drugs. The success of Zhengda Tianqing The rise is also a microcosm of the history of the Chinese people fighting against the hepatitis virus.
As far as the rise of Chinese pharmaceutical companies is concerned, whether it is imitation or innovation, Chinese pharmaceutical companies such as Chia Tai Tianqing have become more and more clear about their growth paths, and they are increasingly showing strong vitality in market competition. . I believe that in the future, Chinese pharmaceutical companies with innovation as the banner will further increase their market share.
Finally, a new crown epidemic superimposed on the rapid penetration of Internet medical care has had a deep impact on the public's health concepts and medication behavior. How to guide and standardize medication for different patients, provide personalized intelligent medication reminders, health checkup and other services are also new challenges for Chinese pharmaceutical companies to directly face the user side in the changing environment.