Text | Wu Ni
Edit | Yang Zhongxu
Cartography | Li Ziya
Driven by the huge market demand, the new crown oral medicine has become a popular track, bringing great increments to the upstream API industry, the small molecule CDMO industry, and the downstream circulation industry. As the only conditionally approved COVID-19 oral drug in the Chinese mainland, every action of Pfizer Paxlovid has attracted much attention.
In February, CXO companies 002821.SZ and 300363.SZ signed large orders one after another, and the market predicted that it was an order for Pfizer's new crown oral drug, and its stock price rose sharply.
The latest week about China Pharmaceutical and Health Industry Co., Ltd. (600056. SH) (hereinafter referred to as "China Pharmaceutical") and Pfizer reached a cooperation on the new crown oral drug, so that China Pharmaceutical for 4 consecutive trading days.
On March 9, the cooperation between China Pharmaceutical and Pfizer finally surfaced. China Pharmaceutical announced that it has signed an agreement with Pfizer to be responsible for Paxlovid's commercial operations in the Chinese mainland market during the agreement period (FY2022).
Paxlovid's advances in commercialization have brought patients one step closer to innovative therapeutics. At a time when the number of new confirmed cases in the country is on the rise, this is undoubtedly good news.
Since the outbreak of the new crown epidemic, the prevention and control system of the Chinese mainland has adhered to the principle of "prevention first, prevention and control combined". Oral COVID-19 drugs are expected to fill the treatment gap that reduces the risk of severe illness and are seen as the last "puzzle" of prevention and treatment integration.
Now that the puzzle has been assembled, can the COVID-19 prevention and control policy open the next stage?
01 Wait for the medicine to come
The Olmikeron mutant strain has replaced Delta as the world's leading epidemic strain. One of the challenges that has to be faced is that the existing inactivated vaccines have reduced their ability to prevent Ami kerong compared to Delta.
Covid-19 therapeutics are expected to be high. "Imagining the COVID-19 pandemic as a flood, vaccines act as shore guardrails and don't let people fall into the water is the best way to do it." Unfortunately, what to do if someone falls into the water, put down the life jacket to save people, this is the role of the new crown special drug. Xu Fujie, a former professor at the First Affiliated Hospital of Zhejiang University, said in an interview with the media.
The two big fists of COVID-19 therapeutic drugs are neutralizing antibodies and small molecule oral drugs. In simple terms, the role of neutralizing antibodies is to block the infection of human cells by the new crown virus, and the role of small molecule oral drugs is to block the replication and proliferation of the new crown virus. The two treat the new crown in layers, and jointly build a prevention and control system with the new crown vaccine.
The advantages of oral medicines are that they are easy to use and patient compliance, and pricing is more advantageous, such as Merck Mornaupiravir, which is priced at about one-third of the cost of neutralizing antibody therapy. It can play an important role in large-scale outbreak control, so it has attracted much attention.
However, due to the difficulty of research and development, the progress of small molecule oral drugs is slightly bumpy. Even roche, an established pharmaceutical company, has struggled in this area — the AT-527 oral COVID-19 drug developed by Roche and partner Atea failed to pass mid-term testing. The last two new drugs are Merck's Molnupiravir and Pfizer's Paxlovid.
Paxlovid is undoubtedly more eye-catching. Clinical trial data released by Pfizer in December 2021 showed that the drug was 89% effective in preventing hospitalizations and deaths in patients at high risk for severe illness. This data is significantly better than Merck's 50% of Molnupiravir and better than some current clinical data on COVID-19 neutralizing antibodies.
From the results of the interim analysis, the safety of the oral agent is good. The safety data of 1881 patients published showed that the rate of adverse events in the drug and placebo groups, 19% and 20%, respectively, was not significantly different, and most of them were mild adverse events. Other drug contraindications require more detailed disclosure of clinical trial data, even in conjunction with long-term follow-up investigations.
Paxlovid has been recognized as an important tool for global epidemic prevention and control. From December 2021, Paxlovid has been approved for use in the United States, Israel, Canada, Europe and Japan. On February 11 this year, the NmPA conditionally approved Paxlovid to be listed on Chinese mainland, just 50 days after the U.S. Food and Drug Administration (FDA) emergency use authorization.
So far, Chinese mainland has gathered an effective combination of covid-19 vaccines, neutralizing antibodies and small molecule oral drugs to fight the epidemic.
In the face of paxlovid drug resistance, industry insiders have different views. Some researchers and drugmakers say the covid-19 drug is only taken for 5 days, which is too short a time and the risk of developing resistance is low. John Mellors, an infectious disease expert at the University of Pittsburgh, believes that drug resistance is almost an inevitable consequence.
