Insulin national procurement is approaching Ganli, Tonghua Dongbao, and the Federation can take the opportunity to win back the game?

Before the end of 2021, insulin, which has a history of one hundred years, is about to usher in a new historical turning point in the Chinese market
.
According to news from the Shanghai Sunshine Pharmaceutical Purchasing Network, the sixth batch of the national drug centralized procurement of insulin special work will be opened in Shanghai on November 26
.
The medicines collected this time include prandial human insulin, basal human insulin, premixed human insulin, prandial insulin analogues, basal insulin analogues, and premixed insulin analogues, with a total of 6 purchase groups
.
Enterprises in each procurement group that meet the qualifications for declaration shall declare according to the quotation unit, and there are a total of 11 quotation units
.
The overall reported volume is 214 million, of which 90 million second-generation insulins and 124 million third-generation insulins
.
From the perspective of the number of product specifications included by each company, Novo Nordisk has the most product specifications (19), followed by Eli Lilly (13), and Tonghua Dongbao and Zhuhai Federation also have 10 product specifications included
.
The quotation units of each purchasing group for the centralized insulin procurement are represented by the specifications of 3ml: 300 units (refills).
Among them, the highest effective declaration price for mealtime, basic, and pre-mixed human insulin is 50 yuan/piece; mealtime, pre-mixed insulin The highest effective declaration price of mixed insulin analogues is 72 yuan/piece; the highest effective declaration price of basal insulin analogues is the highest, which is 132 yuan/piece
.
Companies that have obtained valid domestic registration approvals before November 14 this year (inclusive) can participate in this special collection of insulin
.
International insulin giants Novo Nordisk, Eli Lilly, Sanofi and China's leading insulin companies Tonghua Dongbao, Tianmai Bio, Ganli Pharmaceutical, Zhuhai United Laboratories, Yuheng Pharmaceutical, Wanbang Biochemical and Dongyang Sun will compete on the same stage
.
This will also greatly improve the patient accessibility of insulin in the Chinese market and open a new chapter in the historical development of China's insulin
.
The research and development of insulin used to be China's closest field to global innovation
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In the early days of the founding of New China, Chinese researchers overcame various difficulties to artificially synthesize bovine insulin, leading the world
.
However, in the past century, the leaders in promoting the advancement of insulin technology are still multinational pharmaceutical companies represented by Novo Nordisk, Eli Lilly and Sanofi, and these three pharmaceutical companies have long occupied most of the Chinese insulin market
.
It remains to be seen whether China's insulin market can change the existing pattern through this special collection
.
The efforts of Chinese researchers The history of Chinese people's use of insulin is almost synchronized with the world
.
According to literature records, cases of insulin treatment were recorded in Peking Union Medical College in 1923
.
However, it was not until the founding of the People's Republic of China that Chinese researchers really participated in the research and development of insulin, and left a strong mark in the history of the world's insulin development
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In 1955, the British chemist Sanger completed all the sequencing of insulin, making insulin the only protein whose chemical structure was elucidated at that time
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Based on this work, Sanger won the Nobel Prize in Chemistry in 1958
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Sanger's work laid the foundation for synthetic insulin
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However, the mainstream view in the academic circles at that time was that once the disulfide bonds of insulin are disassembled, it is impossible to restore its biological activity.
This also means that artificially synthesizing insulin is remote or impossible
.
However, a group of Chinese researchers began to move towards "synthetic insulin
.
" In 1959, artificial fully synthetic insulin was awarded the code name "601" of the State Secret Research Project
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This number means that this was the number one mission in the 1960s
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At that time, the economy of New China was in the most difficult period.
China's biochemical research foundation was extremely weak.
Not only was there a shortage of talents, but many related scientific research equipment were almost completely blank
.
Synthetic insulin requires a large amount of various amino acids and biochemical reagents, which are not only unavailable domestically, but also difficult to purchase overseas, and are expensive
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Faced with many difficulties, the main institution participating in this research and development, the Institute of Biochemistry (Institute of Biochemistry) of the Chinese Academy of Sciences, began to self-reliant.

