R&D of new drugs has revolutionized biopharmaceutical research and development

Business News Agency on September 3 hearing, Tianjin Tianshi Pharmaceutical Co., Ltd. (hereinafter referred to as "Tishri") disclosed that its flagship product compound Danshen Dripping Pills FDA (US Food and Drug Administration) Phase II clinical trials have been completed. Compound Danshen Dripping Pill is a commonly used proprietary Chinese medicine for the treatment of coronary heart disease. It has been on the market for more than 10 years and is one of the most important products of Tasly. Its annual sales exceed RMB 1.2 billion. The purpose of this phase II clinical trial was to determine the efficacy and dose response of Compound Danshen Dripping Pills in patients with chronic stable angina in the United States. The Compound Danshen Dripping Pills received the FDA's IND clinical trial approval in 1997. Later, through extensive in-depth basic research in China, the FDA started Phase II clinical trials in 2007. Clinical trials are distributed in New York, Florida, Texas, and California. The 15 clinical centers in the southeast, northwest, and midwest regions of the United States strictly follow the internationally recognized standards for GCP clinical trials. All research successfully ended at the end of 2009. Tasly said that 50 to 70 global clinical trial centers will be established in the next two years to complete the FDA phase III clinical trials. It is expected that after 3 years, compound Danshen Dripping Pills are expected to be listed in the United States and globally as pharmaceuticals.

In the past decade or so, the amount of funds invested in research and development of new drugs has continuously increased due to the continuous extension of drug discovery and research until the approval of regulatory authorities for listing. As a result, pharmaceutical companies have begun to study new strategies for drug development, and strive to reduce investment in terms of time and money. As a result, some new trends in drug development have emerged. Among them, the adoption of global synchronized drug development is an important way to increase the efficiency of drug development. Tasly’s experience coincides with this trend.

The advantages of international multi-center clinical trials

An expert from the Center for Drug Evaluation of the State Food and Drug Administration pointed out that because of the differences in drug registration and clinical trial management systems in different countries and regions, many new compounds cannot be synchronized globally starting from early clinical trials. As a result, some multinational corporations have started phase 2 or phase 3 clinical trials in phase 2 clinical trials and conducted clinical trials in multiple countries simultaneously to obtain data that can be finally used for analysis, as an application for evaluating the safety and efficacy of drug submissions to registration authorities. . However, developing countries such as China and India have a large number of population resources, a wide distribution of disease types, and relatively low research costs, which will surely become the preferred destination for multinational companies to conduct international multi-center clinical trials. In fact, according to incomplete statistics, about 20% to 30% of international multicenter clinical trials are currently conducted in developing countries.

From 2004 to 2008, the number of international multi-center clinical trials declared in China has increased from less than 20 applications per year to about 70, and remained stable. From the analysis of statistical data, it is found that about one-third of all compounds and therapeutic biological products that are declared as international multi-center clinical trials are already listed products. This shows that when multinational corporations conduct drug research and development, they usually weigh the time and efficiency of research and development, take the listing as a target, and study the indications with good prospects and high development success rate. After obtaining the marketing permission, further expand the indications. Field, to expand the benefits of drug development. This is not completely consistent with the thinking of many domestic companies in the development of new drugs. Domestic companies usually choose to conduct multiple studies simultaneously from early clinical trials to later critical confirmatory clinical trials, which not only distracts time, money, and management efforts, but also fails to conduct in-depth and thorough research on each indication. , resulting in a long period of time for the approval of new drugs to be listed and difficult.

Prof. Yao Chen from the First Hospital of Peking University, by reviewing the contents of the database registered on the Clinical Trials.gov website, summarized and analyzed clinical trials conducted in mainland China as of May 2007, and found that clinical trials sponsored by pharmaceutical companies have Of these, 58 were international multi-center trials and 39 were independently tested in mainland China. The main research subjects were tumors, circulatory diseases, central nervous system diseases, and infections. In individual trials in mainland China, clinical trials were all overseas-listed drugs. The purpose of these trials was clear: to expand the indications in China or to export to China. In the international multi-center clinical trials, 26 tested drugs have not been listed at home and abroad. Of the drugs that belong to a new class of drugs in China's drug registration classification, 23 were conducted after the dose exploration trials in the United States and Europe. The three phases of international multi-center trials conducted worldwide are mainly aimed at registering for registration in countries other than China, and also applying for registration of new drugs in China in conjunction with clinical trial data from China and international multi-center trial results.

In addition to the international multi-center clinical trials, which can provide reference for local companies in drug innovation, they can also bring practical help to local doctors and patients. Chen Ming, the registered director of Sanofi-Aventis China R&D Department, told reporters that for China, the advantages of using international multi-center clinical trial data for registration include five aspects: First, Chinese data obtained in international multi-center clinical trials A more scientific and accurate assessment of the safety and effectiveness of drugs for Chinese people is an evaluation method that is more responsible for Chinese patients. Second, in terms of time, it can speed up the listing of drugs in China. In the current regulatory environment, the use of Chinese data from international multi-center Phase III clinical trials to register, compared with 3.1 traditional registration strategies, can at least enable the time to market drugs in China to be 3 to 4 years ahead of schedule. Third, international multi-center clinical trials can reduce the waste of R&D resources. Fourth, to participate in the global synchronous R & D, the international multi-center clinical trials of new drugs in the IND stage, can rapidly improve the clinical research level of drugs in domestic hospitals, and train a large number of drug R & D personnel for hospitals and pharmaceutical companies to enhance their R & D capabilities. V. Clinical trials of new drugs are an important part of drug research and development. They are measured in units of 10 billion U.S. dollars. Even if only 15% of the trials were transferred to China, it would be a considerable amount of income.

