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Not long ago, the news that a drug could reduce the hospitalization or death rate of people infected with the new crown by 50% attracted much attention as soon as it was disclosed, and even caused the overall stock market to fluctuate.
As soon as a paper entitled "The Latest Research Progress of Clinical Treatment Drugs for Novel Coronavirus Pneumonia" was published in the "Chinese Journal of New Drugs", it has been downloaded more than a thousand times.
At the Fifth China Innovative Drug Forum held on October 23, the conference announced relevant papers and data in academic journals.
Shi Shengyi, deputy general manager of China National Pharmaceutical Group Co., Ltd. and executive editor of "China New Drug Journal", said at the meeting that the magazine had planned a new coronavirus drug research column, and industry experts produced relevant research results in a short period of time and responded positively.
Many industry experts said in their speeches that finding effective drugs for the treatment of new coronary pneumonia is one of the main points of force in the current medical research and development field.
The new crown virus has mutated several times and is prevalent in many countries. The trend of the new crown epidemic is currently difficult to predict. “Delta mutant strains are circulating in more than 150 countries. Afterwards, the Namda mutant strain spread to more than 30 countries, and the Miu mutant strain appeared in more than 50 countries.” said Chen Zhinan, academician of the Chinese Academy of Engineering and professor at the Air Force Military Medical University. While achieving effective prevention and control, the demand for effective drugs for the new coronavirus has also become more and more urgent.
This coincides with the views of Chen Kaixian, academician of the Chinese Academy of Sciences, at another academic conference a few days ago. Chen Kaixian said: The mutant strains have a strong spreading power, and in many countries and regions with a certain coverage of vaccination, they still cause new problems. A round of epidemics. This highlights the importance and urgency of the research and development of specific anti-coronary pneumonia drugs.
So, how to find effective drugs for the new crown pneumonia virus? Can a drug be found to be as effective against the new coronavirus as artemisinin is against the malaria parasite?
In fact, since the new crown pneumonia epidemic, China's medical field has developed a R&D layout in many fields such as new use of old drugs, traditional Chinese medicine, innovative biological drugs, and antibody drugs. Authoritative data shows that in China, 31 drugs have entered clinical trials in the new coronary pneumonia drugs. The "three medicines and three prescriptions" that performed well in the Wuhan epidemic have all been approved for listing.
"On November 13 last year, Mepezumab was approved by the U.S. FDA to initiate an international multi-center phase III clinical study. The first phase of enrollment treatment of 176 critically ill patients has been completed, waiting to be unblinded." At the meeting, the latest clinical research progress of the original innovative drug for new coronary pneumonia developed by his team was shared.
Not only has it gained international recognition, since July 2021, Mepezumab has also been used in the treatment of patients with new coronary pneumonia in Shanghai, Shenzhen, Chengdu, Guangzhou and other places in China.
From target discovery, infection path mechanism analysis to antibody drug research and development, this innovative drug was independently completed by the Chinese R&D team from its birth to its landing.
"In March and April last year, our laboratory was reported to have discovered that CD147 is an important receptor that mediates viral infection. This was the first discovery in our laboratory." Chen Zhinan said.
In other words, the new crown virus uses the "key" to open more than one "lock" on human cells, in addition to the generally recognized ACE II, there is also CD147. Based on this breakthrough in basic research, the team completed the design and verification of antibody drugs in one go, and industrialized them into the drug landing.
Whether these original innovative drugs will become a killer for the treatment of new coronary pneumonia is waiting for further data disclosure.
The reporter learned from the meeting that chemical drugs and neutralizing antibody drugs that have clinical value against the new coronavirus variant strain will enter a special approval process.
"On the basis of the daily urgent need for drug review and approval, our next step is to focus on new crown drugs as a key breakthrough direction." Kong Fanpu, director of the Center for Drug Evaluation of the National Medical Products Administration, said at the meeting that we will advance the emergency review of anti-epidemic drugs. The review is normalized, and relevant departments will adjust the range of special approval procedures to speed up the review and approval of new coronary pneumonia therapeutic drugs.