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The scientific research personnel draw the pictures and design the necessary equipment for the experiment, and leave it to the factory to do it
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In response to the supply problems of various amino acids and related reagents, the Institute of Biochemistry established the "Dongfeng Biochemical Reagent Factory", which specializes in the production of various amino acids and various necessary chemical reagents, which not only provides "raw materials" for the synthesis of insulin, but also completes the whole process.
The development of biochemical research in China has provided basic support
.
It was under these conditions that on September 17, 1965, China was ahead of all countries in the world and synthesized bovine insulin
.
Tislius, director of the Institute of Biochemistry at Uppsala University in Sweden, Nobel Prize winner and Chairman of the Nobel Prize Committee, once commented: "The United States, Switzerland and other countries with experience in peptide cooperation failed to synthesize it ( Insulin), dare not to synthesize it
.
You do not have the expertise and experience in this area, but you have synthesized it, and you are the number one in the world, which surprised me
.
” Although at present, this method of artificially synthesizing bovine insulin is already very good.
Less adopted
.
However, as the world's first fully artificially developed protein, this is a breakthrough in the field of Chinese drug research and development.
Its achievements are comparable to the atomic bomb that was just successfully tested at that time.
It declared the strength of China's scientific research to the world and greatly inspired China.
Research staff
.
This kind of "insulin spirit" of Chinese scientific and technological workers who have dared to make breakthroughs, are good at studying, and have a big picture in mind in particularly difficult times has also been passed down to this day
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The rise of local insulin From the use of insulin products by Chinese people to the independent research and development of insulin by Chinese local companies, it has spanned 75 years.
In other words, the history of local insulin production in China has only been more than 20 years
.
China's local insulin is closely following the trend of the world from the second generation of insulin
.
In 1995, in the early stage of reform and opening up, one of the country’s large-scale publicly sent overseas students, Gan Zhongru, after 13 years of studying and working in the United States, officially returned to China to study recombinant human insulin together with his Peking University classmate Li Yikui
.
Li Yikui is the chairman of Tonghua Dongbao
.
In June 1998, Ganli Biologics, the predecessor of Ganli Pharmaceutical, was established in Beijing
.
Soon after the establishment of the company, Gan Zhongru and his team developed China's first biosynthetic human insulin injection and sold the patent to Tonghua Dongbao
.
Subsequently, Tonghua Dongbao named it Gan Shulin and went public
.
At that time, only Eli Lilly and Novo Nordisk had the same products.
Sanofi's similar products were not yet on the market.
This made China the third country in the world that could produce and sell recombinant human insulin
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Tonghua Dongbao thus established its position as the second-generation insulin leader in China
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In January 2005, in order to solve the capital bottleneck and demand for production capacity faced in the development process, Ganli Pharmaceutical introduced Tonghua Dongbao as the controlling shareholder of Ganli Pharmaceutical, the latter holding 41.
50% of the equity of Ganli Pharmaceutical
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So far, the Chinese insulin giant has begun a complicated history of entanglement
.
In October 2005, the third-generation insulin of Ganli Pharmaceutical, the recombinant insulin glargine "Chang Xiulin" was born, and the patent was held by Ganli Pharmaceutical
.
In terms of product distribution, Tonghua Dongbao sells second-generation insulin, and subsidiary Ganli Pharmaceutical is responsible for the third-generation R&D and sales
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For Ganli Pharmaceutical, although there are new products on the market, there are many shortcomings in capital and experience.
Its third-generation insulin has been on the market for three years, but the company is still in a state of loss
.
It was not until March 2010 that Ganli Pharmaceuticals introduced strategic investor Qiming Venture Capital (with Minghua Innovation as the main body) and obtained 70 million yuan equivalent in US dollars in cash
.
The addition of Qiming Venture Capital also diluted Tonghua Dongbao's equity share to 29.
43%, and since then, Ganli Pharmaceutical has opened the road of independent development
.
It was not until July 2011 and September 2012 that Tonghua Dongbao and Dongbao Group successively transferred all their equity interests in Ganli Pharmaceutical, and the two parties formally "separated"
.
