Author丨Ji Yuanyuan
Editor丨Xu Xu
Picture Source丨Tu Chong
On the last working day of 2022, the country ushered in the approval of the third oral drug for COVID-19.
On December 30, the official website of the State Food and Drug Administration announced that in accordance with the relevant provisions of the Drug Administration Law, the State Food and Drug Administration conducted emergency review and approval in accordance with the special drug approval procedures, and conditionally approved the import registration of Merck's new coronavirus treatment drug Monolavir Capsules (trade name: LAGEVRIO).
Monolavir is an oral small molecule novel coronavirus treatment drug. It is used to treat adult patients with mild to moderate novel coronavirus infection (COVID-19) who have high risk factors for progression to severe disease, such as patients with advanced age, obesity or overweight, chronic kidney disease, diabetes, severe cardiovascular disease, chronic obstructive pulmonary disease, active cancer and other high risk factors for severe disease. Patients should take the medication strictly according to the instructions under the guidance of a physician.
According to Merck official information, monogravir is the world's first approved oral anti-COVID-19 drug. It has currently obtained marketing approval or emergency use authorization in more than 40 countries or regions, including the United States, EU , the United Kingdom, Australia, Japan, South Korea, Hong Kong, China, Taiwan, etc. As of December 2022, Merck has supplied more than 9 million courses of monogravir globally, treating approximately 2.7 million patients infected with the new coronavirus. Currently, the exclusive domestic importer of Merck’s COVID-19 oral medicine is Sinopharm. In September 2022, Merck signed a cooperation framework agreement with Sinopharm, granting the distribution rights and exclusive import rights of monogravir in China to Sinopharm. In November 2022, Merck signed a distribution agreement with Sinopharm Holdings Distribution Center Co., Ltd. on the import and distribution of monogravir in China.
In addition, the domestic commercial pricing of the drug has not yet been determined. It costs US$700 per course of treatment in the US market, which is higher than the government procurement price of Pfizer's new coronavirus oral drug (approximately US$530 per course of treatment). "As to whether and when monogravir will be included in the national medical insurance catalog, please refer to the public information released by the government. We are maintaining active communication with relevant departments and hope that monogravir can benefit Chinese patients as soon as possible." Merck said to 21 Century Economic Report .
How effective is Merck’s oral COVID-19 drug?
Monolavir is an oral ribonucleoside analogue under investigation that can inhibit the replication of SARS-CoV-2 (the causative factor of the new coronavirus). It is jointly developed by Merck and Ridgeback. This drug is the world’s first approved oral anti-new coronavirus drug. , Monolavir was conditionally approved for marketing by the British Medicines and Healthcare Products Regulatory Agency (MHRA) in November 2021, and in December 2021, it received emergency use authorization from the US Food and Drug Administration (FDA) and emergency special approval from the Japanese Ministry of Health, Labor and Welfare. In December 2021, the results of the MOVe-OUT Phase 3 clinical trial of the drug showed that early treatment with monogravir can significantly reduce the risk of hospitalization or death in unvaccinated high-risk adult patients with COVID-19.
Based on the Phase 3 MOVe-OUT clinical trial of monogravir, which evaluated 800 mg doses of monogravir twice daily in non-vaccinated, non-hospitalized adult patients with laboratory-confirmed mild to moderate COVID-19 who developed symptoms within five days before randomization in the study and who had at least one risk factor associated with poor disease outcome (e.g., heart disease, diabetes).
In an analysis based on all randomized patients (n=1433), monogravir reduced the risk of hospitalization or death: 9.7% (68/699) of patients in the placebo group were hospitalized or died, and 6.8% (48/709) of patients taking monogravir were hospitalized, for an absolute risk reduction of 3.0% (95% confidence interval [CI]: 0.1, 5.9). Nine deaths were reported in the placebo group and one death was reported in the monogravir group. Determination of primary effectiveness of
was based on a planned interim analysis of 762 subjects. In this interim analysis, treatment with monogravir significantly reduced the number of hospitalizations or deaths from randomization to day 29: 14.1% (53/377) of patients in the placebo group were hospitalized or died compared with 7.3% (28/385) of patients in the monogravir group, for an absolute risk reduction of 6.8 percentage points between the monogravir and placebo groups (95% confidence interval: 2.4, 11.3; P=0.0024).
In clinical studies, the most common adverse reactions were diarrhea, nausea and dizziness. One percent of subjects taking monogravir and 3% of those taking placebo discontinued due to an adverse event (AE). Serious adverse events occurred in 7% of subjects taking monogravir and 10% of subjects taking placebo; most serious adverse events were related to COVID-19. In this regard, a securities analyst in the pharmaceutical industry told a reporter from the 21st Century Business Herald that monogravir is a nucleoside analogue, which is an RdRp inhibitor in terms of its therapeutic mechanism. Drugs that also belong to this category of inhibitors include Real Biotechnology's Azivudine, Junshi Biotechnology's VV116, etc. Unlike Pfizer's oral drug Paxlovid, which has a different target entry point, monogravir's RdRp mechanism drug is different from 3CL in its blocking mechanism. As for the future market application prospects of drugs with two mechanisms, they need to be comprehensively evaluated in terms of safety and effectiveness.
RdRp is an RNA-dependent RNA polymerase. RdRp plays an important role in the replication process of virus . It is an essential and most conserved protein of RNA virus , and this enzyme does not exist in normal host cells. Inhibition of RdRp can effectively achieve anti-RNA virus effects, and it is its similarity to the structure of nucleotide that provides certain broad-spectrum antiviral properties.
