21st Century Business Herald reporter Zhu Ping, intern Hu Bingyue, reported in Beijing
Anti-COVID-19 drug attention continues to rise.
Not long ago, Merck's new coronavirus oral drug Molnupiravir was approved for use, and then Pfizer released interim clinical data on EPIC-HR, a Phase 2/3 clinical study of the new crown oral drug Paxlovid. China also has relevant layouts and preliminary results, such as the development of the pharmaceutical androgen receptor antagonist "pukrutamine" was authorized for emergency use by Paraguay, and at the end of October officially launched the phase III clinical trial of severe hospitalized patients; the two neutralizing antibody drugs of Tengsheng Bo Drug may be approved for conditional listing by the end of December.
On November 18, the 21st Century Business Herald reporter exclusively learned that the data summary of the first phase of the phase III clinical trial of severe new crown pneumonia (Cohort A) of Jiehua Bio's broad-spectrum antiviral drug aeroviral drug aeroviral inhalation le rehab for severe new crown pneumonia was released, and its international team participating in clinical trials is currently writing a paper. The data show that the drug can reduce the respiratory failure and mortality rate of severe patients by 58.3%, and there are no deaths in the Lefu energy treatment group; increase the early recovery rate of patients by 67.8%; accelerate the negative virus in the new crown patients, and advance the time of viral negative in severe patients from 21 days to 7 days; and reduce the viral load in the patients by 24 times on the 7th day of treatment.
At present, neutralizing antibodies, small molecule oral drugs, and broad-spectrum antiviral drugs are coming one after another, when will the global anti-epidemic pattern change? At a recent industry conference, Chen Kaixian, academician of the Chinese Academy of Sciences and deputy chief engineer of the "major new drug creation" technology of the national science and technology major special project, said that in the case of vaccination in many countries and regions, it still caused a new round of epidemics, which highlighted the importance and urgency of anti-new crown pneumonia special drug research and development, and special drugs are the ultimate weapon to defeat the epidemic, eliminate panic and protect mankind.
Speaking of the successive arrival of therapeutic drugs, Jin Dongyan, a professor at the School of Biomedical Sciences of the University of Hong Kong, analyzed to the 21st Century Business Herald reporter that this will bring certain help to epidemic prevention, but in the end it depends on vaccines, especially a new generation of vaccines. "The COVID-19 pandemic has become more and more like the flu or the common cold, and the global epidemic prevention strategy will also change."
Chen Kaixian said that according to incomplete statistics, there are currently 381 anti-new crown drugs under clinical research, including 4 marketing applications, 108 clinical phase III, 180 clinical phase II, and 75 clinical phase I.
On November 4, the US pharmaceutical company Merck's new crown oral drug Molnupiravir was approved for use in the United Kingdom, becoming the world's first approved oral antiviral drug for the treatment of adult patients with mild to moderate COVID-19 symptoms. At present, the United States and the European Union are accelerating approvals, and are expected to be listed as soon as the end of 2021. The data shows that patients at high risk for severe illness who take the drug will have a 50% lower risk of death or hospitalization.
Just one day later, Pfizer announced the results of its clinical trial of Paxlovid, a specific covid-19 oral drug developed by it. The data showed that the drug reduced the risk of hospitalization or death in critically ill adult patients by 89%. It is understood that Pfizer will submit an Emergency Use Authorization (EUA) application to the U.S. government by November 25, and is expected to go public in early 2022.
Dr. Wang Zhiwei, senior vice president of BeiGene and head of chemical research and development, pointed out in an interview with the 21st Century Business Herald reporter that most small molecule drugs can be administered orally, and the preparation process is relatively simple and mature, the output is much higher than that of large molecule biological drugs, and the cost is also larger and the cost is lower; the environmental conditions for the storage and transportation of small molecule drugs are also low, which is convenient for storage or transportation.
According to Gan Tanhuan, a pharmaceutical industry analyst at CITIC Securities, compared with the new crown therapeutic antibody drugs that have been listed, small molecule oral antiviral drugs such as Molnupiravir have several advantages: the convenience is strong, and patients can go to medical institutions for injection orally; the treatment cost is low, and the overall treatment cost is only about 30% of the neutralizing antibody drugs; the production capacity bottleneck is small, mass production can be achieved quickly, and accessibility is expected to spread around the world; the mutant strain is relatively immune, with certain curative effects; and medical resources are saved. Reduce the burden on medical institutions.
