New Corona Therapeutic drugs approved in Japan Summary of the latest situation

As the number of people recuperating at home increases rapidly due to the spread of the new coronavirus, the number of patients who need therapeutic drugs to prevent aggravation is also increasing.

In Japan, currently, all drugs that can be administered in the mild stage are targeted at people who are at risk of severe disease, but what kind of drugs are currently approved in Japan and what effects are there? I have summarized the latest situation.

[What kind of medicine do you have?

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Countries around the world have been developing an oral medicine that is effective shortly after being infected with the new corona, as it can reduce the number of severe cases and deaths.

There are four types of drugs developed for COVID-19, and the currently approved oral drugs in Japan that can be used from the mild stage are

▽ "Lagebrio" developed by Merck, a major American pharmaceutical company, and

▽ American pharmaceuticals. There are two types of "Pakilo Vid Pack" developed by the major "Pfizer".

“Lagebrio” (generic name “molnupiravir”)

On December 24, 2021, “Lagebrio” (generic name: molnupiravir) was the first to receive special approval in Japan.

After the virus invades the cell, it suppresses the action of the enzyme necessary for copying "RNA", which is the blueprint of the virus, and prevents it from multiplying.

According to the package insert of the drug, it is targeted for administration to patients aged 18 and over with mild to moderate disease1 who are at risk of aggravation such as the elderly, obesity, and diabetes, and five days after the onset of symptoms. I plan to take it twice a day for 5 days within the next few days.

Pregnant women and women who may become pregnant should not take this drug as it may affect the fetus.

It is said to have the effect of reducing the risk of hospitalization and death in patients at risk of severe disease by about 30%, and the rate of adverse events after taking the drug is the group who took the drug and the group who took the placebo drug. I assume it hasn't changed.

According to the Ministry of Health, Labor and Welfare, 1.6 million people have been secured so far, and as of July 26, 2022, about 275,100 people have been administered.

"Pakrobid Pack"

Following LaGhebrio, special approval was granted on February 10, 2022 for "Pakilovid Pack" developed by American pharmaceutical giant Pfizer.

It is a drug that combines the antiviral drug 'nilmatrelvir' developed for the new corona and 'ritonavir', which is an existing drug used to treat AIDS and plays a role in enhancing the effect of the antiviral drug.

Like "Lagebrio", it is a type of drug that suppresses the proliferation of viruses that have invaded cells, but the mechanism of action is different. suppress proliferation.

According to the final analysis results of the clinical study published by the company in December 2021, the risk of hospitalization and death was reduced to 89 when administration was started within 3 days of the onset of symptoms for patients at risk of severe disease. 88% reduction even when administration was started within 5 days of onset.

In addition, the rate of adverse events after taking the drug was the same for those who received the drug and those who received the placebo, and most of them were mild.

According to the package insert of the drug, it is to be administered to patients aged 12 years or older with mild to moderate disease 1 who are at high risk of becoming severe, and should be taken twice a day for 5 days.

Pakilovid packs are used because there are about 40 drugs that are prohibited to be taken together, and because doses need to be adjusted for patients with impaired kidney function. The number of cases remains relatively low.

According to the Ministry of Health, Labor and Welfare, 2 million people have been secured, but as of July 26, 2022, about 17,600 people have been administered, which is less than 1/15 of "Lagebrio". .

Both “Lagebrio” and “Pakilovidpak” are believed to have little effect even if the “spike protein”, which is a stepping stone for virus infection of cells, mutates, and the effect is maintained.

Tsuneo Morishima, a visiting professor at Aichi Medical University who is familiar with the treatment of the new coronavirus, said, "Oral medicines are not sufficiently effective unless they are taken quickly, but many people are visiting fever outpatient clinics and patients who need medicine. There are many medicines that can't be taken together with "Pakirovid Pack", but you can ask for information in your medicine notebook or get a prescription at your family medical institution. If the system is in place, we may be able to prescribe more."

[Which medicine can anyone take?

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If a highly effective drug that can be taken by people who are not at risk of becoming seriously ill becomes available, it is believed that the spread of infection may be suppressed and it may be possible to respond to the flu.

"Zokoba"

Japanese pharmaceutical company Shionogi & Co. has applied for approval of its antiviral drug Zokova as a treatment for the new coronavirus, which can be taken at a mild stage even for people who are not at risk of becoming seriously ill.

This drug blocks enzymes that prepare the virus for copying RNA after it has entered the cell.

It suppresses the growth of viruses with the same mechanism as "Pakilovid Pack".

In April, the company presented the results of its clinical trials at an international conference on infectious diseases.

According to this, from January to February this year, 428 mild to moderate new corona patients aged 12 to 70 years old were examined, and they received medicine once and three times a day. Afterwards, the five symptoms of cough, sore throat, runny nose, nasal congestion, shortness of breath, and fever were improved compared to the placebo group.

