While Merck's new crown drug Molnupiravir was approved for marketing by the UK Food and Drug Administration, and Pfizer disclosed the interim results of phase III clinical trials, China's independently developed new crown drugs have also been promoted, and there is good news from phase III clinical trials of drugs.
At the "2021 Nanjing International New Medicine and Life and Health Industry Innovation Investment Summit" held from October 19 to 21, 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 according to incomplete statistics, there are currently 381 anti-new crown drugs in clinical research, including 4 listing applications, 108 clinical phase III, 180 clinical phase II, and 75 clinical phase I.
With a variety of COVID-19 drugs in Phase III clinical trials, who can go to the end?
Phase III results of COVID-19 drugs in China
The research and development of effective drugs for the new crown virus mainly revolves around three technical routes: blocking the virus from entering the cell, inhibiting virus replication, and regulating the human immune system, and China has deployed them on these technical routes.
At present, China's route layout of new crown drugs is also showing initial results.
On November 3, at the World's Top Scientists Pandemic and Public Health Forum, Xie Xiaoliang, winner of the 2015 Alberni Biomedical Award, revealed that the new antibody DXP-604, a new antibody to the new coronavirus jointly developed by Peking University's Xie Xiaoliang team and Danxu Biology, has been approved as a sympathetic emergency treatment drug in Beijing Ditan Hospital, and 14 patients in Beijing have been treated.
In addition, the development of pharmaceuticals (09939. HK) A new generation of androgen receptor antagonist "puklamide" under investigation has been authorized for emergency use in Paraguay, and its previous three clinical trials in Brazil initially showed that pkrutamine can reduce the risk of death in critically ill patients by 78%.
At present, the fastest progress is Tengsheng Bo Pharmaceutical Biotechnology Co., Ltd. (02137. HK) of BRII-196 and BRII-198 are two neutralizing antibody drugs. In China, the R&D team submitted a rolling application for conditional listing to the State Food and Drug Administration on October 9, and is expected to be approved for conditional listing by the end of December.
A few days ago, Jiehua Bio released the phased data of the phased clinical trial study of Lefu Energy Atomization Inhalation for the Treatment of Severe Covid-19 Phase 3, and the results showed that Lefu Energy 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 virus in the new crown patients, and advance the time of virus 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.
Lefu Energy, also known as recombinant cytokine gene-derived protein injection, is a drug that has been listed in China, and launched a treatment study on new crown pneumonia in February 2020. As can be seen from the paper "Clinical Study of Novaferon in the Treatment of Novel Coronavirus" published in the International Journal of Infectious Diseases (IJID) on August 2, Lefu energy is considered a potential antiviral drug against COVID-19 diseases that can prevent the virus from replicating and protect it from the new crown virus. In randomized trials, the antiviral effect of Lefu energy on patients with new crown pneumonia was observed, and the safety of lefu energy inhalation treatment for new crown pneumonia was high, and no side effects were observed.
Liu Longbin, CEO of Jiehua Biological Group, told the first financial reporter that based on the above trials, Lefuneng was approved for Phase III clinical trials in Canada and launched a randomized, double-blind, placebo-controlled international multi-center Phase III clinical trial to observe the clinical efficacy and safety of hospitalized severe COVID-19 patients with nebulized inhalation Lefu energy.
CBN saw from the clinical trial registration information of Clinical Trials that the study was conducted independently in two phases (Cohort A and Cohort B), both double-blind designs, Cohort A observed the preliminary safety and efficacy, and the countries participating in clinical studies included Canada, Brazil, South Africa, Argentina, Chile, Peru, Kenya, Turkey, Indonesia, Ukraine, Malaysia and other more than ten countries and more than 90 centers.
Medical staff transport patients in Komunalka, on the outskirts of Moscow, Russia, on 13 November. The cumulative number of confirmed COVID-19 cases in Russia has exceeded 9 million. Xinhua.
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.
Previously, only the U.S.-approved Regeneration Company cocktail synthesis antibody reduced viral load in mildly ill patients by 2.5 times (0.41 log10 copies/ml).
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.
In addition, regarding the "Phase III clinical study for 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.
