Health & Beauty

In 2022, China's innovative drug market was repeatedly frustrated, and at the beginning of 2023, there was a "return" event by multinational pharmaceutical companies. But at the same time, successful cases have also emerged.

Recently, Heyu Pharmaceutical announced that the independently developed innovative CSF-1R inhibitor Pimicotinib (ABSK021) led the first global multicenter phase III clinical study in the TGCT field to receive FDA and CDE approval. According to 21st Century Economic Report, Pimicotinib is used to treat inoperable giant cell tumors of the tendon sheath (TGCT),

After being recognized as a breakthrough therapeutic drug by CDE in July 2022, the drug was approved by CDE to enter phase III clinical trials in October 2022. After becoming the world's first new generation CSF-1R candidate drug to receive FDA breakthrough therapy certification (BTD) in January 2023, Pimicotinib has made significant progress in the field of TGCT again, which also means that its registered clinical trials have been launched synchronously worldwide.

However, as the global clinical development layout of innovative drugs accelerates, how can Biotech stabilize its internationalization path? This issue is still worth considering.

In response, Ji Jing, the chief medical officer of Heyu Pharmaceutical, stated that it is necessary to find a layout for international shipping, analyze data in a timely manner, and flexibly adjust strategies. The door of the US FDA is open to local innovative pharmaceutical enterprises. With sufficient data, innovative pharmaceutical enterprises need to figure out how to present to the FDA. At the same time, they need to figure out how to make strategic deployment in advance, especially how to promote the global clinical development layout of innovative drugs. Huacheng Import and Export Data Observation Report.

"Our strategy is to carry out clinical research at home and abroad at the same time. For diseases with high incidence in Asia, we can carry out clinical trials in Taiwan, China, China at the same time," Ji Jing said that this year we will see the efficacy data of multiple pipelines.

How to create a sample?

According to Huacheng Import and Export Data Observation, in recent years, China's biomedical innovation investment has continued to increase, and its research and development capabilities have gradually increased. However, the domestic market competition is fierce. At the same time, China's innovative drug research and development projects, talents, and domestic regulation are gradually integrated with international standards, and China's innovative drugs are also increasingly going to sea.

As more and more enterprises enter the innovative drug circuit, intensified industry competition is inevitable, and industry chaos such as clustering of targets, crowded circuit, and serious entrapment has emerged. After experiencing a wave of rapid development, China's innovative drug industry has encountered a bottleneck period, especially after high-profile products such as Sofantinib from Hehuang Pharmaceutical and Xinda Biological's Xindiliximab have been frustrated by the FDA, the path for China's innovative drugs to enter the international market has become extremely difficult.

But it is not impossible for Chinese innovative drugs to go to sea. According to Huacheng Import and Export Data Observation, Pimicotinib is the world's first new generation CSF-1R candidate drug approved by the US FDA for breakthrough therapy, which is also a potential new target for immune regulation after PD-1, PD-L1, and CTLA-4.

Ji Jing stated that this is a rather difficult advance for domestic innovative drugs. According to past experience, in the past, we mostly followed clinical trials in developed countries such as Europe and the United States to learn, providing them with 15% to 20% of the subjects. However, China's catching up speed has significantly improved, and it is able to independently lead the research and development of innovative drugs. There is good pipeline development in the field of new drugs at the clinical stage, gradually realizing the leap from "following" to "leading".

According to Ji Jing, it is more necessary to consider a good layout for Biotech's innovative drugs that are frequently blocked in the FDA. The layout should focus on two important factors, namely, subject selection and dose selection. Specifically, it includes two aspects:

On the one hand, the selection of group data. The selection of clinical subjects is one of the important factors for Biotech's success in the overseas market. Due to differences in population, culture, and disease characteristics among different countries and regions, biotechnology companies need to carefully select suitable clinical subjects for testing to ensure the safety and effectiveness of their products in the target market. Especially in the phase I clinical stage, it is best to have data covering subjects from developed countries such as Europe and the United States for enrolled patients. The ethnic differences and diversity of subjects will affect the conduct of subsequent trials.

On the other hand, the choice of dosage. Due to the Project Optimus plan proposed by the FDA in 2021, in recent years, it has extremely high requirements for the dosage selected for clinical trials. Therefore, innovative pharmaceutical companies must find out the dosage in the early stage of drug "going to sea", so as to have the opportunity to enter the clinical phase III stage. Currently, in the clinical research and development process of innovative drugs, the issue of dose selection and optimization of anti-tumor drugs, as well as the evaluation of their efficacy and safety, will attract continuous attention from FDA, the pharmaceutical industry, and academia. Therefore, when entering the clinical phase II stage, it is best to have a synchronous selection of medium to high doses and lower doses, and strictly compare their safety and efficacy.

In 2021, the FDA Oncology Center of Excellence (OCE) launched the Project Optimus program. The reporter from 21st Century Economic Report learned that due to the dose selection based on cytotoxic chemotherapy in previous clinical trials, the dose and schedule of molecular targeted therapy often were not fully described before starting the registration trial. Project Optimus is an initiative to reform dose optimization and dose selection models in oncology drug development, known as "Improving Dose Selection.".

