$600 billion invested in more than 99% failure! Heng Rui attacked the grave of the new drug!

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The global research on Aβ needs to be traced back to the 1990s.

However, because there is no definite evidence of a causal relationship between Aβ deposition and cognitive decline in patients with Alzheimer's disease, the hypothesis of Aβ deposition is considered to be lacking as a theoretical basis for drug development.

Aducanumab's research and development process is like a microcosm of many pharmaceutical companies fighting Alzheimer's.

In September 2016, Aducanumab encountered a frustrating obstacle.

But Bojian did not give up and chose to continue development.

However, Aducanumab still failed to escape the fate of its predecessors.

Although the termination was announced, Aducanumab was "at the Enlightenment Meeting" in only half a year.

Therefore, it is announced that the application process for Aducanumab will be restarted and the BLA is planned to be submitted.

Although the controversy still persists, the FDA has become the "Mr.

In August 2020, the FDA announced that it had accepted the BLA of the Alzheimer's disease drug Aducanumab and granted it priority review status.

Just when the story seems to be moving in the direction of "final conclusion", the variables regenerate.

In November 2020, an advisory committee composed of external experts from the FDA said NO to Aducanumab.

The outside world's attitude towards Aducanumab has become negative again.

However, the third reversal came even faster.

At the end of January 2020, Bojian and Eisai jointly announced that the FDA has extended the BLA review period for aducanumab by 3 months.

To this day, it is unknown whether Aducanumab can be approved for listing.

01 Repeated defeats and repeated battles, MNC decisive battle AD

In the past 30 years, Bojian has not only challenged Alzheimer and failure, but also the large international pharmaceutical companies that have succeeded in succeeding.
Although many have returned without success, they even spent a lot of money.

In 2012, Johnson/Pfizer's monoclonal antibody drug Bapineuzumab phase III clinical trial failed miserably.
Forbes commented: "Pfizer and Johnson & Johnson should conduct prospective trials to verify the elimination of β-amyloid protein for the treatment of Alzheimer's disease Instead of conducting a series of large-scale experiments that may cost $400 million or more.
Research and development funds are precious and should not be wasted on wishful thinking.
"

In 2014, Roche’s AD drug Gantenerumab also failed.
In a clinical failure report on Gantenerumab and Solanezumab, foreign media stated that it would take about 12 years for a drug to go from idea to approval, and this AD research may exceed, And cost about 2.
6 billion U.
S.
dollars;

In 2016, Eli Lilly, which has been rooted in the AD field for 31 years, invested US$3 billion in this field, which was in vain as Solanezumab's Phase III clinical trial data fell short of expectations;

In 2017, Merck announced that it would stop the development of Verubecestat, a drug that reduces β-amyloid;

In 2018, Eli Lilly/AstraZeneca announced the termination of multiple phase III clinical trials of the drug lanabecestat for the treatment of Alzheimer's disease.

Although Alzheimer's disease has caused many major international pharmaceutical companies to return without success, it is also because of its difficulty and wide market that still attract large and small pharmaceutical companies and scientific research institutions.

According to statistics from the International Alzheimer's Disease Association, there are more than 50 million people with dementia worldwide, 70% of which are caused by Alzheimer's disease.
As the world's population continues to age, this number may triple by 2050.
Zion Market Research report shows that the global Alzheimer's disease drug market is expected to reach 5.
66 billion U.
S.
dollars by 2024.
This has also allowed Chinese and foreign biopharmaceutical companies to target Alzheimer's disease to develop new drugs.

According to the official website of the State Intellectual Property Office, there are over 1,800 patents related to Alzheimer's disease in China.
Among them, Green Valley Pharmaceutical has applied for a number of patents related to Alzheimer's disease around 2019.
As a domestic new drug that "filled the gap in the field of Alzheimer's treatment for no new drugs in the past 17 years", mannite sodium (GV-971, trade name 9) was jointly developed by Shanghai Institute of Medicine, Ocean University of China, and Shanghai Green Valley Pharmaceutical.
Phase 1®) has attracted much attention since its listing.
Although this drug has been controversial before, it does not affect its sale soon after its launch.
In February of this year, Nine Phase One® has completed the first patient in the Phase III clinical trial in the US Clinical Research Center.
It is expected to complete the 52-week double-blind phase research plan of the international clinical trial in 2025.
After that, Green Valley Pharmaceuticals will carry out the European and American regions.
Registration and listing of new drugs.

Except for the nine-phase one ® that has been on the market, there are currently no drugs that can really alleviate Alzheimer's disease on the market at home and abroad.
Due to the complex pathogenesis of Alzheimer's disease, the cause is still unknown, so it is still a "world problem.
" Before the "correct answer" was announced, different companies tried to "answer" in different ways based on different hypotheses.

In January 2021, Eli Lilly announced that its targeted N3pG-β amyloid antibody drug Donanemab for the treatment of early Alzheimer's disease Phase II clinical study (TRAILBLAZER-ALZ) reached its primary endpoint.
The results show that Donanemab can significantly slow down the progression of early Alzheimer's disease, and the decline in the composite index of cognition and daily function (iADRS) in patients is 32% slower than that of placebo.

