List of domestic drug R&D failure cases in 2021

In the process of clinical development of a new drug, it is not an exaggeration to describe it as "cautious, like walking on thin ice"
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At the time of leaving the old and welcoming the new, reviewing the failure cases of domestic drug research and development in 2021 and summarizing the essential and objective reasons behind the failure may be the key to success and reducing mistakes
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Drug R&D risks and benefits coexist.
Drug innovation and R&D have always had the characteristics of "three highs and one long", that is, high investment, high return, high risk and long cycle
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According to Pharmapremia's statistics based on nearly 10,000 clinical trials, the success rates of phase I, II, and III clinical trials are 63.
8%, 33.
2%, and 60.
1%, respectively
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Among them, the phase II clinical failure rate is the highest, with a success rate of only 33.
2%; even if the phase II clinical trial is passed, the phase III clinical trial success rate is only 60.
1%
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The success rate of oncology drug research and development is far lower than the clinical success rate of non-oncology drugs
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According to statistics from the Biomedtracker database in 2016, the success rate of oncology drugs from phase I to market launch was only 5.
1%, less than half of that of non-oncology drugs
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In Phase III clinical trials, the success rate of oncology drugs was only 40.
1%, while the success rate of non-oncology drugs exceeded 60%
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The use of biomarkers can greatly increase the success rate of clinical trials
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Biomarkers refer to biochemical indicators that can mark changes or possible changes in the structure or function of systems, organs, tissues, cells, and sub-cells, and can be used for disease diagnosis, judgment of disease stages, or evaluation of the safety and effectiveness of new drugs in target populations Sex
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According to Biomedtracker data, the use of biomarkers can increase the success rate of clinical trials from 8.
4% to 25.
9%
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Even in Phase II clinical trials where the risk of clinical research and development is the highest, the use of biomarkers can significantly increase the success rate of research and development by 18%
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Typical cases of domestic pharmaceutical R&D failures in 2021 2021 is a bumper year for my country's innovative drugs
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A total of 24 innovative drugs were approved by the NMPA for marketing, setting a new high in the past three years
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NMPA official website data shows that there are 14 new drugs approved in 2020, and the number of new drugs approved for marketing in 2019 is 16
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Behind the rapid increase in the number of new drugs approved, we must also clearly realize that the research and development of innovative drugs is by no means easy, and risks and benefits coexist
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According to incomplete statistics, in 2021, companies such as Biotech, Renfu Pharmaceutical, and Zejing Pharmaceutical have terminated the research and development of a batch of innovative drugs under its umbrella
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(1) On February 8, Biotech announced that its ADC drug BAT8001 (recombinant humanized anti-HER2 monoclonal antibody-maytansine conjugate for injection) phase III clinical efficacy indicators did not reach the preset level compared with the control group It was decided to terminate the clinical trial of the project, and the total R&D investment of the project was 226 million yuan
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In March, Biotech announced the termination of the clinical development of BAT8003 (recombinant humanized anti-Trop2 monoclonal antibody-maytansine conjugate for injection) and BAT1306 (recombinant humanized anti-PD-1 monoclonal antibody injection)
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These two projects have invested more than 110 million yuan in total
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Comment: In 2021, Biotech frequently broke his wrist, first with HER2 ADC product BAT8001, then TROP2 ADC product BAT8003 and PD-1 monoclonal antibody BAT1306
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For the two ADC products, according to the announcement, the progression-free survival (PFS) of BAT8001 in the treatment of advanced breast cancer did not reach the preset superiority target compared with the lapatinib/capecitabine group
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The BAT8003 also uses the batansine technology similar to BAT8001, which has a higher risk of clinical development
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The active suspension of BAT1306 may be a wise move.
China is the region with the most intense PD-1 competition.
There are more than 80 PD-1 monoclonal antibodies developed or jointly developed by Chinese companies.
Competition to further increase R&D costs
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However, the natural late-comer disadvantage after the listing makes drug sales not optimistic, and the price of Paimrizumab 40,000 in 2 years is a helpless compromise of the company
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(2) On August 17, Zejing Pharmaceutical issued an announcement that Donafenib tosylate tablets in the treatment of stage III of advanced colorectal cancer above the second line showed that the median overall survival (mOS) did not reach the preset value compared with the control group.
The goal of superiority
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The company decided to terminate the further development of Donafenib monotherapy for this indication
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Comments: Donafenib is an oral multi-target, multi-kinase inhibitor class of small molecule anti-tumor drugs.
The first-line indication for the treatment of advanced hepatocellular carcinoma was approved for marketing in June 2021
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Although the trial of Donafinil for the treatment of second-line and advanced colorectal cancer failed, the company has not been defeated.
Active research is being carried out on Donafinil's monotherapy and combination therapies for other indications, such as Donafinil.
Phase III trials for the treatment of locally advanced/metastatic radioiodine refractory differentiated thyroid cancer have been successful
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(3) On November 12, Renfu Medicine issued an announcement to terminate the research and development of a new class 1 drug RF-A089 capsule (ALK inhibitor)
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RF-A089 capsule is currently in Phase I clinical, and its indication is ALK-positive locally advanced or metastatic non-small cell lung cancer
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Comment: The competition for ALK inhibitors has become fierce.
At present, five drugs with the same target have been on the market in China.
At the end of 2020, Ensatinib of Betta Pharmaceuticals will be on the market, and it will be successfully included in the national medical insurance catalog in 2021
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In fact, in patients with non-small cell lung cancer, the proportion of ALK rearrangement is only 5%, but based on the large domestic lung cancer population, the number of patients is still considerable
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However, Renfu Pharmaceutical said that it is becoming more difficult to recruit patients in clinical research, which reflects the tightening of clinical resources and the intensification of competition
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(4) In August, Xinlitai announced that it intends to terminate the "Nanatinostat" "Exclusive License Agreement" signed with VIRACTA of the United States.