Biomedical research and development focus

According to Fei Jia, Pharmacist at Beijing Coast International Consulting Co., Ltd., with the development of biomedical theories and technologies, humans have in-depth and comprehensive understanding of various diseases and drug mechanisms, especially molecular biology and cell biology technology. The development of the drug has made great changes in the methods and ideas of drug research. The implementation of the Human Genome Project, the elucidation of the molecular mechanisms of drug action, etc., have greatly promoted the research of new drugs in the 21st century. As traditional pharmaceutical companies are at a disadvantage in biotechnology, their monopoly in the pharmaceutical sector is being challenged by biotechnology companies. According to the analysis of clinical applications approved by the FDA in the United States, biotechnology companies have gradually become a major force in the study of certain specific areas such as cancer, cardiovascular and infectious diseases.

As of December 31, 2008, the FDA approved a total of 99 biotech drugs (genetically engineered drugs or monoclonal antibody-based drugs) on the market. In 2007, there were a total of 110 drug sales that exceeded 1 billion U.S. dollars, including 29 biotech drugs. In other words, more than 26% of biotech drugs are "bombers." This is a rather alarming proportion, indicating that biotechnology drugs have a huge market demand and a very high degree of intensive. Although there are tens of thousands of non-biotech drugs and only 81 of them have annual sales of more than 1 billion U.S. dollars, the proportion of "bombers" is less than 1%. More surprisingly, due to the rapid development of genetically engineered antibody drugs in recent years, 16 of the “super blockbuster” drugs with sales of more than US$4 billion in 2007 were biotech drugs.

From the analysis of the biopharmaceutical product structure, cancer treatment drugs are the focus of research and development of biopharmaceuticals. Of the biotech drugs researched in 2008, 254 were used for cancer treatment and accounted for half of all drugs in clinical trials. The new drug targets tumor cells and at the same time minimizes the damage to healthy tissue, triggering an exemplary shift in treatment. Now, biologic drugs allow doctors to treat cancer as a curable chronic disease. Taking Bristol-Myers Squibb as an example, the anti-tumor biologic drugs currently being researched cover many areas such as liver cancer, lung cancer, gastric cancer, and leukemia.

New R&D Platform Based on Systems Biology

Professor He Qiyang of the Institute of Biotechnology, Chinese Academy of Medical Sciences believes that although the traditional methods of drug discovery have been widely used in the past 30 years and have been fruitful, their use has also revealed low efficiency, slowness, and success rate. The low disadvantages, especially the large gap between the huge capital investment and its low output rate. Many candidate compounds are difficult to fully and completely reflect the correlation between drugs and diseases, often in preclinical and clinical trials, due to inefficiency or ineffectiveness, poor pharmacokinetics (short half-life, low bioavailability), acute or subclinical Chronic poisonous side effects and other issues were forced to withdraw from research and development. This is the most important "bottleneck" for drug discovery based on a single drug target. After the system biology method was introduced into drug development, many system biology-based drug development prediction platforms, such as PhysioLab Platform, IPA, etc. were established, which allowed the pharmaceutical industry to see the dawn of overcoming difficulties.

The sequencing work from the yeast, E. coli genome to the human genome was completed, marking the arrival of various “omics” development eras such as genomics, proteomics, transcriptomics, and metabonomics. Life science research began to gradually focus on an integrated and comprehensive analysis of the various levels of the entire biological system, as well as various levels and mutual dynamic information, in order to obtain a more comprehensive understanding of complex biological systems. The system biology born on this basis is a university subject that studies the composition of all components (genes, mRNAs, proteins, etc.) in a biological system and the relationship between these components under specific conditions and is characterized by integrity. In addition to biological data, system biology is also intertwined with multiple disciplines such as computational sciences, informatics, medicine, and mathematics to more fully describe the operating laws and regulatory mechanisms of biological systems.

Systems biology combines "discovery science" and "hypothesis-driven science" with each other to simulate the model and drive drug research from pure descriptive science to predictive science. . In drug research and development, mathematical simulation models have been established based on data from one drug to one disease, resulting in a variety of system-based drug discovery platforms. This has become a new strategy for drug discovery and research.

The occurrence of many major diseases, such as tumors, neurodegenerative diseases, and diabetes, is the result of multi-gene effects and multi-steps, which may be one of the reasons for the poor efficacy of drugs targeting a single target. Experts at home and abroad generally believe that system biology analyzes multiple targets of disease at the same time and comprehensively elucidates the mechanism of drug action. Combining the development of such disciplines as structural biology and computational biology, under the common promotion of technologies such as high-concentration drug screening technology and bio-mathematical models, a system-based drug research and development platform will bring revolutionary changes to new drug development.