After that, Ganli Pharmaceutical hit the IPO three times in the A-share capital market, and did not succeed in listing until 2020
.
The Chinese market has changed so far, Ganli Pharmaceutical is still the main supplier of local third-generation insulin
.
In 2020, Chang Xiulin's terminal sales in public medical institutions in China was 2.
559 billion yuan, an increase of 15.
46% year-on-year, and it accounted for more than one-third of the domestic insulin glargine injection market share
.
Gan Li Pharmaceutical has used recombinant insulin lispro (fast-acting), recombinant insulin glargine (long-acting), insulin aspart and protamine zinc, recombinant insulin lispro (25R), insulin aspart 30 and protamine human insulin mixed (30R), etc.
With 6 products, it has become a leading company in the domestic insulin industry
.
As its main competitor, in 2020, Tonghua Dongbao’s income from human insulin will reach 2.
207 billion yuan, accounting for about 80% of its total revenue; the income from the third-generation insulin, namely insulin glargine, is only 131 million yuan, accounting for less than 5 %
.
According to Tonghua Dongbao's 2021 semi-annual report, it currently has 3 varieties of insulin aspart injection, insulin aspart 30 injection, and insulin aspart 50 injection
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Among them, insulin aspart injection has completed the production and development site inspection and drug GMP compliance inspection in May this year, and insulin aspart 30 injection and insulin aspart 50 injection were submitted to NDA registration data in June this year
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With the development of Ganli Pharmaceutical and Tonghua Dongbao, more and more domestic insulin companies have joined
.
In the national special collection of insulin, a total of 81 second- and third-generation insulin products are involved.
Local companies include Ganli Pharmaceutical, Tonghua Dongbao, United Laboratories, Jiangsu Wanbang, Hefei Tianmai, and Dongyang Sun Pharmaceutical
.
In the fiercely competitive second-generation insulin market, in addition to Ganli Pharmaceutical and Tonghua Dongbao, Dongyang Sun Pharmaceutical, Yuheng Pharmaceutical, Federal Pharmaceutical, Jiangsu Wanbang, and Hefei Tianmai also have related products approved for listing
.
As the “leader” of the local second-generation insulin, Tonghua Dongbao has 5 second-generation insulin products with 8 specifications included in the centralized procurement
.
So after the special collection, whether Tonghua Dongbao can continue to maintain the leading position of second-generation insulin is still full of uncertainties
.
While local Chinese companies are still in the process of launching three generations of insulin products one after another, there is still a lot of room for the third generation of insulin market
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Among the current domestic third-generation insulin players, the third-generation insulin glargine from Ganli Pharmaceutical and United Laboratories was launched a little earlier, and the third-generation insulin from Tonghua Dongbao, Hisun Pharmaceutical and Dongyang Pharmaceutical were all launched soon
.
Novo Nordisk, a multinational company, has an absolute advantage in the three-generation insulin products of Aspart, Degu and Dite
.
In 2020, Novo Nordisk's financial report shows that its sales of insulin aspart in China reached 2.
075 billion Danish kroner (approximately 2.
132 billion yuan); while Degu and Dete insulin, only Novo Nordisk is currently listed in China
.
For many years, local famous insulin production companies have been intensively working in second- and third-tier cities
.
The main domestic island market is still controlled by multinational giants
.
Local companies all hope to use their own price advantages to change the market competition and realize the domestic substitution of insulin through this national special collection of insulin
.
Where is the insulin heading? Despite the 100 years of development and the technological innovation of the third generation of insulin, insulin has become an important product for the treatment of diabetes
.
However, there is still much room for improvement in the availability of insulin to patients
.
Insulin drugs are one of the most expensive drugs in the world.
In 2017, Sanofi, Novo Nordisk and Eli Lilly were accused of raising prices in disguise, making life-saving drugs "unaffordable
.
" In 2019, the US Congress put pressure on insulin manufacturers to reduce prices
.
In addition, the American pharmacy benefit management company Express Scripts and the insurance company Cigna also announced the upper limit of the cost of insulin products
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Under this pressure, Sanofi launched a campaign that each person can buy up to 10 boxes of injection pens or 10 ml of insulin injections for US$99 per month
.
