The Omicron mutant with faster transmission speed and more hidden transmission process has led to the emergence of a large number of infected people since its emergence. In addition, many people have been vaccinated with covid-19 vaccine in the early stage. Most of the infected people are asymptomatic or mild, which is making the epidemic prevention and control more difficult.
To deal with the Omicron epidemic, in addition to the dynamic clearing of non-medical prevention and control means and vaccines, the development of covid-19 specific drugs is equally important. At present, there is also an urgent need for drugs that can block the transmission of the virus at an early stage. Small molecule oral covid-19 drugs with convenient administration, easy production and easy storage are expected.
At present, a number of domestic oral covid-19 drugs have been put into research and development, but when can they be listed?
domestic drugs under development
Since January this year, the Omicron mutant first appeared in Tianjin and has spread to many provinces in China. Since March, China has reported more than 500000 cases of covid-19 infection.
In the race against covid-19 virus, more domestic small molecule oral drugs have been put into research and development. Recently, there has been frequent progress in domestic drug research and development.
In early April, Xiansheng Pharmaceutical (02096. HK) announced that the company was developing an anti covid-19 virus small molecule sim0417. As the first approved clinical 3CL target covid-19 oral drug in China, it has achieved the first subject medication.
Also in early April, Kaifa Pharmaceutical (09939. HK) released the key data of phase III global multicenter clinical trial of oral covid-19 drug prochloramide in the treatment of mild and moderate non hospitalized covid-19 patients, and the results boosted the market. 99% of the subjects in the clinical trial are from the United States. The inclusion does not exclude the subjects from being vaccinated, nor does it require the subjects to have risk factors. It has been shown that the drug can effectively reduce the hospitalization / mortality of covid-19 patients, especially for all patients taking the drug for more than 7 days, and the corresponding protection rate is 100%; In subjects with high risk factors (especially in the middle and high age group), it can significantly reduce hospitalization / mortality; In addition, it can significantly and continuously reduce covid-19 virus load and improve covid-19 related symptoms.
Tong Youzhi, founder, chairman and CEO of pioneer pharmaceutical, said: “these data rigorously prove the clinical efficacy of prochloramide in covid-19 population (mainly infected by delta and Omicron variants) and are statistically significant.”
Then, in April 19th, Shanghai Junshi Biosciences Co.Ltd(688180) ( Shanghai Junshi Biosciences Co.Ltd(688180) .SH, 01877.HK) registered a website of the China clinical registration center, which evaluated the efficacy and safety of VV116 compared with PAXLOVID in the treatment of mild to moderate New Coronavirus pneumonia in a multicenter, single blind, randomized, and clinical study.
Vv116 is an oral nucleoside anti covid-19 drug developed by Shanghai Junshi Biosciences Co.Ltd(688180) and Suzhou Wangshan wangshui biomedical Co., Ltd. Paxlovid is a 3CL protease inhibitor for covid-19 developed by Pfizer, which was approved to be listed in China in February this year Shanghai Junshi Biosciences Co.Ltd(688180) the head-to-head clinical trial launched this time can compare the efficacy of the two drugs, which has aroused strong attention from the outside world. The first financial reporter learned that the study was completed in April 2022, and the first patient was enrolled and administered.
Similarly, on April 19, Geli Pharmaceutical (01672. HK) announced the antiviral cell experiment of oral small molecule covid-19 candidate drug 3CL protease inhibitor asc11. From the preliminary data, it is superior to similar drugs. The company expects to submit the application for clinical trial in the second half of 2022 and complete the phase I clinical trial in healthy subjects by the end of 2022.
Wu JINZI, founder, chairman and CEO of geley pharmaceutical, told China business that asc11 plans to develop three covid-19 indications, which are respectively used for the treatment of mild and severe covid-19 and the prevention of covid-19.
In addition to the above-mentioned enterprises, real biology, Shan Dong Kexing Bioproducts Co.Ltd(688136) ( Shan Dong Kexing Bioproducts Co.Ltd(688136) . SH), Yunding Xinyao (01952. HK) and other enterprises are also working hard to develop small molecule oral covid-19 drugs. It is worth mentioning that individual enterprises have developed two or more models.
For example, Shanghai Junshi Biosciences Co.Ltd(688180) is also developing a 3CL protease inhibitor vv993 for fighting covid-19, which is in the preclinical development stage.