In fact, prior to the approval of Mornupiravir, in the field of small molecule drugs, two drugs had been approved for marketing or emergency use for the treatment of COVID-19, namely Remdesivir (injection) of Gilead and Baretinib (tablets) of Eli Lilly Pharmaceuticals.
In addition, there are also neutralizing antibodies known as "special drugs" for the treatment of new crown pneumonia, which have also made rapid progress recently, and the earlier ones are the neutralizing antibody cocktail therapy REGN-COV2 developed by Regeneron, the neutralizing antibody LY-CoV555 jointly developed by Eli Lilly and AbCellera of Canada, VIR-7831 jointly developed by VirBiotechnology and GSK, all of which have entered the therapeutic II/ Phase III clinical trial phase.
In China, it includes JS016, which was jointly developed by Junshi Biology and the Institute of Microbiology of the Chinese Academy of Sciences, and BRII-198 of Tengsheng Bo Pharmaceutical, as well as two drugs being developed by Sinopharm Group, namely crown-specific immunoglobulin and anti-new coronavirus monoclonal antibodies. Among them, Tengshengbo drug has made rapid progress, and has published its randomized double-blind controlled international Phase 3 clinical trial data, in 837 cases of new crown pneumonia patients at high risk of disease progression, compared with placebo, monoclonal antibody combination therapy reduced the compound endpoint of hospitalization and death by 78%,
And it is planned to be listed before the end of December this year, and the relevant person in charge of Tengsheng Bo Pharmaceutical also confirmed the news to the 21st Century Business Herald reporter.
On November 11, yiqiao Shenzhou (301047. SZ) said that since the outbreak of the epidemic, the company has continued to develop a series of biological reagents related to the new crown virus, some of which can be used to support the research and development of new crown specific therapeutic drugs, such as new crown virus S protein, 3CL protease reagent, etc. On November 14, Hanyu Pharmaceutical released the news that it intends to cooperate with the Institute of Microbiology of the Chinese Academy of Sciences to develop a new coronavirus peptide nasal spray drug.
Among them, remdesivir has a certain controversy, although it has been listed in the United States in 10 years in 2020, but it has not been recognized by the WHO. On 20 November 2020, the WHO issued a conditional recommendation to oppose the use of remdesivir in hospitalized patients. On October 15, 2020, the World Health Organization released the results of clinical trials of remdesivir, hydroxychloroquine and other drugs, and among the patients tested, the number of patients using remdesivir was the largest, reaching 2750.
But the final findings showed that in terms of overall mortality, duration of treatment with ventilators and length of hospital stay, the drugs used in these trials all had little or no effect on the treatment of COVID-19.
Recently, the 21st Century Business Herald reporter found that China also has a "new use of old drugs" broad-spectrum antiviral drugs have made new progress. On November 2, Jiehua Bio released the data of the first phase of the phase III clinical trial of the antiviral drug nebulized inhalation lefu energy treatment for severe new crown pneumonia on its official website.
Lefu energy, also known as recombinant cytokine gene-derived protein injection, was officially approved for marketing by the State Food and Drug Administration on May 25, 2018 for the treatment of chronic hepatitis B.
In February 2020, the Xiangya School of Medicine of Central South University conducted a Phase II clinical study evaluating the clearance of the new coronavirus by nebulization inhalation, which was enrolled in a total of 89 patients with ordinary and severe covid-19. The results of the study showed that more than 60% of patients who received Lefu Energy Nebulization Inhalation therapy achieved the new crown virus to negative within 6 days.
At present, Lefu energy has been approved by Canada and Japan to directly carry out phase III clinical trials, which are being carried out in nearly 100 hospitals in 13 countries around the world, covering covid-19 patients from asymptomatic infected people, mild, ordinary to severe patients, and the third-party international clinical research organization IQVIA is responsible for related clinical trials.
Among them, the study of Lefu energy treatment of severe COVID-19 was a randomized, double-blind, placebo-controlled international multicenter Phase III clinical trial to observe the clinical efficacy and safety of nebulized inhalation Lefu energy treatment hospitalized patients with severe COVID-19.
