How does hard-core "black technology" empower innovative drugs to "go overseas"?

21st Century Business Herald reporter Ji Yuanyuan Intern Yan Shuo reported from Shanghai In the past decade, China's pharmaceutical innovation industry has grown rapidly, and a number of high-quality innovative enterprises with global competitiveness have come to the fore, and it has become a new trend to accelerate the layout of the innovative drug market. It is worth mentioning that in the past, large domestic pharmaceutical companies mainly relied on the Chinese market for their revenue, while overseas, most of the revenue sources of mature multinational pharmaceutical companies came from the international market, and "going overseas" has become a must for Chinese pharmaceutical companies.

According to Pharmacube data, in 2023, there will be nearly 70 innovative drug license-out transactions in China, with a total disclosed transaction value of more than US$35 billion. In 2024, the momentum of domestic innovative drugs going overseas will continue, and relevant data shows that in January 2024, there were a total of 18 license-out transactions of Chinese pharmaceutical companies, an increase of 260% from 5 in January 2023.

Some industry reports also disclosed that although the total amount and volume of China's biomedical investment and financing in 2021-2023 have declined significantly, pharmaceutical companies have actively carried out external BD cooperation, and China's innovative drugs have ushered in a record high. However, with the increase in the number of China's innovative drugs "going overseas" and the low success rate of drug research and development, there may be a wave of returns in the future. The "going to sea" outbreak window will close in 2-3 years.

In fact, from project approval to approval of new drugs, the innovative drug track needs to go through many links such as preclinical research, clinical trials, new drug registration and marketing, and after-sales supervision, and each link may face the risk of failure. The "going overseas" of innovative drugs is a very complex process, among which the clinical trial stage is extremely complex and lacks certainty, and its trial design, clinical data applicability and other issues are gradually placed in the "front of the stage".

"In the field of clinical trials, due to the high regulation of the industry, the entire industry used to be more cautious about the application of technology and relied heavily on human power to do a lot of work, such as data entry, data verification, etc., but today, we are already using AI to help with decision-making. Through the application of AI in various trial stages, we can accelerate the overseas expansion of innovative drugs. Yan Xiaoming, senior manager of Dassault Systèmes Medidata Strategic Consulting and Solutions Business Department in Greater China, told the 21st Century Business Herald reporter.

Song Le, senior solution expert of Dassault Systèmes Medidata Greater China, also told the 21st Century Business Herald that the application of digital health technology (DHT) can promote the remote data collection of participants in the clinical research of medical products, and its application scenarios can be all aspects of the medical industry. This data is mainly from the participants in the clinical study, including patients, researchers, and some operators may also contribute directly to the data in the future. The use of DHT has actually played a decisive role in the successful "going overseas" of China's innovative drugs.

AI is the key to breaking the game

In 2023, there will be frequent successes for China's innovative drugs to "go overseas", and Hutchison Whampoa, Junshi Biosciences, and Yifan Pharma have successfully entered overseas markets with innovative therapies, unique molecular structures or drug delivery methods, injecting confidence into the development of the industry.

"However, we know that whether it was in the past or now, China's innovative drugs are actually facing many difficulties in 'going overseas', taking international multi-center trials as an example, there are some problems that need to be solved in many links from research design to research plan to research execution. Yan Xiaoming said.

In terms of research and design, the track chosen for overseas listing is very different from that in China. For example, for the same indication, the standard treatment in China may be different from the standard treatment overseas, which means that the standard chemotherapy may be faced in China, but the targeted therapy that has been marketed in the United States and Europe may be faced.

For pharmaceutical companies, it is necessary to understand in advance the treatment plan to be targeted in the future, including the approximate extent of its efficacy and safety, and make a judgment on the probability of becoming a drug based on early data and product mechanism, and how confident it is to exceed the existing plan. But the reality is that the authorities are highly dependent on a limited number of publications to make critical decisions that cost hundreds or even tens of millions of dollars.

In the research planning stage, it is difficult for pharmaceutical companies to grasp the recruitment speed of local trial centers when they "go overseas". For the research planning team, many of them are based on past clinical experience, and the global trial centers often lack experience and lack of actual data to support the enrollment plan, which will lead to the trial being less than expected in the enrollment stage.

In addition, there are large differences between China and abroad in the research execution stage. For example, in China, 100% SDV (source data verification and confirmation) is generally used, that is, during the research process, CRA (clinical monitors) are sent to the research center to check whether the relevant data is consistent with the data entered into the system. In foreign countries, many have adopted RBQM (risk-based quality management) to focus on monitoring key data.