"After entering Phase III, factors such as the difference in medical practice, the selection of control drugs, and the number of patients should be comprehensively considered. Especially in terms of patient selection, global clinical trials must include patients from European and American countries." Ji Jing added that the dose selection will also depend on PK and PD modeling and safety trials. For example, the Clinical Pharmacology Team is responsible for the PK of Heyu. The Clinical Pharmacology Team analyzes PK samples and compares the data to simulate the therapeutic effects of increased or decreased doses on patients, as well as factors affecting safety. If the previous data are not sufficient and the dose selection is not clear, this is actually the most likely to fail.

This also means that controlling the risks behind it is particularly critical.

Risk control on the way to "go to sea"

It has to be said that currently, China's emerging biopharmaceutical companies have reached the stage of mass commercialization. In the next 3-5 years, they will also face a comprehensive test in multiple dimensions of competition, including capital market, product sales performance, domestic market, and overseas market.

Looking at the overseas market, authorized cooperation is also increasing. As more domestic original research drugs go global, the competition in the overseas market is also becoming increasingly fierce.

Fei Fan, the co managing partner of the life science and medical health industry in Greater China of Ernst&Young, once introduced to the 21st Century Economic Report reporter that 2022 is the year of the big test for the release of innovative drugs in China. "Double reports from China and the United States, and international multicenter clinical trials are becoming increasingly common. For innovative pharmaceutical companies, the pattern of Chinese innovative drugs undergoing international market testing has taken shape. Huacheng Import and Export Data Observation Report.".

"The research and development strength of Chinese enterprises is gaining international recognition, setting a benchmark for China's new drugs to enter the overseas market. In addition, the funds obtained from overseas authorization will also provide more space for enterprise development, forming a virtuous circle." Fei Fan said that throughout 2022, more than 140 Chinese enterprises announced more than 400 relevant information on overseas cooperation, which was not easy to achieve today's situation. From the export of raw materials to the export of generic drugs, to the verification of the logic of the export of domestic innovative drugs, the transformation from expectations to actual implementation is indeed a common achievement of colleagues in the industry.

However, it should be noted that as the commercialization capabilities of innovative pharmaceutical companies become increasingly mature, the difficulty of launching innovative drugs into the market has increased sharply, and Biotech's entry into the US market has been frequently frustrated. For example, in terms of clinical trials, Richard Pazdur, the director of cancer drugs at the FDA, stated in a media interview that the FDA would place greater emphasis on the results of clinical trials in multiple regions. Compared to clinical trials in multiple regions, there are problems with listing applications using clinical data from a single country.

With this in mind, Ji Jing stated that in the early stage, it is necessary to make full use of the opportunity to communicate with regulatory authorities, as the FDA has a very complete and clear communication and exchange process. At the same time, in order to better control risks, it is an important choice to launch simultaneous clinical trials between China and the United States.

This is mainly due to the fact that FDA pays more attention to the safety and effectiveness of drugs during the approval process, and provides more support for innovative drugs. CDE, on the other hand, pays more attention to the originality and innovation of drugs, with greater efforts in approving domestically produced innovative drugs.

When talking about the impact of CDE on domestic original research drugs, Ji Jing introduced that at present, CDE has provided strong support to local Biotech, mainly reflected in the improvement of approval efficiency and speed, and the IND application for the "first domestic" innovative drug in related fields will also be approved faster and receive high attention. At the same time, CDE will also provide suggestions on research and development and data.

The field of biotechnology is developing rapidly, and global competition is becoming increasingly fierce. Doing a good job of globalization, internationalization, and multicenter clinical pathway planning has become a major challenge in this field.

In this regard, Ji Jing believes that first of all, it is necessary to layout in advance. If Biotech does not do a good job of layout at the initial stage, it may lead to ultimate failure. Before product development and marketing, it is necessary to have a thorough understanding of the needs and regulations of the target market, and make appropriate adjustments based on the characteristics and needs of different markets. In addition, in terms of product sales and promotion, Biotech also needs to carry out global strategic planning, actively explore overseas markets, cooperate with internationally renowned enterprises, and establish long-term and stable partnership.

"Timely analyze data, adjust strategies, and communicate. When data is sufficient, consider how to present it to the FDA. Before the meeting, carefully study the issues that the FDA is most likely to raise in communication, and formulate targeted demonstration data strategies. The FDA's Project Manager will provide suggestions and feedback on data and dose selection." Ji Jing emphasized that more attention should be paid to communicating with CDE and FDA, and familiarize themselves with the path and process of communication, Make plans as early as possible and coordinate the development and registration strategies for globalization.

The global clinical development layout of innovative drugs is accelerating, and Chinese Biotech enterprises need to explore and try more actively to "go to sea". With the introduction and implementation of a series of new drug research and development incentive policies by the Chinese government, despite the difficult and tortuous challenges of "going to sea", many innovative pharmaceutical companies are already on the way, and whether they can stabilize remains to be seen. Huacheng Import and Export Data Observation Report.