Who can surpass the "Lipur" 20 years ago?New targets to reduce lipids

Is there any room for innovation?

On October 9, 2002, FDA officially confirmed that India's generic drug company Lan Boxi became the first company to submit the "Lipcao" imitation application. Pfizer's "Lipcao" is the world's first drug with a sales of $ 10 billion in sales. It is a well -deserved "medicine king" before the advent of the era of targeted drugs.

The magical variety always has a day to complete the historical mission, which is the iron law of the pharmaceutical industry. With the launch of cheap generic drugs, the treatment needs of the "three highs" have been greatly met, so that many years have not occurred in the field of slow diseases in the world.

The world may change today.

In 2015, Ansin and Sanofi gave two PCSK9 drugs for the lipid -lowering market at the same time. Since then, a new round of lipid -lowering drugs have been settled worldwide.

The full name of PCSK9 is the pre -protein transformed enzyme -proof bacteriophyll 9. It is the third gene found in human metabolism. Therefore, it has become the latest popular target for lipid -lowering drugs. The target is the absolute king of blood lipids, which is a Histein drug represented by "Lipur".

According to Mine.com, in 2021, the market size of the PCSK9 market at home and abroad was close to $ 2 billion. But as of June this year, only 3 PCSK9 drugs in the world were listed, and less than 50 projects were developed. On June 13 this year, Cinda Bio's PCSK9 drug Torlaisab apply for listing, which is expected to become the first domestic PCSK9 drug. After Cinda, Hengrui, Junshi, Kangfang and other head innovative pharmaceutical companies are also developing this. Drugs for targets.

To "injection" monoclonal anti -resistance, can really defeat the cheap lipid -lowering medicine for orally?

The next "Jetin"

In fact, when Indian enterprises started to imitate "Lipur" in 2002, Pfizer could enjoy a 9 -year patent protection period.

Hisatin drugs have been listed one after another since the 1990s, and patents are concentrated before 2010. "Lipcao" is a variety that has persisted for a long time. According to Pfizer's patent lawyer Jeffrey Mels, he recalled: When he heard that a company wanted to imitate "Lipcao", it felt like "a pirate ship pushed his own ocean wheel".

Judging from the statement at the time, Pfizer was actually reluctant to give up his identity as the "largest pharmaceutical factory in the universe". After all, after the chronic disease, Pfizer did not accumulate too much anti -cancer targeted drugs, and Pfizi faintly felt that he might miss a era.

In fact, there are still room for development.

In 2003, scientists at the NECKER-EFANTS Malades Children's Hospital of France found that a gene called PCSK9 seemed a bit of a little effect on maintaining the stability of cholesterol in the human body. Human liver surface has a low -density lipoprotein receptor that can break down cholesterol, and PCSK9 can bind to the receptor to destroy its ingredients. The "harmful" low-density lipoprotein cholesterol (LDL-C) cannot be decomposed and will enter the blood in large quantities, which will eventually lead to inception and other diseases.

The principle of statin drugs is to directly suppress the production of bad cholesterol. The PCSK9 inhibitor is to restore the normal cholesterol function of the human body. These are two completely different development ideas from Histen drugs. Following this idea, major pharmaceutical companies such as Anjin, Sanofi, Pfizer, Lili Lili have begun to follow up the research and development of PCSK9 drugs.

With the continuous deepening of research, scientists began to realize the potential of PCSK9 surpassing his drug. Generally speaking, the medium-intensity and all-in-line drugs can reduce the LDL-C by 30%. The proportion of high-intensity can only reach about 50%when administration is also prone to obvious adverse reactions. But PCSK9 inhibitors can play a more powerful role.

Some scholars have done comparisons. The effect of lowering cholesterol for single medicine PCSK9 inhibitors is about 60%, which is more than double the efficacy than Schinsham, Putacotin and other efficacy. "Lipur" Attine.

In 2019, in the "ESC/EAS Blood Liposuction Management Guide" jointly released by the European Heart Disease Society, the LDL-C index is 1.8mmol/L or above the high-risk groups of cardiovascular disease, which is 0.8 compared with the previous standards 0.8 This indicator is also widely accepted by the global clinical community, which means that more patients need to use more violent medicine.

The PCSK9 inhibitor has established an industry position.

Time is real gold and silver

Three -streaming enterprises do products, second -class enterprises do brands, and first -class enterprises are standardized. This sentence is very applicable in the pharmaceutical industry, although it is cruel.

So far, the world can be eligible to "determine standards" and serve the blood lipid abnormal standards. In fact, the 3 PCSK9 inhibitors are Alan jointly developed by Anjin's Ilu Mipida, Sanofi and Renewal Metropolitania. Xiyouzaba, as well as the SiRNA drug Inclisiran, who was approved for the first time in December 2020.

Elotabe and Alice Usura were approved to be listed in China in 2019, and entered the national medical insurance directory at the end of 2021; Inclisiran's domestic progress is still in the phase III clinical stage.