MSD told reporters from the 21st Century Business Herald that in terms of the course of treatment, foreigners need to take 4 pills at a time, twice a day, and a course of treatment every 5 days. As for when it will officially enter clinical application in China, there is currently no clear time.
"However, it can be seen from the previous clinical data of monogravir that this drug may have reactions including diarrhea, nausea and dizziness. Therefore, it needs to be emphasized that the use of new coronavirus drugs cannot be rushed and needs to be treated with caution. Patients are not allowed to use the drug without authorization before using the drug. They need to consult a professional pharmacist and follow the doctor's instructions. If monogravir wants to open the domestic market, it also needs to withstand many tests to gain widespread recognition from society." The above-mentioned analyst said. Wang Wenhua, a partner of
CIC Consulting, told the 21st Century Business Herald reporter that this time Monolavir was approved for marketing with conditions, and the so-called conditional approval means that people who take the drug need to strictly follow the doctor's orders and drug instructions.
How big is the competitive space in the Monoravir market?
At present, most of the new coronavirus infections show mild or asymptomatic symptoms, but there are still a few infected people who show pneumonia , especially the elderly with underlying diseases and those who have not been vaccinated. These groups are at high risk of severe illness. To provide early intervention for these people at high risk of severe disease, the ninth edition of the diagnosis and treatment plan recommends several antiviral drugs, including monoclonal antibodies, Pfizer's oral COVID-19 drug and the domestic COVID-19 oral drug Azivudine. Early use of these antiviral drugs may reduce the occurrence of severe illness, shorten the course of the disease, and shorten the shedding time of the virus.
This time, the launch of Monoravir is considered by the industry to be a necessary action in response to the epidemic. This time, the indication of monogravir is to treat adult patients with mild to moderate novel coronavirus infection (COVID-19) who have high risk factors for progression to severe disease, such as patients with advanced age, obesity or overweight, chronic kidney disease, diabetes, severe cardiovascular disease, chronic obstructive pulmonary disease, active cancer and other high risk factors for severe disease. This also means that reducing the risk of death for severely ill patients has become a major direction that the country is currently focusing on.
A virus expert told a reporter from the 21st Century Business Herald that the three-year outbreak of the new crown epidemic has given us a better understanding of this disease.With this understanding of , our prevention and control strategies have actually made great adjustments. In the past, it was to prevent the spread of the disease and prevent the spread of the disease. Now the focus of protection is not to prevent infection, but to prevent severe disease and prevent serious harm caused by the disease. At this point, our prevention and control strategies, work priorities, and focus have also been adjusted accordingly. Therefore, we will devote more energy to severely ill patients and elderly and vulnerable groups.
"From the perspective of clinical experience, early use of antiviral drugs must be effective. As long as the mechanism and efficacy of the drug are consistent with the antiviral effect, there should be no problems. Of course, in terms of the applicable population of the drug, the drug is currently approved for patients with high risk factors for severe disease, but the specific medication needs to be judged by the doctor based on the patient's condition. As an antiviral drug, it is very meaningful to reduce the viral load early, and the specific medication needs to follow the doctor's advice." The virus expert said.
Professor Sheng Jifang, director of the Department of Infectious Diseases at the First Affiliated Hospital of Zhejiang University School of Medicine, said that the currently circulating new coronavirus Omicron variant strain has strong immune evasion ability and a low risk of severe illness and death after infection. However, factors such as those who have not completed basic vaccine immunity or enhanced immunity , the elderly, and those with combined chronic diseases are still important risk factors for the development of severe illness and death after infection with Omicron. Early use of effective antiviral treatment drugs will help to clear and improve symptoms earlier, clear the virus quickly, and reduce the risk of hospitalization or death. Patients with underlying diseases, especially those with impaired liver or kidney function, also need to pay attention to the interactions between various drugs, use drugs rationally according to doctor's instructions, and be the first guardian of their own health. Regarding the layout of
in the domestic market, Merck has also been preparing for the commercialization of Monoravir early on. At the commercialization level, in September 2022, Merck signed a cooperation framework agreement with Sinopharm, granting the distribution rights and exclusive import rights of monogravir in China to Sinopharm. In November 2022, Merck signed a distribution agreement with Sinopharm Holdings Distribution Center Co., Ltd. on the import and distribution of monogravir in China.
In terms of pricing, according to public information, the price of monogravir in the United States is US$700 for a course of treatment, which is approximately RMB 5,000. Currently, the adjusted domestic medical insurance payment price of Pfizer's COVID-19 oral drug Paxlovid is 1,890 yuan/box, which is even higher than Azivudine's online medical insurance price of 270 yuan/bottle.
Regarding the domestic pricing of monogravir and whether it will be included in medical insurance, a reporter from the 21st Century Business Herald consulted a relevant person from Merck. The person said that globally, Merck is committed to accelerating the widespread, fair and affordable patient access of monogravir after authorization or approval; in China, this commitment remains unchanged. We conduct tiered pricing based on the World Bank's classification of countries' financing capabilities to respond to the pandemic. This pricing framework is designed to enable patients to quickly obtain monogravir. We are confident in the clinical performance of monogravir and believe that this drug has the potential to bring significant benefits to patients and add value to the healthcare system.
"As to whether and when monogravir will be included in the national medical insurance catalog, please refer to the public information released by the government. We are maintaining active communication with relevant departments and hope that monogravir can benefit Chinese patients as soon as possible." Merck said.
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Editor of this issue Jiang Peipei Intern Wu Ziying
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