Drugs in Phase 3 clinical trials
The ongoing COVID-19 pandemic has forced people to revisit optimistic ideas that would have been hoped to achieve herd immunity through vaccination and thus eliminate the spread of the virus.
According to Worldometers, as of 1:06 a.m. on 18 November, there were 255,672,242 confirmed cases of COVID-19 worldwide and 5,137,834 deaths. There were 577,526 new confirmed cases in a single day.
New single-day confirmed cases worldwide. Source: Worldometers
Chen Kaixian said at the above summit that in the case of vaccination coverage in many countries and regions, it still causes a new round of epidemics, which highlights the importance and urgency of the research and development of special drugs against new crown pneumonia, which is the ultimate weapon to defeat the epidemic, eliminate panic and protect mankind.
To find effective treatments as quickly as possible, the World Health Organization has led a solidarity trial at the global level aimed at comparing the safety and efficacy of drugs.
There are two main paths to find new crown specific drugs: one is biological macromolecule drugs, mainly antibody drugs, which have made rapid progress in global research and development, but have poor effects on mutated virus strains, and are high costs and inconvenient to use by injection. The other type is small molecule drugs, which can inhibit virus immersion and replication, which have a broad-spectrum effect on various variant strains, have the advantages of home oral treatment, easy to quickly start large-scale production emergency supply, low cost, good accessibility, suitable for use by a wide range of people, etc., and have become the centralized force point for countries to accelerate the development of anti-new crown pneumonia drugs.
Among the small molecule drugs under research in the world, the rapid progress includes pkrutamine, which pioneered the pharmaceutical industry, DC402234 and VV936 from the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences, MERCK's nucleoside antiviral drug EIDD-2801, and Pfizer's oral new coronavirus master protease inhibitor PF-07321332.
Seven of the COVID-19 drugs in Phase III clinical trials are of great interest, namely Remdesivir from Gilead (approved with annual sales of more than $5 billion); Mönoopipide (first approved for marketing in the UK through eucalyptus applications); Pf-07321332, an oral antiviral protease inhibitor from Pf-07321332 (phase 3 interim clinical data blinded); and Yoshi Shiono's oral antiviral protease inhibitor S-217622 (phase 1 clinical end, Phase 2/3 clinical initiation in late September; Roche's RNA polymerase inhibitor AT-527 (Phase 2 clinical failure); Jiehua Bio's broad-spectrum antiviral drug Lefu energy (4 Phase 3 clinical trials, effective data have been obtained); pioneering and pharmaceutical androgen receptor antagonist pkrutamide (Phase 3 clinical).
What are the research data for these high-profile COVID-19 drugs?
Remdesivir is mainly used in severely ill hospitalized patients, and its benefit index is "shortened hospital stay of 4 days", and the virus clearance time is not disclosed;
Regenerative element neutralizing antibodies (cocktail therapy) are mainly used in mild and moderate non-hospitalized patients, with a 70% reduction in main or fatality, which can reduce the viral load by 0.41Log10 copies/ml and shorten the time of symptom remission by 5-7 days;
Monupilvir is mainly targeted in mild non-hospitalized patients and is ineffective in severely inpatient patients, with no difference in virus clearance time compared with the placebo group;
Pfizer PF-07321332 is mainly aimed at mild non-hospitalized patients, is ineffective in severe patients, can reduce hospitalization and mortality by 89%, and the virus clearance time is not disclosed;
Lefu energy is mainly for severe patients, can reduce respiratory failure and mortality by 58.3%, the early recovery rate of patients is 67.8%, the virus clearance time is 7 days, and 1.38Log10 copies/ml can be reduced.
It can be seen that the search for new crown drugs has been started from multiple angles, targeting mild, moderate and severe diseases. Clinical experts believe that drugs that are effective for mild diseases can reduce the development of more patients into severe diseases and reduce deaths, which is important for the treatment of new crown pneumonia, but for the treatment of severe patients, effective drugs are also needed, which can reduce the deaths caused by severe diseases. Therefore, whether it is for mild or severe diseases, effective COVID-19 drugs are needed.
But the clinical expert also said that finding a new coronavirus drug is not an easy task, and further observation of the long-term efficacy and safety of the drug is still needed.