Eli Lilly will sell the "authorized imitation version" of its insulin lispro product Humalog 100 50% lower than the original product.

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On the occasion of the century of insulin, the FDA announced the approval of the first interchangeable biosimilar drug, namely Semglee (insulin glargine) from Viatris
.
Semglee's reference biologic drug is Sanofi's Ladder, and patients can directly replace it at the pharmacy without the intervention of the prescribing doctor
.
Stimulated by biosimilar drugs, Sanofi, Eli Lilly, and Novo Nordisk have launched preferential policies in the United States
.
Sanofi reduced the cost of insulin for uninsured patients and other cash-paying patients to $99 a month
.
Novo Nordisk and Eli Lilly began selling authorized generic drugs at half the list price or launched official low-cost versions
.
Eli Lilly has reduced the price of most insulin products to $35 per month, which is suitable for patients with commercial insurance or no medical insurance at all
.
Wal-Mart also announced plans to sell its own-brand version of the Novo analog insulin at a discount of up to 75% of the current price
.
However, in the development of new insulin products in the future, the original three giants of insulin may change
.
Although it has won the world's best-selling insulin, in 2019, Sanofi announced that it would withdraw from diabetes research and development
.
In the insulin product pipeline, Sanofi is currently mainly relying on Latsi to fight alone, and its market is being continuously eroded by other manufacturers.
Total sales of Latsi in 2020 are 3.
554 billion euros, a year-on-year decline of 8.
75%
.
In order to cope with the impact of the loss of competition in the insulin glargine market, Sanofi has launched a new insulin glargine Toujeo in 2015
.
However, Sanofi's progress in the development of new insulins is not optimistic.
The SGLT1/2 inhibitor Zynquista, which was developed in cooperation with Lexicon, ceased cooperation as the trial for expanded indications failed
.
The other two overlords, Novo Nordisk and Eli Lilly, are still working hard to develop a better and smarter insulin in the world.

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Novo Nordisk's weekly injection of icodec insulin injection has been in phase III clinical trials around the world, and it is expected to become the world's first weekly injection of insulin product
.
In addition, Novo Nordisk has been conducting research on stem cell therapy for the ultimate treatment concept for diabetes for more than 20 years
.
In mid-July this year, Eli Lilly also spent US$1 billion to acquire the biotechnology company Protomer Technologies, and obtained Protomer’s experimental glucose-responsive insulin drug project
.
It is understood that glucose-sensitive insulin can be turned on when the patient's blood glucose level rises and turned off again when the level returns to normal, thereby providing better blood glucose control and reducing the risk of hypoglycemia
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In addition, non-injectable insulin preparations are also a key research and development direction in the field of diabetes treatment
.
For example, Oramed Pharmaceuticals is developing a phase III clinical trial of the oral insulin drug ORMD-0801 for the treatment of type 2 diabetes
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If it can be successfully marketed, it will effectively improve the compliance and comfort of daily medication for diabetic patients
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However, the innovation of insulin is not limited to drugs, but also includes the innovation of insulin cognitive concepts and the innovation of insulin devices
.
In the previous hundred years, the gradual advancement of insulin products has been accompanied by the continuous deepening of people's awareness of diabetes
.
Nowadays, people have learned about several types of diabetes, and there are many complications of diabetes, these complications can be avoided or delayed onset, and diabetes patients need personalized treatment methods and treatment goals
.
However, humans still do not fully understand the causes of type 1 or type 2 diabetes
.
Humans also need to better understand the different subtypes of diabetes, use drugs accurately, and provide patients with personalized treatments based on the specific subtypes of diabetes
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In terms of device innovation, an improved durable injection pen for adults and children with memory function has been launched on the market
.
I believe that with the digital age and the development of wearable medical devices, related technologies can help patients use insulin better, allowing patients to make wise decisions about insulin dosage, food intake, and exercise volume, reducing errors, and reducing the daily routine of diabetes management Burden, thereby improving patient compliance
.