Covid-19 epidemic has not subsided. As an important tool for epidemic prevention and control, covid-19 oral drugs have become a hot topic of concern.
Southwest Securities Co.Ltd(600369) previously, the global covid-19 oral drug market was estimated to be billions to tens of billions of dollars. From the perspective of China, there are more than ten covid-19 oral drugs in the research and development stage, among which vv116 of Shanghai Junshi Biosciences Co.Ltd(688180) (1877. HK, Shanghai Junshi Biosciences Co.Ltd(688180) . SH), azvudine of real life, prochloramide of developing pharmaceutical industry (9939. HK) are ahead.
Development progress of covid-19 oral drug in China source: Huachuang securities
Although it has not been officially approved, covid-19 oral drug concept stocks were once popular in the market with the disclosure of the progress of relevant R & D and commercial cooperation. Shandong Xinhua Pharmaceutical Company Limited(000756) ( Shandong Xinhua Pharmaceutical Company Limited(000756) . SZ), as a distributor of azvudine production, had harvested 13 boards in 17 days. As of the closing of the 18th, it closed up 0.56% to 25.15 yuan / share.
Who can take the lead in domestic covid-19 oral medicine is undoubtedly the most concerned problem of the outside world. After being approved, how to win the competition in this 10 billion track? Some pharmaceutical analysts pointed out in the interview that covid-19 oral medicine first depends on its own efficacy, and cost, price and production capacity will also become important influencing factors.
centralized disclosure of R & D and commercialization progress of domestic covid-19 oral drug
Since the covid-19 epidemic in early 2020, covid-19 therapeutic drugs have been highly expected. The use scenarios of neutralizing antibody therapy that has made progress in the early stage are concentrated in hospitals. Since October 2021, MSD has published the interim analysis results of a phase III study of molnupiravir, and the use of more convenient oral small molecule covid-19 therapeutic drugs has further entered people's vision.
Huachuang securities research report pointed out that oral medicine is the last piece of puzzle to end the fear of the epidemic. It can be taken at home and has low social cost; Target collection, not afraid of virus mutation; Normal temperature storage and transportation, fast global distribution; The cost is much lower than the advantages of antibodies.
At present, there is only one covid-19 oral drug approved in China, which is Pfizer's nimatovir tablets / ritonavir tablets combination (paxlovid). The first domestic covid-19 oral medicine will go to who's home. There are many guesses through the published research progress.
According to the "Huashan infection" wechat official account on May 18, the results of an open and prospective cohort study to evaluate the effect of vv116 on the nucleic acid negative time of patients with non severe Omicron infection were published in the journal emerging microbes & infections on May 18. This is the first peer review report on the clinical research results of "domestic" anti covid-19 virus drugs on Omicron infected patients.
The data showed that the nucleic acid negative time of patients infected with Omicron using vv116 within 5 days after the first positive nucleic acid test was 8.56 days, which was less than 11.13 days in the control group. In symptomatic patients, vv116 given within the medication time range of this study (2-10 days after the first nucleic acid positive) can shorten the nucleic acid negative time of patients. In terms of drug safety, no serious adverse reactions were observed.
The above vv116 is a new oral nucleoside drug, which is jointly developed by Shanghai Institute of pharmacy, Chinese Academy of Sciences, Wuhan Institute of Virology, Chinese Academy of Sciences, Xinjiang Institute of physical and chemical technology, Chinese Academy of Sciences, Wangshan wangshui and Central Asia drug R & D center, Chinese Academy of Sciences. In October 2021, Shanghai Junshi Biosciences Co.Ltd(688180) announced a cooperation with Wangshan wangshui to jointly undertake the global clinical development and industrialization of the drug.
According to the information disclosed in Shanghai Junshi Biosciences Co.Ltd(688180) previous announcement, at present, the drug has carried out international multi center phase III clinical research, started phase III clinical research for moderate and severe diseases and phase II / III clinical research for mild and moderate diseases, and has completed the enrollment of the first patient. It is noteworthy that the head-to-head phase III clinical of the drug and Pfizer paxlovid is also advancing, and the first patient was enrolled and administered in April.
