The clinical trial of the antiviral drug redeliver in the whirlpool of public opinion was launched in Wuhan, and the first batch of patients with severe new-type coronavirus-infected pneumonia will receive medication on February 6.
In the absence of specific drugs, Redecive, which is undergoing clinical trials in the United States, has entered the public eye. This drug caused a lot of public opinion controversy due to the time of patent application and the subject.
At present, some experts are optimistic about this medicine. Academician Wang Chen, vice president of the Chinese Academy of Engineering and Dean of the Chinese Academy of Medical Sciences, also revealed in “News 1 + 1”: “According to the previous results, we have relatively high hope for Radixivir. Other drugs include Chinese medicine. All require further clinical observations to determine their efficacy. “
However, Academician Wang Chen also reminded: “There are expectations from all walks of life for this experiment, but if it has any effect, we need to wait for the results of rigorous scientific experiments.”
But people obviously expected greater. On the evening of the 6th, more than 700 patients were rumored to be effective on the Internet, and 96% of lung infections recovered miraculously in 24 hours.
In response, Professor Cao Bin of the China-Japan Friendship Hospital said: “Clinical research only started today, how can it produce results? Scientific research takes time.” Zhong Nanshan also said recently that clinical trials can speed up the green channel, but must follow the procedures.
Wang Chen, Vice President of the Chinese Academy of Engineering and President of the Chinese Academy of Medical Sciences
In addition to indinavir, chloroquine phosphate, fapilavir, and proprietary Chinese medicines have also been found to have antiviral activity in vitro. Why was radixivir selected for clinical trials? What process does a new drug take from R & D to market? NetEase’s “State ℃” column group summarized and sorted out these questions.
Effective drug for in vitro antiviral activity: Redecive is not the only one
I still remember the previous “Shanghai Drug Institute and Wuhan Virus Institute jointly found that Shuanghuanglian can inhibit new coronavirus”, causing Shuanghuanglian to be out of stock online, offline, and even the veterinary Shuanghuanglian was snatched.
“Pomp”? Shuanghuanglian and other Chinese patent medicines have indeed been found to have antiviral activity, but there is a prerequisite for “in vitro cell experiments”. However, there is still a long way to go from the in vitro cell experiments to human clinical research.
In addition to Shuanghuanglian and other proprietary Chinese medicines, drugs such as redecide, chloroquine phosphate, and fapilavir have also been found to have antiviral activity.
At a press conference held by the National Health and Health Commission on February 4, Sun Yanrong, deputy director of the Biological Center of the Ministry of Science and Technology, said that chloroquine phosphate and antiviral drugs in Chinese patent medicines have been found. Chloroquine phosphate has been marketed and has shown very good activity against new coronaviruses in vitro studies.
According to its disclosure, China is stepping up animal experiments and clinical experiments, and clinical trials have shown that chloroquine phosphate has a certain effect on this new type of coronavirus pneumonia, and further research is still being strengthened.
Jiao Yahui, deputy director of the State Administration of Health and Medical Care Administration explained that “effectiveness” is the result of cells in vitro from the laboratory. This result has a long way to go before it can be clinically effective, and it still has to go through Animal experiments, human clinical studies, etc.
Zhang Lan, director of the Pharmacy Department of Xuanwu Hospital of Capital Medical University and deputy director of the National Drug Clinical Trial Agency, also said in an interview with Peng Mei that the human body is a very complex system.
It is a substance that is effective for viruses in vitro. Can it still play after entering the human body? The same effect, in vitro and in vivo experiments are two completely different verification systems.
In other words, the success of in vitro cell experiments is far behind the clinical trials to confirm that the human body is effective.
So, in the end, what kind of long process does it take for a new drug to develop and become effective in the human body?
“New drug development is a long process”
According to the information released by the State Administration of Drug Administration, new drug development to market generally requires preclinical research (including 2-3 years of research and development and 2-4 years of clinical trials), clinical research (generally 3-7 years), There are four stages in applying for new drugs and approving them for marketing. It is understood that it has taken nearly 10 years since the start of R & D.
In the pre-clinical research phase, safety pharmacology and toxicology research should be done, that is, to prove that the effective compounds of the drug have biological activity against specific target diseases, and to evaluate possible side effects of the drug.
At this stage, all toxicity of drug-effective compounds is found mainly through in vitro tests (experiments that occur in test tubes) and animal tests. This is also the stage of preclinical experiments.
The purpose of this phase is to evaluate the pharmacological and toxicological effects of the drug, the absorption, distribution, metabolism, and excretion of the drug. The second is to conduct research on production technology, quality control, and stability.
This part of the experiment needs to be carried out at the animal level. The results of cell experiments and live animal experiments sometimes differ greatly. The purpose of this step is to determine the effectiveness and safety of the drug. The second step needs to be in compliance with GMP. The required workshop is completed.