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In 2018, Xinlitai signed an agreement with VIRACTA to obtain the exclusive license to use Nanatinostat in Mainland China
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Nanatinostat is an antineoplastic, antiviral drugs associated with oral, useful for the treatment of cancers associated with EB virus, such as EB virus positive lymphoma, nasopharyngeal cancer and gastric cancer
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Comments: Xinlitai focuses on innovative research and development in the field of cardiovascular and cerebrovascular diseases
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Chemical drug R&D projects and scientific research teams are deployed in chronic disease drugs such as cardiovascular and cerebrovascular, diabetes, and orthopedics .
Nanatinostat, as an oncology drug, has certain differences with Xinlitai's focus on diseases
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At present, under the background of intensified overall competition among pharmaceutical companies, a high degree of focus may be the key for companies to achieve corner overtaking, and the result of diversified development is often diversified deterioration.
Therefore, although Xinlitai is stripping its product pipeline, it will take a long-term view.
Looking at it, it is one of the focused ideas
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(5) On November 5, Deciphera announced the latest results of the Phase III clinical study of repetinib in patients with gastrointestinal stromal tumor (GIST) who had previously been treated with imatinib
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Compared with the standard treatment of sunitinib, the study failed to achieve the primary endpoint of improving progression-free survival (PFS)
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Comment: In June 2019, Zai Lab reached an agreement with Deciphera to obtain the exclusive license to develop and commercialize Repetinib in Greater China
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In March 2021, the State Food and Drug Administration approved the marketing application of Repetinib for adult patients with advanced gastrointestinal stromal tumor (GIST) treated with 3 or more kinase inhibitors including imatinib
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Although repetinib has achieved success in the fourth-line treatment of GIST, the clinical failure of front-line treatment will undoubtedly have an impact on the subsequent development of the product
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In addition, although repetinib has shown good efficacy in the second-line treatment of GIST in phase I clinical trials, the final clinical failure indicates that the early clinical evidence may not fully translate into clinical benefits.

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(6) On July 27th, Incyte announced that the FDA had rejected the company's Retifanlimab BLA application for locally advanced or metastatic anal squamous cell carcinoma (SCAC) adult patients who have advanced disease or are intolerant to platinum-based chemotherapy
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The reason is that the objective response rate is lower than expected, and the other is that the number of patients included in the trial is small
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Comment: In 2019, Zai Lab obtained the exclusive rights of Incyte's PD-1 monoclonal antibody Retifanlimab in Greater China with a down payment of USD 17.
5 million and a milestone fee of up to USD 60 million
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In fact, Zai Lab is developing indications for non-small cell lung cancer and endometrial cancer for Retifanlimab, and has not participated in the research of anal squamous cell carcinoma
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However, the failure of clinical trials still caused investors to panic.
On July 27, Zai Lab's share price fell by more than 12%
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Conclusion There are different reasons for the termination of the research and development of innovative drugs.
The author believes that the main reasons include breaking the wrist (active) and compelling (passive)
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Breaking the arm of a strong man refers to the fact that in the research and development of innovative drugs, companies choose to actively suspend research and development due to changes in the market competition pattern or concerns about intensified market competition in the future
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Under the background of China's hot research and development of innovative drugs, corporate innovation projects have sprung up, but behind the splendid research and development, there are often cold and cruel commercialization realities hidden
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Therefore, it may be a wise move for a strong man to break his wrist.
"Early failure" at certain moments means "early gains" and focus funds and energy on more promising strategic varieties
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For example, Biotech took the initiative to suspend the PD-1 inhibitor BAT1306, and Renfu Medicine terminated the Class 1 new drug RF-A089 project, which is quite general
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Forced means that the drug is rejected by the drug regulatory department because of its efficacy or safety is not as good as expected
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Drug R&D is like walking on thin ice, and R&D failure is even more commonplace
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Even though some drugs passed the most exciting Phase II clinical trial, they ended up in the Phase III clinical trial.
It is regrettable that it is embarrassing: after all, companies have invested a lot of money and effort, but the results are not satisfactory
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But perhaps, this is the essence of drug research and development, always disappointed in hope, and hoped in disappointment
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This is true for drug development, and so is life
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