In addition to the research and development progress, the cooperation agreement around covid-19 oral medicine has also caused a lot of agitation in the secondary market recently.
On May 10, Zhejiang Ausun Pharmaceutical Co.Ltd(603229) ( Zhejiang Ausun Pharmaceutical Co.Ltd(603229) ) announced that Qizheng pharmaceutical, a wholly-owned subsidiary of the company, had recently signed the entrusted processing and production framework agreement and drug entrusted production quality agreement with real organisms for the processing and production of azvudine tablets.
Azvudine is a class 1 new anti AIDS drug targeting RNA reverse transcriptase. It is a class 1 new anti AIDS drug independently developed by real organisms. It was approved for marketing in July 2021. Azvudine has attracted much attention due to its research and development in covid-19 treatment. Industry analysts believe that azvudine phase III is about to be clinically blinded and declared for listing.
In addition to Zhejiang Ausun Pharmaceutical Co.Ltd(603229) , previously Shandong Xinhua Pharmaceutical Company Limited(000756) , China Resources Double-Crane Pharmaceutical Co.Ltd(600062) ( China Resources Double-Crane Pharmaceutical Co.Ltd(600062) ) also announced that they had reached cooperation agreements with real creatures on azvudine, etc China Resources Double-Crane Pharmaceutical Co.Ltd(600062) signed the framework agreement on the entrusted processing and production of azvudine tablets, which is valid for ten years Shandong Xinhua Pharmaceutical Company Limited(000756) signed the strategic cooperation agreement with real life, and real life agreed that Shandong Xinhua Pharmaceutical Company Limited(000756) is the manufacturer and distributor of azvudine and other products in China and other countries agreed by both parties.
From market rumors to the disclosure of the announcement of the cooperation agreement, azvudine allowed enterprises to reap multiple trading limits. There was once a saying that "if you touch azvudine, you will rise the limit". Although there was a slight correction, the upward momentum did not stop. On May 18, Zhejiang Ausun Pharmaceutical Co.Ltd(603229) once rose more than 4% to close up 0.27% China Resources Double-Crane Pharmaceutical Co.Ltd(600062) once rose more than 4.5% and closed down 3.88%.
Another leading domestic covid-19 oral drug is prochloramide, which is a new generation of androgen receptor antagonist. It was also considered to be the first approved covid-19 oral drug. Recently, the drug has not released new news. The most recent news is that on April 6, Kaifa pharmaceutical released the key data results of phase III global multicenter clinical trial of prochloramide in the treatment of mild and moderate disease non hospitalized covid-19 patients, reversing the previously unsatisfactory interim analysis results.
domestic covid-19 drugs how to compete for 10 billion market
Globally, the sales of covid-19 oral drugs are at the forefront of MSD and Pfizer.
According to the previous quarterly data of the two companies, molnupiravir, the covid-19 oral drug developed by MSD, achieved a revenue of $3.2 billion in the first quarter of this year, more than half of the expected sales of the whole year. Pfizer's paxlovid had revenue of $1.47 billion in the first quarter, accounting for 69% of the U.S. market. Pfizer also predicted that the drug's annual sales would be $22 billion.
How to deal with potential competition from outside China after domestic covid-19 oral drugs are really on the market?
Wu JINZI, founder, chairman and CEO of Geli Pharmaceutical (1672. HK), previously said in an interview with surging journalists that there is no approved domestic covid-19 oral drug in China. The earlier it goes on the market, the more likely it will have a greater market share, but this does not mean that latecomers have no opportunity.
Wu JINZI believes that too many drugs in any disease field, even to the extent of involution, will lead to slow sales. However, at present, covid-19 oral medicine has not reached this stage, and it may not be available in the next few years. It is difficult to control a virus with oneortwo drugs. With reference to the treatment of viral diseases such as AIDS and hepatitis C, there are more than a dozen or even dozens of drugs for these diseases. At present, there is only one approved imported covid-19 oral drug in China, and the domestic covid-19 oral drug still has market competitiveness.