The world's first oral drug for the new crown has been "an arrow on the string", and clinical trials have shown that it can reduce the hospitalization rate by 50%
On October 11, Merck & Co. (hereinafter referred to as MSD) announced that it had submitted an emergency use authorization application for the drug monupivir (English name Molnupiravir) to the U.S. Food and Drug Administration (FDA). In addition, Merck is submitting applications to regulatory agencies in other countries around the world.
Monupivir is an oral antiviral drug used to treat adult patients with mild to moderate new coronary pneumonia at risk of exposure. The interim results of the Phase III clinical trial showed that the drug reduced the risk of hospitalization or death of patients by approximately 50%.
It is worth noting that even if it has not yet been approved, monupivir has been ordered for 1.7 million treatment courses (worth US$1.2 billion). In addition, Merck has signed supply and purchase agreements for monupivir with governments of many countries around the world, and it is now in the stage of waiting for authorization.
Convenient administration, low cost and easy production
Monupivir is an oral ribonucleoside analog, developed by Merck and another biotechnology company called Ridgeback, which can inhibit the replication of a variety of RNA viruses, including the new coronavirus. If approved, it is expected to become the first oral antiviral drug for the treatment of new coronary pneumonia.
In fact, monupivir is not a new drug. It has been used to treat influenza and other diseases before. Later, it was found to be effective against SARS and other coronaviruses in research, and it became a new crown specific drug.
From the principle point of view, monupivir induces mismatch mutations in the process of RNA replication, thereby inhibiting the generation of functional viruses in the offspring. Simply put, it can integrate itself into the genetic material of the virus, and then cause a large number of mutations when the virus replicates, thereby effectively "killing" the virus. Compared with injectable drugs, this oral drug has the advantages of convenient administration, low cost, and easy expansion of production.
Wang Jinglan, chief physician of the Department of Respiratory and Critical Care Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, told China News Weekly that, overall, the emergence of new crown oral drugs is good news, which means that there will be an additional "weapon" in treatment in the future. He believes that whether monupivir will enter the hospital and be used on patients in the future depends on the specific efficacy and safety data of the drug, such as pharmacology, toxicology and clinical data.
The interim results of the Phase III clinical trial published by Merck showed that among the patients who took monupivir 2 times a day 4 capsules once a day for 5 consecutive days after a 29-day follow-up, the hospitalization rate was 7.3%, and there were no deaths; Among patients treated with placebo, 14.1% were hospitalized or died, and 8 of them died.
In terms of effectiveness, monupivir reduces the risk of hospitalization or death by approximately 50%. In addition, monupivir has shown consistent efficacy in different new coronavirus variants, including the delta mutant and the Miu mutant.
Based on this positive data, Merck submitted an emergency use authorization application to the FDA on October 11. If the drug is approved, the U.S. government will purchase 1.7 million courses of drugs worth 1.2 billion U.S. dollars (approximately 7.7 billion yuan). At the same time, Merck has signed monupivir supply and pre-purchase agreements with governments of many countries or regions around the world.
According to Merck’s estimates, 10 million treatment courses of monupivir will be produced by the end of 2021.
Jin Dongyan, a virology expert at the University of Hong Kong, said in an interview with China News Weekly that this oral medicine is still effective and helps reduce the rate of hospitalization and severe illness. But he emphasized that it is impossible to control the epidemic through oral medication alone.
"This drug is mainly useful for patients in the early stage of the onset of the new crown. For those patients who have been infected for a long time or have even developed severe illness, the efficiency will be greatly reduced." Jin Dongyan pointed out that to really control the epidemic, we still need to rely on vaccines. , The special effect medicine can only play a certain supporting role.
German Chinese virologist and Professor Lu Mengji from the Institute of Virology at the University of Essen School of Medicine told China News Weekly that a high-level immune barrier still needs to be established in the entire population at this stage. Although new crown oral drugs can have a certain therapeutic effect, small-molecule drugs cannot completely kill the virus, and the ultimate cure depends on the own immune system.
In his view, the best way to protect is to allow the immune system to form a long-term memory of the virus, so vaccines are the most effective way to fight the virus. Some people whose own immune system is not working properly can try to use the new crown oral medicine, which can reduce hospitalization or death to a certain extent, but this part of the population is after all a minority.
It can reduce the risk of hospitalization or death by half, and has the advantage of oral administration. Monupivir is undoubtedly a "dazzling" presence in the new crown drug, and it was also dubbed the "new crown drug", which once caused stock price shocks.