ClincalTrials clinical trial registration information shows that the study was conducted independently in two phases (Cohort A and Cohort B), both were double-blind design, Cohort A observed the initial safety and efficacy, and the countries participating in the clinical study included Canada, Brazil, South Africa, Argentina, Chile, Peru, Kenya, Turkey, Indonesia, Ukraine, Malaysia and other more than ten countries and more than 90 centers.
The first phase (Cohort A) was designed to enroll about 40 cases, and 45 cases were actually completed. The Cohort A clinical trial has been completed, the data analysis report has been submitted to the Independent Data Committee (DSMB) for review and discussion, and the safety and efficacy data confirmed by the DSMB have been officially blinded.
The phase II (Cohort B) clinical trial was designed to enroll about 780 cases and is currently in the process of enrolling patients.
From the results of Cohort A's research, it was found that the effect of Lefu energy for the severe treatment of new crown pneumonia was remarkable: the virus turned negative in the Lefu energy treatment group for 7 days, and the placebo group turned negative for 21 days, and Le Fu Energy showed a good effect of clearing the new crown virus; compared with the placebo group, the respiratory failure and mortality rate of severe patients were reduced by nearly 58.3%, and the death cases occurred in the placebo group, and there were no deaths in the Le Fu Energy treatment group; the effect of Le Fu Energy treatment in reducing the viral load of severe patients was significant. The 7th day Le rehab group had a 24-fold reduction in viral load (1.38 log10 copies/ml) compared to the placebo group.
Liu Longbin, CEO of Jiehua Biologics, stressed to the 21st Century Business Herald reporter that all data are directly reported to the Independent Data Committee (IDMB) composed of internationally renowned experts after the third-party international clinical research organization IQVIA completes the internal review according to the procedure, and after the IDMB is discussed and approved, it is archived for the drug regulatory machine to verify and then provided to the enterprise. Standard International Phase III clinical trial data enterprises do not have the right to modify.
Phase III clinical trials for asymptomatic, mild and common COVID-19 are also underway. Liu Longbin said that the "Phase III clinical study on the treatment of asymptomatic to ordinary type of new crown" was launched urgently in August 2021, led by Academician Wang Fusheng, academician of the Chinese Academy of Sciences, director of the National Clinical Research Center for Infectious Diseases, and expert of the State Council Joint Prevention and Control Mechanism Scientific Research Expert Group, mainly to observe the negative data of the virus after Lefu energy treatment (mainly to observe patients infected with Delta variants), to provide scientific data and basis for discussing the "combination of prevention and treatment" strategy of Lefu energy for the prevention and treatment of new crown in China. About 200 patients are expected to be enrolled, and the study is ongoing, mainly collecting patients from port hospitals, and more than 20 patients have been observed.
Among them, regarding the "Phase III clinical study on the treatment of non-hospitalized mild COVID-19", initiated by Japanese researchers and just received emergency approval from PMDA, the drug regulatory department of the Japanese Ministry of Health and Welfare, it is expected to enroll about 200 cases and start in early November.
It is also understood that Lefu Energy has global patent protection and market access rights, and has obtained approval from the drug regulatory authorities of more than 10 countries, including G7 developed countries to G20 countries, from North America, South America, Africa, Asia to Europe, etc. to directly carry out Phase III clinical trials.
The "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Eighth Edition)" jointly issued by the National Health Commission and the Bureau of Traditional Chinese Medicine pointed out that in the process of emergency clinical trials of antiviral drugs, a number of clinical trials have been carried out successively, although no antiviral drugs have been found to be effective through strict "randomized, double-blind, placebo-controlled studies", but some drugs may have a certain therapeutic effect after clinical observation and research. At present, there is a consensus that drugs with potential antiviral effects should be used early in the course of the disease, and it is recommended to focus on patients with high-risk factors for severe illness and a tendency to severe disease.
As an "old medicine", whether Lefu energy can truly carry the banner of "broad spectrum" still needs more verification.
Since the outbreak of the epidemic, there have been three rounds of rebound in the global epidemic, all accompanied by a large-scale increase in the number of confirmed cases. The World Health Organization's director-general said in late July that the world had entered "the early stages of a third round of outbreaks". In China, since 2021, the domestic epidemic has shown a trend of multi-local sporadic, of which since September, Fujian, Heilongjiang and other places have appeared in the multi-center characteristics of the epidemic, and there have been more local cases and related cases.