Only after passing the preclinical test can the drug be used in human clinical trials. There are often three phases of tests for drugs used in the human body to study the properties, efficacy, and quality of drugs. 20-100 cases in the first phase, normal people, mainly for safety evaluation; 100-300 cases in the second phase, patients, mainly for effectiveness evaluation; 300-5000 cases in the third phase, patients, expanded sample size, Further evaluation.
Traditionally, clinical research on new drugs were divided into Phase I (Phase I), Phase II (Phase II), and Phase III (Phase III), and Phase II was then divided into Phase IIa and Phase IIb, largely due to tumor drug research. The concept of Phase 0 research was then proposed by people as Phase 0 / Ⅰ for early clinical research, Phase IIa for intermediate clinical research, and Phase IIb and III for advanced clinical research.
After completing all stages of clinical trials, the drug holder can submit a new drug application to the drug regulatory department after the safety and effectiveness of the drug have been proven. After the new drug application is approved by the drug regulatory department, it can be officially marketed for doctors and patients to choose from.
According to the process, new drugs need strict steps and experiments from development to market. However, the outbreak was sudden and the steps were being accelerated.
“The development of new drugs is a very long process. In such a sudden epidemic, we have no way to carry out the traditional laws of new drug development. Therefore, for the first time, the Ministry of Science and Technology organized relevant experts to carry out research and make full use of the existing With the research foundation, systematic and large-scale screening has been achieved among the drugs that have been marketed and clinical trials have been performed.
“Sun Yanrong, deputy director of the Biological Center of the Ministry of Science and Technology, was held by the National Health and Health Commission on February 4. Explained at a press conference.
Among the many antiviral drugs in vitro, Radixivir was first introduced into human clinical trials. Sun Yanrong explained that Radixivir has been used in the treatment of Ebola virus infection in foreign countries. At present, not all clinical trials have been completed abroad, but it has shown good results in related scientific research.
Therefore, the SFDA notified the applicants that the China-Japan Friendship Hospital and the Chinese Academy of Medical Sciences can conduct clinical trials. “We also look forward to achieving good results in clinical trials.” Sun Yanrong mentioned.
Red Sive: Need to wait for rigorous scientific test results
Redecive is a drug developed by the American company Gilead. The drug is a nucleotide analog prodrug that inhibits RNA-dependent RNA synthetase (RdRp). This drug under development was originally developed for the Ebola virus.
Receive has demonstrated activity against viral pathogens of atypical pneumonia (SARS) and Middle East Respiratory Syndrome (MERS). These viruses are coronaviruses and have similar structures to the 2019-nCoV novel coronavirus.
On January 31 this year (2020), a paper published by the New England Journal of Medicine on the first medical treatment, diagnosis, treatment and clinical manifestations of patients with a new type of coronavirus in the United States showed that the patients had deteriorated on January 26 On January, he received injections of redecive, and his symptoms improved significantly.
On February 2, the official website of the China-Japan Friendship Hospital announced that the China-Japan Friendship Hospital took the lead in conducting a clinical study on the treatment of 2019-nCoV new coronavirus in the epidemic area of Wuhan.
The Wuhan Institute of Virology, Chinese Academy of Sciences also said on February 4 that it was found that radescivir and chloroquine phosphate can effectively inhibit the new coronavirus in vitro. And on January 21, it applied for a Chinese invention patent (for use against new coronavirus in 2019) and will enter the major countries of the world through the PCT (Patent Cooperation Agreement) approach.
The Radixivir trial will enroll 308 patients with mild to moderate illness, and 453 patients with severe illness. Strict randomization will be performed (the drugs taken by patients will be randomly distributed according to placebo, full-volume, half-volume groups, etc.) Neither the patient nor the patient was aware of the drug or placebo) trial.
Academician Wang Chen, vice president of the Chinese Academy of Engineering and Dean of the Chinese Academy of Medical Sciences, said at the launch meeting that various circles have expectations for this test, but whether it will be effective or not, and they need to wait for the results of rigorous scientific experiments.
In response to the recently discussed anti-viral “specific drugs”, Zhong Nanshan also recently said that clinical trials can speed up the green channel, but must follow the procedure. “Many laboratories find a sign and hope to enter the clinic completely immediately. Be careful, the ethical review must pass. Clinicians still have to do according to clinical rules.”
Surging news: “National Health and Health Commission Jiao Yahui: In vitro virus suppression clinically effective”
“News 1 + 1”: On February 5th, Wang Chen, a specialist in respiratory and critical care medicine, and dean of the Chinese Academy of Medical Sciences
Xinhua News Agency: “Clinical trial of antiviral drug redecide starts in Wuhan”
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