On the day when Monupivir’s Phase III clinical data was announced (October 1), Merck’s stock price rose by more than 12% during the intraday session, the highest intraday gain since 2009, with a closing gain of 8.37%. The new crown vaccine, antibody therapy, New crown concept stocks such as other oral drugs fell sharply.
"Vaccines and specific medicines are themselves competing with each other, one ebb and flow." Shi Lichen, a medical strategy expert, said that the new crown oral medicine is the right medicine, and the future market is still worth looking forward to.
However, while arousing widespread concern in the industry, this "new crown magic drug" is also facing many controversies, involving long-term security risks, high prices and many other issues.
In the interim results of the Phase III clinical trial announced by Merck, the data of 775 patients were finally included in the evaluation, of which only more than 300 people actually received monupivir treatment. The incidence of all adverse events was similar in the monupivir group and the placebo group (35% and 40%, respectively). Similarly, the incidence of drug-related adverse events is also comparable (12% and 11%, respectively).
Lu Mengji said that monupivir can induce base mismatches, and there is a risk of mutagenesis, which may affect the function of the body's own genome. Because a course of treatment is only 5 days and the observation time is limited, it is unclear whether there will be long-term effects such as carcinogenicity in the future.
He believes that although monupivir can be taken orally, infected persons belonging to high-risk groups still have a 50% chance of becoming severely ill after taking the drug. Therefore, high-risk patients still need to seek medical observation, and the pressure of medical services still exists. In addition, this drug mainly works on people with early new crown infections. Most people are unlikely to have a nucleic acid test every 3-5 days and be treated in time after the test is positive. From this perspective, this medicine also has limitations in its use.
Jin Dongyan believes that the safety of new crown oral drugs is still acceptable. Because nucleoside analog drugs have been widely used in the treatment of AIDS, influenza and other diseases in recent years, the overall risk is not high. However, he also emphasized that if this drug can be popularized in the future, whether people will cause drug resistance after large-scale use is still unknown, and we need to be vigilant.
Based on the information disclosed by Merck, the price of this drug for a course of treatment (5 days) is about US$700, and the production cost is only US$17.44. The price of the drug is more than 40 times the cost, which is a huge difference. Because of its high price, monupivir is also known as one of the most profitable drugs in history.
Shi Lichen believes that a drug needs to be cost-sharing from R&D to market, and the price is reasonable. He believes that from this perspective, a 5-day treatment course of US$700 is not particularly expensive.
In Jin Dongyan's view, monupivir is expensive, making it impractical to use it as a home-stock medicine. He believes that when the vaccine is effective, the space for oral drugs to control the new crown infection is actually relatively limited. Because most people who have been vaccinated are mild or asymptomatic people, it is not necessary to take this medicine.
Despite the controversy, it has not hindered the "hot" pace of monupivir, and has triggered panic buying in many countries before it has been approved. According to estimates by Airfinity, a scientific data analysis company, about 10 countries or regions have signed agreements or are negotiating with Merck.
Jin Dongyan pointed out that there will definitely be more similar drugs in the future, and there will be more clinically available programs than currently available.
The success of monupivir ignited the market's enthusiasm for oral antiviral small molecule drugs. In addition to monupivir, there are currently a number of oral small molecule antiviral drug candidates in phase III clinical phases around the world, including pioneering pharmaceutical industry's androgen receptor antagonist procrulamide, and Pfizer's 3CL protease inhibitor PF- 07321332 and so on.
However, the R&D process is also accompanied by uncertain risks. According to reports, on October 19, Roche/Atea announced that the phase II clinical study of its new crown oral drug AT-527 had failed. Affected by this news, Atea's stock price plummeted, with a market value of less than $1 billion.
It is worth noting that the new crown oral medicine is a therapeutic drug, that is, it is used only when it is infected with new crown pneumonia. Lu Mengji said that current prevention is the most important thing, so we must vigorously promote vaccination to prevent infection.
Some analysts also believe that although the new crown oral drug "adds bricks" to the anti-epidemic, the current "vaccine + specific drug" is still the best combination of prevention and treatment. The two are not a simple alternative relationship, and the impact of the new crown drug should be viewed objectively.