The biggest advantage of "fixed standards" is the almost monopolized to the market. Since the listing of the three drugs, sales have been increasing, especially the Anjin Yiluyaba. In 2021, it has successfully ranked among the $ 1 billion single -product club, and the market share of more than 70%of PCSK9 drugs. Looking at the domestic situation again, in 2021, the market for terminal PCSK9 inhibitors in key public hospitals in the province and municipalities was 64.63 million yuan, the growth rate reached 112%, and the overall market capacity was far greater than this number. Especially after incorporating medical insurance, the volume of the two products this year is expected.

The predecessors have already traveled a successful way, and the company that follows the trend is rushing. According to statistics from Southwest Securities, as of June this year, there were 49 projects related to PCSK9 targets worldwide, and most of them have entered the clinical stage, mainly monoclonal drugs, including 5 in the phase III clinical stage.

Data source: Southwest Securities (deadline for June 2022)

PCSK9 is the rare "blue ocean" target in the current pharmaceutical market and the lack of competition. Whoever can finish the phase III as soon as possible, who can win larger cakes.

It is worth mentioning that in the competition of PCSK9 targets, domestic companies have ran at the forefront. At present, the PCSK9 projects of Hengrui Pharmaceuticals, Junshi Biological, and Kangfang Biological Subsida Kang Rong Oriental Enterprise have opened phase III clinical at home and abroad. In addition, the pipelines of Tianguangshi, cutting -edge creatures, Tiansi and other companies have also entered the clinical stage.

Most of the time points for domestic enterprises to apply for clinicals are concentrated between 2017-2018, and they basically belong to the development of data quickly after the data of Anjin and Sanofi products are released. Among them, the clinical time for Cinda Bio and Kangfang Biological Declaration does not distinguish, and Hengrui Pharmaceutical's clinical clinical is slightly later than the previous two.

But now, the gap between several companies has opened. The Jianzhi Bureau noticed that at the end of 2021, Kangfang Biological PCSK9 inhibitors had just completed the phase II clinical and prepared to start phase III; Hengrui Pharmaceutical, which was 10 months later than Kangfang Bio It has been a few months clinically.

It is conceivable that even if the products of Cinda Bio are first approved, Hengrui or Kang Fang will keep up with the time. The time window will be short.

Monoplog is just the starting point

PCSK9 inhibitors are not worried about the rate of peers, but the hedin drugs with a deep market foundation.

According to Mine.com data, as of early June this year, there were more than 70 lipid -lowering drug brands listed in China, of which nearly 9 of them became Hisbon products. In 2021, the amount of Hasing drugs and composite drugs in the terminal of public hospitals in key provinces and cities accounted for 84.58%of the lipid -lowering market.

After decades of traditional lipid -lowering drugs, it does not mean that it can be changed. Even most doctors believe that PCSK9 inhibitors are just supplementary drugs of his class, which are mainly used in his serious intolerance, or In the case of insufficient efficacy of Jeating drugs.

"European Heart Magazine" has published data: In a survey of more than 4 million patients, the percentage of unattractive tolerance of Hisatin drugs is only about 9%. In this market alone, the PCSK9 inhibitor cannot be collected even if the R & D cost.

To change the concept of tens of thousands of cardiovascular doctors across the country, enterprises may take a lot of effort to carry out doctors' education.

Moreover, most of the current PCSK9 inhibitors are monoclonal resistance and need to be used. Cardiovascular disease is a chronic disease and requires long -term medication. Although Aliche Mipida and Elotabe can have a needle for 10 days or half a month, they are still incompatible with the medication habits of middle -aged and elderly people.

There is also a factor that after entering the medical insurance at the price negotiation, the two PCSK9 inhibitors are currently priced at 300 yuan in the country, and they will have to play twenty or thirty in one year. It costs thousands of yuan. In contrast, the domestic lipid -lowering drugs have accounted for more than 70%of the varieties. Looking at his drug, the average decrease is nearly 90%, which has long been the price of cabbage.

For many Chinese elderly people, spend two or three hundred more a month, it is also a lot of expenses.

Among the three models of PCSK9, Novartis's Inclisiran is unique. This product can directly prevent the liver from producing PCSK9 protein, and it will be injected without ten days and a half months. After 2 injections in the first three months, it is only possible to take a shot every six months.

In the first quarter of this year, Inclisiran's global sales have exceeded 2021, reaching $ 14 million. Some analysts even believe that due to the strong competition of Inclisiran, Anjin's Elotabe's sales growth may not be as good as before.

In addition, researchers are exploring more possibilities for PCSK9 targets. For example, the antonyms currently carried out by Astraon, the PCSK9 oral small molecular drugs layout of companies such as Novo, Jiayue Pharmaceutical, Xinlitai and other companies have made the fastest progress in the phase II clinical stage.

Who said that there is no new world?

Writing | Guyue

Edit ｜ Jiang Yun Jia Ting

Operation ｜ Valley

Illustration | Visual China

#Cholesterol ## ## targeted medicine#

- END -