Covid is gone? Is there still a market for the 6 new crown oral drugs in China?

Since January 8, 2023, China has officially implemented the "Class B and B tube" for novel coronavirus infection, which means that the mainland's epidemic prevention and control measures have entered a new stage.

On February 23, at a press conference of the State Council's joint prevention and control mechanism, Liang Wannian, head of the expert group of the National Health Commission's leading group for epidemic response and handling, said, "From the characteristics of the epidemic itself, it can be said that the epidemic has basically ended, but it cannot be said to be completely over. ”

So, is the domestic covid now gone?

"The new crown has not disappeared, it is just in a low-level epidemic state." Liu Jue, a member of the National Novel Coronavirus Expert Group of the National Health Commission and a researcher at the Department of Epidemiology and Health Statistics at the School of Public Health of Peking University, recently pointed out in an interview with a People's Daily health client reporter.

According to the latest national novel coronavirus infection situation released by the Chinese Center for Disease Control and Prevention, since March 3, the number of positive new coronavirus nucleic acid tests in the mainland has shown a fluctuating downward trend, and the number of positive nucleic acid tests reported daily has remained above 4,000.

At the same time, domestic new crown treatment drugs are still accelerating the approval of marketing.

Recently, Zhongsheng Ruichuang, a subsidiary of Guangdong Zhongsheng Pharmaceutical, received conditional approval for marketing of Leretvir Tablets (trade name: Leruiling ®), an oral anti-novel coronavirus 3CL protease inhibitor.

So far, the number of new crown small molecule oral drugs approved for marketing in China has increased to 6, including Pfizer Paxlovid (nematevir tablets/ritonavir tablets) and Merck Molnupiravir (monogravir capsules) 2 imported drugs, as well as 4 domestic drugs of Azvudine of Real Bio, Mindevis of Junshi Biologics, Sinoxin of Simcere Pharmaceutical, and 4 domestic drugs approved this time.

In the face of the low level of the new crown epidemic, how much is the market demand for new crown treatment? At present, the first domestic approved new crown neutralizing antibody drug has announced that it will be discontinued and will be withdrawn from the market. So, what about the new crown small molecule oral medicine?

Some analysts in the pharmaceutical industry of securities institutions told the 21st Century Business Herald reporter that adhering to small steps and non-stopping, and actively optimizing and improving prevention and control policies is an important experience in the mainland's epidemic prevention and control. At present, the pathogenicity and virulence of the Omicron variant have been significantly weakened, the full vaccination rate of the whole population has exceeded 90%, the people's awareness of the virus has been significantly improved, and the prevention and control of the epidemic in the mainland is facing a new situation and new tasks. It is also in this context that the market space for new crown oral drugs will inevitably narrow.

"Although there are still many domestic new crown drugs approved to enter the market. However, the follow-up new crown oral drug R & D enterprises will lose the first-mover advantage, and the market opportunity has been greatly reduced. However, the inspiration from the global epidemic shows that the development layout of new crown drugs is not to prepare for the epidemic or any specific crisis, but to empower the global healthcare system and promote innovation, so that it can respond quickly when responding to future challenges.

6 new crown oral drugs compete

During the epidemic and spread of the new coronavirus genes in the population, mutations and recombination will occur frequently, resulting in enhanced replication and transmission of the virus in cells, increased immune evasion ability of vaccines, and reduced cross-protection between different subbranching variants, resulting in breakthrough infection and a certain proportion of reinfection.

As of the end of 2022, there were five "variants of concern" (VOCs) identified by the World Health Organization (WHO): Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529).

In the face of the changing epidemic prevention and control situation, the National Health Commission issued the "New Coronary Pneumonia Diagnosis and Treatment Plan (Trial Version 10)" on January 7, 2023, which proposed a variety of treatment methods and medication recommendations such as antiviral therapy, immunotherapy, and traditional Chinese medicine treatment for different infected patients.

In terms of research and development of new crown treatment drugs, various pharmaceutical companies have also been continuously advancing. Up to now, a total of 6 new crown oral antiviral drugs have been approved for marketing in China, namely Pfizer Paxlovid (3CL), Simcere Pharmaceutical's Synoxin (3CL), Merck Monoravir (RdRp), Junshi Biologics Mindevil (RdRp), Real Bio Azvudine (RdRp) and the newly approved Zhongsheng Pharmaceutical Company Leruiling (3CL). The new crown oral drug Ensitrelvir (3CL) developed by Japanese pharmaceutical company Shionogi has submitted a marketing application in China, and has reached import distribution agreements and exclusive promotion agreements with Shanghai Pharmaceutical Holdings and Chia Tai Tianqing, respectively.

Liu Lihe, executive director of CIC Consulting, told the 21st Century Business Herald that most of the oral new crown drugs developed by Chinese companies are mainly targeted at 3CL protease and RdRp, the former of which the marketed drugs are represented by Pfizer Paxlovid and the latter by Merck Monoravir.