After announcing the cessation of Alzheimer's disease drug development in 2018, Pfizer chose to cooperate with IBM in 2020 to jointly create an artificial intelligence (AI) model to help people predict the onset of Alzheimer's disease.
The shift from drug research and development to prediction and diagnosis is also a new "problem-solving idea.
"

Roche is similar to Pfizer's "problem-solving ideas".
In 2020, the Phase II clinical trial of the Tau amyloid antibody drug Semorinemab jointly developed by Roche's Genentech and its partner ACImmune failed to meet the primary endpoint and two secondary endpoints.
After the research and development was frustrated, Roche turned his attention to the direction of quantum computers.
In 2021, Roche and Cambridge Quantum Computing (CambridgeQuantum Computing) in the United Kingdom plan to use a quantum computer software platform to simulate chemical interactions at the quantum level to develop treatments for Alzheimer's disease.

In addition to targeting beta amyloid or Tau amyloid, some institutions choose to start with genes and want to prevent Alzheimer's disease from a genetic point of view.
The APOE4 gene has long been considered a risk factor for Alzheimer’s disease, so research institutions including famous universities such as Massachusetts Institute of Technology and Cornell University Weill School of Medicine are trying to use gene editing technologies such as CRISPR.
To change the APOE4 gene to avoid Alzheimer’s disease.

Solving an "unsolved" problem with a huge market is far more difficult and laborious than answering more questions that have already been answered, but this is also the path that innovators want to take more.

02 From generic drug to innovator's adventure

Even though many MNCs have broken down in the AD field one after another, Hengrui chose to "take one step forward" and began to try to explore more innovative and risky new areas.

To review Hengrui's nearly 30-year development history, its research and development process is divided into three stages:

The first is the generic drug stage (before 2000), the main representative products are ifosfamide, docetaxel, irinotecan, pegaspase, etc.

Ifosfamide is Hengrui’s initial adventure.
In 1992, Sun Piaoyang used 1.
2 million yuan to buy a patent for a new drug ifosfamide at a Beijing university.
This was nothing short of “astronomical” for a pharmaceutical factory with an annual profit of less than 1 million.
digital".
What I bought back was only the manufacturing process, and the clinical effect is not yet known.

In 1995, the anti-tumor drug Ifosfamide was approved for marketing, and Hengrui had its own "new drug" for the first time.
It is reported that ifosfamide/sodium thioethanesulfonate (I/M) was first approved by the US FDA in December 1988 and was listed as the highest grade 1A anti-tumor drug.

Hengrui tasted the sweetness of ifosfamide and began to plan the construction of an independent innovation system.
In 1992, Hengrui took the lead in building a 2,900-square-meter research building in Lianyungang.
In 2000, it invested 200 million yuan to establish a new research center in Shanghai.
In 2005, Hengrui advanced overseas and spent US$3 million to build an overseas research institute in San Francisco, the United States.

As a result, Hengrui entered the second stage: the stage of combining imitation and innovation (2000~2015).
In about 2000, the company began to work on the establishment of innovative drugs, and in 2003 began the first clinical application of the innovative drug Irecoxib.
During the period, the company has applied for clinical trials of 26 innovative drugs in total.
Irecoxib and apatinib were approved to be listed in 2011 and 2014 respectively.
The company achieved breakthroughs in research and development of innovative drugs and became the only domestic company with 2 “new drugs”.
Of domestic pharmaceutical companies.

Apatinib, as an anti-tumor drug independently developed by Hengrui for ten years, has continued to increase its sales since its launch.
In 2015, its sales amounted to approximately 300 million yuan.
By 2019, its sales amounted to 2.
531 billion yuan, becoming Hengrui's flagship product in one fell swoop.
Coupled with the approval of new indications, the sales of apatinib is expected to exceed 3 billion yuan in 2020.

After experiencing the short-term impact of the 2015-2016 clinical data self-examination and chemical drug classification reform, Hengrui has entered the third phase of innovation-oriented.
From 2018 to 2020, Hengrui has successively launched 4 types of pyrrotinib maleate tablets (trade name: Erini), carrelizumab, remazolam tosylate, and fluzoparib capsules.
Pound new medicine.
In the development of innovative drugs, Hengrui has basically formed a positive development trend that innovative drugs are launched every 2-3 years.

Southwest Securities predicts that in 2025, the company is expected to receive a total of about 10 innovative drugs.
The revenue of innovative drugs is expected to reach 50% of the company's revenue and the performance ratio is expected to reach 70%.
Individual innovative drugs are expected to make substantial breakthroughs overseas and initially possess international competitiveness.

After a series of major steps, Hengrui has long been at the forefront of Fast-Follow from generic drugs, and has reached a stage where it is not only satisfied with Fast-Follow.
Its involvement in the AD field is only Hengrui's more innovative approach.
Typical representative.

Original title: US$600 billion invested, over 99% failed! Roche, Merck, and AZ all broke down, Hengrui attacked the new drug "grave"!