In addition, the percentage of people with infectious virus was reduced by 90% compared to the placebo group, and the time to become virus-negative was shortened by 1 to 2 days. is.

On the other hand, when comparing the 12 symptoms including diarrhea and nausea, which were the initial evaluation items, there was no clear difference compared to the group who took the placebo.

In addition, on July 14, it was announced that the experiment "confirmed that it has high antiviral activity" against Omicron strains "BA.4" and "BA.5".

The efficacy and safety of this drug were reviewed by the Ministry of Health, Labor and Welfare council twice in June and July.

A member of the committee expressed the opinion that ``it is possible to estimate the effect of reducing the viral load and preventing aggravation'', but ``it may affect the fetus, and it is recommended for women who may become pregnant and elderly people with chronic diseases. There was a series of comments that questioned the effectiveness, such as, "Is it really effective for the symptoms of the Omicron strain?"

The deliberation continued without judging whether or not to approve the proposal, stating that ``it is not possible to make a judgment that its effectiveness can be presumed''.

Shionogi & Co. has announced that it will announce the results of the final stage clinical trial by September, and it is expected that the review will be conducted again around autumn.

Expert "If the effect is clear, it can be treated like influenza"

Visiting Professor Morishima of Aichi Medical University said, ``Shionogi's medicine has the advantage that it can be used by people with a low risk of becoming seriously ill. In Japan, about 10% of the population is infected with the flu, and it is inevitable that waves of infections will continue in the future. I can do it."

["Antibody drug" administered by drip or injection for mildly ill patients]

There are two types of "antibody drugs" developed for the new corona that can be used for mild cases.

It is a type of drug that administers an artificially made antibody, which prevents the virus from entering cells by binding to the ``spike protein'', the protrusion on the surface of the new coronavirus.

Antibody cocktail therapy "Lonapreve"

Of these, the antibody cocktail therapy drug Lonapreve, which administers two types of antibodies, received special approval in July 2021 for the first time as a drug that can be used for mild patients.

Administer by infusion or injection.

"Sotrovimab"

In addition, in September 2021, special approval was granted for Sotrovimab, brand name Zebudy, which administers one type of antibody.

Administer by drip.

Patients with mild to severe symptoms of pneumonia, such as the elderly and those with underlying diseases, are eligible for administration, and are administered once within 7 days of onset.

It is also approved to be administered for the purpose of preventing onset to those who have close contact with people who have weakened immunity and are at risk of becoming seriously ill.

In clinical trials, Lonapreve reduced the risk of hospitalization and death by about 70% compared to those who did not receive it.

According to the Ministry of Health, Labor and Welfare, the number of people who have been administered will reach about 40,000 as of July 26, 2022.

In clinical trials, sotrovimab reduced the risk of hospitalization and death by approximately 85% compared to those who did not receive it.

According to the Ministry of Health, Labor and Welfare, as of July 26, 2022, more than 150,000 people have been administered the drug.

However, these antibody drugs have the weakness that if the virus mutates and the shape of the "spike protein" changes, it becomes difficult to bind and the effect decreases.

Especially for Omicron strains, there were many reports that the effect was significantly reduced compared to conventional strains. Therefore, it is considered to be used when other therapeutic agents cannot be used.

[Therapeutic drug developed for another disease for mild patients]

"Remdesivir"

Some drugs have been developed as therapeutic drugs for other diseases and are also used as effective against the new coronavirus, and some of them can be used from the mild stage.

Originally developed as a treatment for Ebola hemorrhagic fever, the infusion antiviral drug `` Remdesivir '' was approved for the first time as a treatment for the new corona in May 2020.

It has been used for severe hospitalized patients from the new corona moderate disease 1, but in March 2022, the Ministry of Health, Labor and Welfare expanded the indication to mild and moderate patients who are at risk of becoming severe.

Medications for patients with moderate disease 2 or higher

For moderately ill patients who developed pneumonia and required oxygen administration, and for severely ill patients with more severe symptoms, drugs that suppress the excessive action of the immune system are available to suppress inflammation in various parts of the body. used.

"Dexamethasone"

In July 2020, the Ministry of Health, Labor and Welfare recommended ``Dexamethasone'', a steroid that suppresses the excessive action of the immune system, as a treatment for the new corona.

It was originally used to treat severe pneumonia and rheumatoid arthritis.

"Baricitinib"

Baricitinib, which was approved in April 2021, is also a drug that suppresses excessive immune activity and is administered to patients with moderate disease 2 or higher.

Originally, it was an oral tablet that was used for patients with rheumatoid arthritis, etc. In Japan, it is limited to use in combination with remdesivir.

"Actemra"

The rheumatoid arthritis drug Actemra, generic name Tocilizumab, developed by the Japanese pharmaceutical company Chugai Pharmaceutical, was approved in January 2022 as a treatment for the novel coronavirus.

It is a drug that suppresses excessive immune function by intravenous drip, and it is said to be administered in combination with steroids to patients with moderate disease 2 or higher who need oxygen administration.