Clinical Trials for Oral Drugs Against COVID-19 in Full Swing

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

In particular, an oral drug that can be taken like cold medicine in the early stages of infection could not only prevent those who become infected from developing severe symptoms, but also reduce the burden on healthcare facilities. 

Clinical trials of several new drugs are underway both in Japan and around the world, and some have reached the final stages before commercialization.

Preventing Severe Cases, Spread of Infection

Drugs currently approved in Japan for treating COVID-19 include the following medications:

• Remdesivir, an antiviral medication; 
• 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.
• Sotrovimab, a single dose monoclonal antibody for the treatment of COVID-19

Two of the above treatments were just approved for use this year.

The “antibody cocktail” received special approval for use in Japan in July 2021, and is indicated for patients with mild cases. The range of patients eligible to receive the drug was expanded to include outpatients in August this year in order to help cope with the rising number of persons recuperating at home. 

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

In addition, Sotrovimab was just approved for use in Japan on September 27, 2021, by the Ministry of Health, Labor and Welfare. The infusion style treatment was developed by GlaxoSmithKline K.K. (GSK) and Vir Biotechnology, and has already been approved for use in the United States.

Sotrovimab is indicated for use by patients with a high risk of aggravation, such as underlying disease and obesity, among mild and moderate cases of COVID-19. It works by preventing the virus from binding to human cells and infecting them. Administered as a single infusion, it, too, is currently not available for use at home.

Oral Medications

The biggest advantage of the oral antiviral drugs currently being developed 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 recovering at home could take such a drug immediately after infections were detected, it could not only prevent the development of severe illness, but also stop the spread of infection. 

In addition, these drugs have the potential to provide some relief to overwhelmed healthcare facilities facing hospital bed shortages.

Moreover, as the surface proteins of the virus, which are targeted by the antibodies produced by vaccines, are prone to mutation, some have pointed to the potential for vaccines to lose effectiveness. However, the oral drugs under development act on a different 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

Leading among the different types of oral medications that many companies are currently developing are the following:

• Molnupiravir, being developed by the U.S.-based pharmaceutical giant Merck; 
• AT-527, developed by Swiss pharmaceutical giant Roche. 

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

An international joint clinical trial involving a large group of patients, including patients in Japan, has entered its final stages.

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

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

According to Chugai Pharmaceutical, a subsidiary of Roche, AT-527 was originally developed to treat hepatitis C infections. Now, though, it is being tested on 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.

The final results of clinical trials are expected within the year, and Chugai is aiming to file for approval in Japan in 2022. At a press conference on August 26, project leader at Chugai, Masaya Seki, stated: “The fact that this oral medication prevents mild infections from becoming severe is an extremely important point. We will do our best to increase the production volume.”

• U.S.-based pharmaceutical giant Pfizer is also developing an oral medication, PF-07321332. 

The drug is a type called a protease inhibitor, which prevents the production of certain proteins that form part of viruses. It is being administered alongside another antiviral drug to determine its efficacy.

The company announced on September 1 that it had begun clinical trials targeting roughly 1,140 non-hospitalized patients at low risk of serious illness to confirm the efficacy and safety of the drug. 

• In Japan, the Japanese pharmaceutical firm Shionogi is developing a new protease inhibitor drug. 

The company initiated clinical trials with a small group of patients in July 2021 to test the safety of the drug, and is aiming to enter the final stage of clinical trials targeting a larger number of patients before the end of the year. The company is also considering filing for approval within 2021.

A representative of the company noted: “Very similar 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 hasten the development of a safe and highly effective oral medication.”

Supporting Development of New Treatments

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

“If applications are made, special approval is possible. We want to make the medications available to the public as soon as possible,” Tamura said, offering an encouraging outlook for early commercialization of the drugs. 

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

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

(Find access to the Sankei Shimbun reports in Japanese at this link. )

Author: Yukiko Une