Overall, in Yan Xiaoming's view, there are two key nodes in clinical trials, one is the design of the clinical trial protocol, and the other is the speed of patient enrollment. The former determines the direction of research and is the key to success or failure, while the latter is the key to determining the speed of clinical trials. Limited literature data will bring many limitations, and companies will be affected in decision-making, and in the context of precision medicine, the complexity of study design will be greatly increased, making it more difficult to recruit patients. According to the data of research institutions and the Medidata database, 50% of clinical sites failed to enroll patients as planned, and even 37% of sites did not recruit a single patient in the study, which is self-evident in the negative impact of the study.

AI can empower all phases of international multi-center clinical trials. For example, through the application of AI and big data, companies can efficiently recruit patients overseas and achieve patient diversity, in the context of precision medicine, AI technology can synthesize external control groups without random control assignment, and then advance trials as scheduled, and at the same time, AI technology can also provide trial insights to help identify trial risks, improve the quality of trial data, and further improve trial results。

No matter how empowered, high-quality data is an indispensable supporting element in the underlying logic of AI. "The foundation of AI is data, and without data, AI systems cannot be built. At the same time, enterprises need to pay special attention to data security and privacy. Yan Xiaoming said that taking the Medidata platform as an example, its data is the aggregate data of clinical trials, and AI only uses the data of validated therapies provided by patients in the process of participating in trials, and the platform will have many rules to protect patients' privacy, so as to ensure that their intellectual property will not be shared or leaked.

"AI technology in clinical trials is a promising and expanding field, and AI technology may be the key to overcoming the current bottlenecks faced by innovative drugs in entering overseas markets, providing innovative impetus for a new model of sustainable pharmaceutical research and development, and providing the possibility of conducting trials better, faster and more cost-effectively. Yan Xiaoming said.

eCOA promotes data quality

At present, the most widely used DHT technology at home and abroad is eCOA/ePRO technology. In the global clinical trial market, dozens of policies in many countries, including the US FDA and the European EMA, explicitly encourage the use of COA data as a label statement to support new drug marketing applications. With the digitalization of clinical trials, regulatory agencies are increasingly accepting eCOA data for drug applications.

China has also issued a number of policies to explicitly encourage the use of eCOA/ePRO tools. In 2021, the mainland NMPA issued the "Guiding Principles for the Application of Patient-Reported Outcomes in Clinical Drug Development (Trial)", which officially and comprehensively focused on this technology for the first time, and last year, three patient-centered guiding principles were successively issued.

"The so-called eCOA is actually an electronic clinical outcome assessment, that is, the collection and analysis of information about patients' feelings, physical functions or survival status in clinical trials through electronic means. While ePRO refers to electronic patient-reported outcomes, ePRO can be understood as the type of data contained in the eCOA. Song Le introduced.

Why does DHT, represented by eCOA, receive so much attention and attention? In this regard, Song Le believes that almost all countries are sparing no effort to promote the concept of "patient-centered", that is, people-oriented. There are four main reasons why eCOA has received attention from regulators and the industry, two of which are in line with the people-oriented trend.

The first is that the patient participation experience is good and the burden is light, which enhances the feasibility of the technology, and the second is that the patient's medication safety is monitored, and the patient's post-medication feedback can be continuously collected through the eCOA technology. "In fact, in the clinical trial stage, the control of data, especially safety data, is very high regulatory requirements in various places, which is also a basis for the listing of new drugs, and eCOA can ensure that some important data will not be lost. Song Le added.

Thirdly, eCOA can also help improve data quality, because this data collection mode is remote, it can collect the patient's current experience and feedback in real time, and the collected data does not need to be transcribed, thus reducing the risk of data loss or data transcription errors, thereby improving data quality.

In addition, the use of eCOA can reduce the cost of clinical trials. According to public information, in terms of the overall investment of the project, the cost of eCOA is reduced by 67% compared with the paper method. The cost reduction is mainly due to the improvement of data quality, the increase in the efficiency of project operations, and the reduction of hidden costs of patient safety, compared to which the cost of electronic systems is actually insignificant.

According to a report by Healthcare IT, the eCOA market is valued at $1.4 billion in 2023 and is expected to reach $4.7 billion in 2031, with a compound annual growth rate of 15.8%, indicating that the eCOA market will show a benign development trend in the future. However, according to Medidata data, the reality in China is that the eCOA penetration rate is low, or only 5%. In the United States, the figure is as high as 80%.

"In the mainland, eCOA is still in the blue ocean market to be explored. In addition, we can also see that once Chinese pharmaceutical companies do some 'going global' projects, the proportion of eCOA will soar. I believe that in the next 5-10 years, we will see even more vigorous development of eCOA. Song Le said.

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