Fortunately, the next new crown oral drug has been "arrow on the string". Japan's fifth-largest pharmaceutical company, Yoshinori Shiono Pharmaceutical, is applying for a license to produce and sell oral drugs for the new crown virus. If approved, an additional COVID-19 oral drug will be added. In addition, Junshi Bio's small molecule oral drug VV116 has been approved for use in Uzbekistan, and has entered the phase III clinical trial stage in China, which is expected to become the first domestic new crown oral drug in mainland China. The "COVID-19 puzzle" is getting closer and closer.
02 The transition of epidemic prevention from "prevention-oriented" to "treatment-oriented"?
People who are looking forward to oral COVID-19 drugs may ask: Can oral drugs replace vaccines?
The current consensus is no. Zhou Yebin, a doctor of genetics engaged in the research and development of tumor immune drugs, said, "Even if oral antiviral drugs are important, their role is not to replace vaccines, but to supplement the existing vaccine-based epidemic prevention measures." ”
The current outbreak in Hong Kong has unfortunately confirmed this.
According to the latest news from the Hong Kong Government News Network, as of 00:00 on March 9, there were 25,991 new confirmed cases of new coronary pneumonia in Hong Kong, of which 25,984 were local cases. So far, the fifth wave of the epidemic in Hong Kong has accumulated 538602 confirmed cases after nucleic acid testing, with a total of 2656 deaths, with a case fatality rate of 0.46%.
One of the main reasons for Hong Kong's high case fatality rate is the low vaccination rate. Hong Kong's vaccination rate is 74%, and only 66% of the two doses of the vaccine are vaccinated. Vaccination rates are even lower among older adults – 55.06% of people aged 70-79 have completed two doses of vaccination, while in people aged 80 years or older, the vaccination rate is only 26.26%.
Data from the UK Health Security Agency show that in people infected with Omicron, if completely unvaccinated, the case fatality rate is 8% for 70-79 years old and as high as 21.3% for people over 80 years old.
Although Merck's Molnupiravir has been used in Public Hospitals in Hong Kong, oral medicines are difficult to turn the tide as a "remedy" after infection, and the effect is not obvious at present.
The status of vaccines cannot be shaken. But the combination of high vaccination rates and efficient oral COVID-19 drugs has made public policies for COVID-19 prevention and control more possible. For example, the focus of epidemic prevention has been transitioned from "prevention first" to "treatment first".
Chinese mainland economy with the lowest number of COVID-19 patients and the lowest mortality rate in the world, with a prevalence rate of 8.9 per 100,000 and a mortality rate of 0.4 per 100,000. Xiang Dong, deputy director of the Research Office of the State Council, said that the full vaccination rate of the new crown vaccine in Chinese mainland has exceeded 87% by the end of February 2022. Building on these prevention gains, the pressure left for the last floodgates of COVID-19 oral medicines is relatively small. The effectiveness and safety of Paxlovid is expected to make the treatment of the new crown as convenient as the treatment of the flu, allowing most people with mild and moderate illness to cure themselves at home.
If this approach is feasible, the consequent impact is that ORAL COVID-19 drugs are widely available as a family treatment method, effectively reducing the pressure on medical resources and reducing the cost of social fight against the epidemic.
This is the case in Singapore, which calls on most non-critically ill patients not to go to the hospital, stay at home, and recover at home. From the first confirmed case of COVID-19 in Olmikron on 6 January 2022 to 7 March 2022, there were more than 560,000 confirmed cases in singapore, including 250 deaths, and the case fatality rate remained at 0.044%.
Notably, Singapore's vaccination rate is as high as 91%, of which 88% of the two doses of vaccine are vaccinated.
How to adjust the retraction needs to be carefully considered. If the transition from "prevention-oriented" to "treatment-oriented" Chinese mainland vaccination rates may be further increased, minimizing the pressure left for oral COVID-19 drugs.
(The author is a researcher of Caijing)
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Resources
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[2] When will the antiviral drugs often available at home be realized? Ding Sheng, Dean of school of pharmacy at Tsinghua University, The Paper, 2021
[3] "Miracle Drug" Worries: Will the New Coronavirus Evolve "Drug Resistance", Wall Street Insights, 2022
[4] In-depth | China's NEW CROWN Special Drug R&D Sprint: Key Progress Revealed in the Industry, Zhongxin Jingwei, 2021
[5] The two big fists of the new crown treatment drugs are neutralizing antibodies and small molecule oral drugs. In simple terms, the role of neutralizing antibodies is to block the infection of human cells by the new crown virus, Singularity Network, 2022
[6] Ten questions and ten answers| Pfizer launched the "new crown oral special drug", which is more effective than the vaccine, Gan Wei, 2021
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