"The first competitive point of covid-19 oral medicine is efficacy." Zhou chaoze, an analyst at Minsheng securities, said in an interview with surging news reporters that the core competitiveness of covid-19 oral medicine lies in three factors: efficacy, cost and toxic and side effects. If a covid-19 drug can be proved to have good curative effect through clinical research, and the toxic and side effects can be reduced. In addition, the molecular structure is relatively simple and the overall cost is more controllable, it can be extended to more developing country markets, and there will be a greater chance of winning in the competition.
Zhou chaoze explained that the molecular structure of Pfizer paxlovid is relatively complex, resulting in high raw material cost. In contrast, molnupiravir of MSD has simple structure and low cost. As for toxic and side effects, they will be written into the drug instructions in the future, which will affect people's choice of buying drugs to a certain extent.
how does production capacity affect covid-19 oral medicine
Although no domestic covid-19 oral drug has been approved, there are many layouts around production capacity.
The 2021 financial report of Kaifa pharmaceutical also mentioned that it currently has a production capacity of 1 million people / month of prochloramide, and it is expected to reach a production capacity of 50 million people / year by the end of 2022. The clinical trial application of covid-19 oral drug asc11 of gelly pharmaceutical will not be submitted until the second half of the year, but Wu JINZI also talked about the production capacity in the above interview, saying that gelly pharmaceutical is also optimizing the process, reducing costs and improving production capacity.
Real biology has reached azvudine production cooperation with a number of enterprises, which mainly solves the problem of production capacity. In this regard, Zhou chaoze told surging news reporters that it is not surprising that a drug chooses multiple cooperative manufacturers. The supplier of raw materials of any drug is unlikely to bet the whole supply chain on one enterprise. If the enterprise has problems due to the epidemic or other force majeure, the whole supply chain will have problems.
"If covid-19 drug is approved, it has certain strategic reserve significance. For the role of strategic supply guarantee, diversified supply chain is also required." According to Zhou chaoze's analysis, with the increase of production capacity, the overall cost is expected to decline further, and there is room for further decline in the pricing of covid-19 drugs in the future.
However, Zhou chaoze also stressed that production capacity is essentially an amplification effect, and the core still depends on the efficacy of drugs. The curative effect of a drug is OK, and the toxic and side effects are controllable. If the production capacity is relatively larger, the average cost will decrease. This is an influencing factor on the cost side, but not all influencing factors.
covid-19 oral medicine benefits the upstream and downstream industry chain
Covid-19 oral medicine not only has an impact on relevant R & D enterprises and cooperative enterprises, but also has potential benefits to the upstream and downstream industrial chain.
Citic Securities Company Limited(600030) research report believes that the potential demand for the production capacity of domestic small molecule covid-19 drugs is large, which is expected to bring billions of yuan of incremental orders to China's cdmo industry. Over the past 3-4 years, the demand for many small molecule innovative drugs at home and abroad has continued to catalyze the high outlook of China's cdmo industry. If domestic small molecule covid-19 drugs are approved, it is expected to further improve the sustainability of the high outlook of industry demand, especially for companies that have not previously announced large order cooperation, the increase of potential order demand may be relatively more significant.
Soochow Securities Co.Ltd(601555) believes that the rapid progress in China, including Shanghai Junshi Biosciences Co.Ltd(688180) vv116 and the real biological azvudine, are in phase III clinical stage. With the gradual completion of phase III clinical trials of oral covid-19 therapeutic drugs vv116 and azvudine, vv116 will be approved one after another. In particular, vv116 has been released in the pricing system of Uzbekistan, which is about 40% off that of paxlovid. With the approval of China, there is a large demand for intermediates and APIs. If 12 tablets per person and 300mg tablets per person, about 360 tons of APIs and more than 500 tons of key intermediates 49-1 are required per 100 million people, it is estimated that the market of 8-10 billion is expected to benefit the relevant API leading companies.
