COVID-19 oral drug clinical trials in full swing

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The race to develop oral drugs to treat mild COVID-19 infections is in full swing. With the number of new infections oscillating in waves between lows and highs (sometimes exceeding 10,000 per day), the development of effective therapeutic drugs, beyond vaccines, is essential to bring the pandemic under control.

In particular, an oral medication that can be taken as a cold medicine in the early stages of infection could not only prevent infected people from developing severe symptoms, but also reduce the burden on healthcare facilities.

Several new drugs are in clinical trials in Japan and around the world, and some have reached the final stages before commercialization.

Prevention of severe cases, spread of infection

Drugs currently approved in Japan for the treatment of COVID-19 include the following drugs:

• Remdesivir, an antiviral drug;
• Dexamethasone, which suppresses excessive immune and inflammatory responses;
• Baricitinib, which also suppresses excessive immune and inflammatory responses;
• The “antibody cocktail“of Casirivimab and Imdevimab developed specifically for COVID-19.

The “antibody cocktail” received special approval for use in Japan in July 2021 and is also indicated for patients with mild cases. The range of patients eligible to receive the drug was expanded to include outpatients in August to cope with the growing number of people recovering at home.

Unlike other approved drugs, expectations for this drug are particularly high because it is the first drug for patients with mild infections. However, since it is an intravenous medication, it cannot currently be used at home.

Oral medications

The biggest advantage of the oral antiviral drugs currently in development is that they are easy to use and can specifically target the early stages of infection when the virus is multiplying. If asymptomatic or mildly ill patients who recover at home could take such a drug immediately after infection was detected, it could not only prevent the development of serious disease, but also stop the spread of infection.

Additionally, these drugs have the potential to provide some relief to overwhelmed healthcare facilities facing a shortage of hospital beds.

In addition, since the surface proteins of the virus, which are targeted by the antibodies produced by vaccines, are subject to mutation, some have pointed out the potential for loss of efficacy of vaccines. However, the oral drugs under development act on another part of the virus and are therefore less affected by the various mutations that have been confirmed to date.

New options for 3 pillars: prevention, diagnosis, treatment

The main types of oral medications that many companies are currently developing are:

• Molnupiravir, developed by the American pharmaceutical giant Merck;
• AT-527, developed by the Swiss pharmaceutical giant Roche.

Both of these drugs are RNA polymerase inhibitors that prevent viruses that have entered cells from replicating their genes. They work on the basis of the same mechanism as Remdesivir and Fujifilm Toyama Chemical’s influenza drug, Avigan.

A joint international clinical trial involving a large group of patients, including Japanese patients, has entered its final stages.

According to MSD KK, the Japanese subsidiary of Merck, Molnupiravir will be tested on ambulatory patients in the early stages of infection with symptoms such as fever and cough. Patients will take the medicine twice a day for five days, and its effectiveness will be compared to that of patients given a placebo. Final data should be available by October.

The company aims to submit an emergency use authorization application in the United States by the end of 2021, and it plans to submit an application for approval in Japan soon after.

According to Chugai Pharmaceutical, a subsidiary of Roche, AT-527 was originally developed to treat hepatitis C infections. Now, however, it is being tested in patients with mild to moderate cases of COVID-19. An interim analysis of clinical trials showed that in a comparison of patients with moderate cases who received the drug and those who received a placebo, the drug was effective in reducing the virus by an average of 80% on the second day of treatment.

Final clinical trial results are expected within the year, and Chugai aims to file for approval in Japan in 2022. At a press conference on August 26, Chugai’s project manager Masaya Seki said Says: “It is extremely important that this oral medication prevents mild infections from becoming serious. We will do our best to increase the production volume.

• The American pharmaceutical giant Pfizer is also developing an oral drug, PF-07321332.

The medicine is a type called a protease inhibitor, which prevents the production of certain proteins that are part of viruses. It is given with another antiviral medicine to determine its effectiveness.

The company announced on September 1 that it had started clinical trials targeting approximately 1,140 outpatients at low risk of severe disease to confirm the drug’s efficacy and safety.

• In Japan, the Japanese Pharmaceutical company Shionogi develops new protease inhibitor medication.

The company launched clinical trials with a small group of patients in July 2021 to test the drug’s safety, and aims to enter the final phase of clinical trials targeting more patients before the end of the year. The company also plans to file for approval by 2021.

A company representative noted, “In a very similar way to how we deal with influenza, we can only enter a post-COVID era when the three pillars of prevention, diagnosis and treatment are in place. . We are working to accelerate the development of a safe and highly effective oral medicine.

Support the development of new treatments

At a post-Cabinet meeting press conference on September 3, Health, Labor and Welfare Minister Norihisa Tamura commented on oral drugs being developed by various companies.

“If requests are made, special approval is possible. We want to make the drugs available to the public as soon as possible, ”Tamura said, offering encouraging prospects for the drugs to be brought to market early.

On September 7, the Ministry of Health, Labor and Welfare also announced a plan to provide grants to Shionogi and other companies to support the development of new drugs to treat COVID-19.

According to Tsuneo Morishima, visiting professor at Aichi Medical University and expert in COVID-19 treatment and drugs, “What we need most is an oral drug that can be taken by anyone. anyone anywhere, like the flu medicine, Tamiflu. If a highly effective oral drug capable of quickly curing an infection were developed, it could be used worldwide and become a major weapon against COVID-19 alongside vaccines. ”

(Find access to Sankei Shimbun report in japanese on this link.)

Author: Yukiko A