In fact, the reason why oral drugs are extremely concerned is because the new crown epidemic has had a great impact on the world, directly threatening human life and health, spending a lot of manpower and material resources on epidemic prevention, and seriously affecting the global economic development.
For example, in order to curb the spread of the epidemic, many countries have actively taken prevention and control measures to restrict or prohibit group activities internally to reduce the risk of crowd gathering; externally, border control has been implemented and strict travel restrictions have been adopted. In order to alleviate the impact of the COVID-19 epidemic on the global economy, central banks in some countries have successively announced loose monetary policies such as interest rate cuts and active fiscal policies including tax cuts, investment, refinancing, etc., to boost the economy.
China has also invested heavily in epidemic prevention and control. Since the outbreak of the new crown epidemic, China has promoted epidemic prevention and control through various means such as encouraging vaccination, strengthening regional control, nucleic acid testing and antiviral drugs for all employees. According to Xiong Xianjun, former director of the Department of Pharmaceutical Service Management of the National Medical Insurance Bureau, as of the end of March 2021, 24 billion yuan had been prepaid to vaccination institutions. According to the official website of the National Health Commission, as of November 16, 2021, 31 provinces (autonomous regions and municipalities directly under the Central Government) and the Xinjiang Production and Construction Corps have reported a total of 2,402,897,000 doses of covid-19 vaccine.
In Liu Longbin's view, there are two main lines of defense for epidemic prevention and control.
"The first line of defense: mainly preventive measures, mainly relying on the new crown vaccine, the primary purpose of vaccination is to prevent the normal population after vaccination from contracting the new crown virus, in order to block the spread of the new crown, the secondary purpose is to reduce the degree of illness of new crown patients, reduce severe illness and death, and hope to restore normal social and economic life through mass vaccination." Liu Longbin pointed out to the 21st Century Business Herald reporter.
The second is the second line of defense, which is mainly based on antiviral therapy and mainly relies on specific anti-coronavirus drugs. Special drugs are mainly "treatment", and they have also achieved "prevention". After the virus in the patient's body is removed, the patient is no longer contagious and cannot be the source of infection, which not only saves the patient, but also blocks the transmission of the new crown. Only special drugs need to be provided to patients, close contacts, and high-risk groups for treatment and prevention, which greatly reduces economic costs. If there are special anti-coronavirus drugs, the new crown epidemic can be cut off without lockdown, which greatly reduces social costs and maintains normal social and economic life. It is of great significance to the prevention and control of the epidemic.
For the arrival of neutralizing antibodies, small molecule oral drugs, and broad-spectrum antiviral drugs, Jin Dongyan, a professor at the School of Biomedical Sciences of the University of Hong Kong, believes that this will bring certain help to epidemic prevention, but in the end, it depends on vaccines, especially a new generation of vaccines.
In fact, the current domestic advocate is a combination of "vaccine + special drug". Many people in the industry also believe that the combination of antiviral drugs and new crown vaccines can achieve the desired effect compared to simply using one way.
Ding Sheng, dean of the School of Pharmacy of Tsinghua University and director of the Global Health Drug Research Center, also pointed out in an interview with the 21st Century Business Herald that in the context of the current epidemic, drugs and vaccines will not be in a state of trade-off, and the two are complementary.
"The advent of the new crown special drug is equivalent to forming a double insurance together with the vaccine, and it cannot replace the role of the vaccine." People cannot be treated with drugs after infection, because long-term side effects and adverse reactions of drugs are always present, so from this point of view, the prevention and control methods taken around the world are to first achieve basic immunity through vaccines. I think vaccines will play the most important role in ending the epidemic, which is the truth that infectious diseases cannot be broken. Zhang Yuntao, chief scientist of Sinopharm China Biologics, said.
"After the vaccination rate increased, the lockdown became less and less, or even extinct. Austria imposes a lockdown or stay-at-home order for those who do not receive the vaccine, and Singapore provides that infected people who do not receive the vaccine pay their own medical expenses. In fact, the new crown epidemic has become more and more like the flu or the common cold, no one will carry out a large-scale lockdown or large-scale nucleic acid testing for the flu, and the global epidemic prevention strategy will also change. Jin Dongyan told the 21st Century Business Herald reporter.
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