“Vv116 and vv993 are drugs or candidate drugs developed for different key and conservative targets in the virus life cycle. In addition to being used alone and giving full play to their respective clinical advantages or characteristics, they also have the development prospect of ‘combined antiviral drugs, complement each other and bring out good results’.” First, financial and economic people said.
when will it be available
Most of the action mechanism of small molecule oral covid-19 drugs is to eliminate the virus by interfering with the replication of the virus itself. Because it mainly acts in cells, the intracellular process is relatively conservative and is not easy to mutate, so the effect is not easy to be affected by the mutant strain. In addition, convenient administration and easy production, storage and transportation are also a major advantage of this kind of drugs.
Shanghai Junshi Biosciences Co.Ltd(688180) replied to the first finance reporter: “the production capacity will not become the bottleneck of the follow-up industrialization of vv116.”
Some markets believe that small molecule oral covid-19 drugs are expected to become the government’s strategic reserve drugs in the future.
Soochow Securities Co.Ltd(601555) analyst Zhu Guoguang believed in the research report released in March that the state would negotiate the price of domestic small molecule drugs in the process of participating in the strategic reserve. “The price of Chinese reserved drugs can refer to the price of Tamiflu. Assuming that the average price of domestic small molecule drugs negotiated by the government is about 200300 yuan / course of treatment, the government will start the reserve of specific drugs within three years from 2022, and the annual reserve drug market of small molecule drugs in China is about 22.4-42 billion yuan.”
At present, there is no domestic small molecule oral covid-19 drug on the market in China, and there is also a lack of small molecule oral drugs that can treat a large number of patients with mild and moderate diseases and general risks. At present, there is only one small molecule drug approved for marketing, and it is imported, that is, Pfizer’s paxlovid, but it is only used for the treatment of light and common adult patients with severe high-risk factors within 5 days of onset.
At the same time, the price of the drug is not cheap, as high as 2300 yuan a box.
At present, domestic small molecule oral covid-19 drugs are stepping up the development of indications for mild and moderate diseases. The main targets of relevant drugs are 3CL protease, RNA polymerase (RdRp) and androgen receptor (AR) antagonists.
Specifically, 3CL protease inhibitor can inhibit the action of 3CL protease, so as to prevent a series of subsequent replication activities of the virus. RNA dependent RNA polymerase (RdRp) is the polymerase in the process of viral RNA replication. RdRp inhibitors inhibit the effect of RdRp and can also interfere with or inhibit viral replication. Androgen receptor (AR) antagonists can exert antiviral effects in two ways: one is to regulate the key proteins ACE2 and TMPRSS2 of host cells and inhibit the invasion of covid-19 virus into host cells; Second, activate nrf-2 pathway, inhibit the production of inflammatory factors and prevent the occurrence of factor storm, which can reduce the severity of moderate and severe covid-19 patients.
Most of the domestic small molecule oral drugs under research are still in the preclinical research stage, or have just entered the clinical research stage.
Among the clinical trials carried out in China, the domestic small molecule covid-19 drugs with the fastest progress are azvudine for real organisms, prochloramide for developing pharmaceutical industry and vv116 for Shanghai Junshi Biosciences Co.Ltd(688180) the three drugs are RdRp inhibitor, AR antagonist and RdRp inhibitor respectively.
Among them, azvudine, a real organism, has completed phase III clinical trials, and the data are waiting to be unblinded. The global multicenter phase III clinical trial of prochloramide in the treatment of mild to moderate covid-19 patients developed by the pharmaceutical industry was completed in Shenzhen Third People’s Hospital on February 10, 2022 Shanghai Junshi Biosciences Co.Ltd(688180) of vv116 was used in the international multicenter, double-blind, randomized, placebo-controlled phase II / III clinical study for the treatment of mild to moderate covid-19 patients. The first patient was enrolled and administered in Shanghai public health clinical center in March 2022.
However, when related drugs can finally be listed still faces a certain test.
Recently, a person engaged in the research and development of small molecule oral covid-19 drugs told the first finance and economics reporter that the assessment standard of covid-19 oral therapeutic drugs for phase III clinical treatment takes the improvement of symptoms as the “clinical end point”, especially “reducing the mortality of low / critical patients”, which has brought some challenges to the current clinical trials of relevant drugs. The reason is that people infected with Omicron now, Due to the basis of vaccination in the early stage, the infected people are mostly asymptomatic or mild, and the number of severe and hospitalized patients is relatively small.
“At present, there are not many deaths due to covid-19. According to the current market assessment standards, it is difficult for domestic small molecule oral drugs to speed up the market. We call for ‘reducing the viral load’ as the assessment standard. After the viral load comes down, the nucleic acid will also turn negative soon. This assessment standard is more in line with the current reality of prevention and control.” Covid-19 drug clinical research and development experts told the first financial reporter.