Since the 3CL protease of the virus and the cleavage site of human 3CL protease are different, the homology is low, and the drug will not interfere with the body's own protease function after entering the human body, so 3CL inhibitors are safer. At the same time, 3CL protease can screen for highly specific inhibitors, potentially designing drugs with better specificity.

RdRp is an RNA-dependent RNA polymerase, RdRp plays an important role in the process of viral replication, is the necessary and most conserved protein of RNA viruses, and the enzyme does not exist in normal host cells, anti-RNA virus effect can be effectively achieved against RdRp inhibition, and it is its similarity with nucleotide structure that provides a certain broad-spectrum antivirality.

In addition, immunomodulators, AR antagonists, etc. are also design targets for new crown treatment drugs. Immunosuppressants have the potential to treat severe patients by interfering with the synthesis and assembly of viral envelopes or nuclear shells, inhibiting the replication of viral genes, the expression of early viral genes and the proliferation of host cells, thereby affecting intracellular signaling pathways. AR antagonists can play an antiviral role in the early stage of infection by inhibiting androgen receptor function, downregulating the expression of ACE2 and TMPRSS2 from the transcription level, thereby blocking the entry of the new coronavirus into the host cell, while inhibiting the secretion of inflammatory factors caused by new coronary pneumonia, preventing the occurrence of cytokine storm, and also have a similar effect against tumors.

However, under the current reality that the new crown pandemic has basically ended, the size of the existing new crown oral drug market and whether companies can seize more market share are still up for debate. After all, Goldman Sachs had previously predicted that under normal circumstances, the size of the new crown oral drug market is expected to reach "between $15 billion and $20 billion". However, over time, it believes that more competitors will be approved and enter the market, and the price of new crown oral drugs will fall, and the market size will be between $5 billion and $6 billion.

What is the future of the new crown oral medicine?

Public information shows that among the 6 new crown oral drugs that have been approved in China, the price of Pfizer's Paxlovid is 1890 yuan / course of treatment, the price of Monoravir of Merck is 1500 yuan / course of treatment, the price of azvudine of Real Bio is an average of 445 yuan / course of treatment, the price of Simcere Pharmaceutical's Synoxin is 750 yuan / course of treatment, the price of Junshi Biologics is 795 yuan / course of treatment, and the price of Leiretvir tablets of Zhongsheng Ruichuang is 628 yuan / box / course of treatment.

When talking about the market development prospects of the new crown concept products, Wu Yifang, chairman and CEO of Fosun Pharma, told 21st Century Business Herald, "The past of the new crown has been a major and happy event for all mankind, and we cannot say that it is in the past, but I feel that the situation is undergoing fundamental changes." After 'Class B tubes', some of the original epidemic prevention products should be treated as normal products. We see that Hong Kong and Macao have opened the private market for new crown vaccination, and many countries in the world are also considering opening private markets to make the new crown vaccine a normal vaccine. The same is true for Covid treatment drugs. Wu Yifang said.

According to Fosun Pharma's 2022 financial report, Azvudine has completed medical insurance listing in 31 provinces, autonomous regions and municipalities directly under the Central Government, and has covered nearly 50,000 medical institutions across the country. According to the data, Azvudine is the first oral small molecule new coronavirus treatment drug with completely independent intellectual property rights in mainland China, which was conditionally approved by the State Food and Drug Administration on July 25, 2022 and included in the "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (9th Edition)" and "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (10th Edition)". On January 12 this year, the "Expert Consensus on Antiviral Treatment for Patients Infected with Novel Coronavirus" also included azvudine in the recommended new crown antiviral treatment drugs.

As for the newly approved Leretevir tablets, when talking about the market prospects of the product, Chen Yonghong, chairman of Zhongsheng Pharmaceutical, previously said that the new crown virus may become influenza, and from the history of influenza epidemics, it will not be completely over in one round. Judging from the epidemic situation around the world, the new crown is currently a low-epidemic state. "The first wave of the epidemic in China peaked and passed relatively quickly, and now we also see the opinions of some experts that we may have another wave of the epidemic by May. We are still optimistic about the long-term market value of new crown drugs. ”

In this regard, the above analysts believe that the current clinical demand for new crown virus infection treatment drugs is less, but the new crown virus has not disappeared, although the future is unlikely to be concentrated outbreaks, may be like the flu, scattered existence, so drug reserves are still more important.

"Although 6 new crown oral drugs have been approved for marketing in China, it has to be said that more therapeutic drugs with good efficacy and high safety are still needed clinically." The analyst told the 21st Century Business Herald reporter that I believe that hospitals are now basically able to guarantee medication, which should help to a certain extent. Then the idea of using antiviral drugs should also be opened, some intervention drugs or some of our early drugs, it has a certain effect, we should encourage pharmaceutical companies to develop related drugs. Early intervention is better than late intervention, if there is already white lung or ICU, this time is not only the new crown, even if it is an ordinary disease after entering the ICU, the treatment is relatively difficult.

Source丨21New Health21 original work

Author/Ji Yuanyuan

Editor/Xu Xu

Image/Figureworm