While researchers globally scramble to develop a new antiviral to treat the novel coronavirus, doctors in Japan are working around the clock to verify the effectiveness of drugs repurposed to treat patients with serious respiratory problems.

As the pandemic threatens to overwhelm hospitals around the world, doctors have been forced to turn to drugs developed to cure other illnesses because it will be a drawn-out process to work on an antiviral to treat COVID-19, the pneumonia-like disease caused by the coronavirus, from scratch.

Candidate drugs include those developed to treat influenza, HIV, hepatitis, acute pancreatitis and asthma.

“We can save time in the development of new antivirals as we already know how existing medications work in the body and their side effects,” said Atsuo Hamada, a professor of travel medicine at Tokyo Medical University.

But doctors still face a hurdle as they are required to gain consent from COVID-19 patients before administering repurposed drugs not approved for this health issue by the health ministry.

Among the drugs drawing most attention in Japan are Avigan, an anti-flu medicine manufactured by Fujifilm Toyama Chemical Co., and Orbesco, a drug to treat asthma produced by Teijin Pharm Ltd. 

Prime Minister Shinzo Abe signaled at a March 28 news conference that Japan would embrace the use of Avigan.

“(Avigan) has been used in dozens of cases and there have been reports that the drug has been effective in improving symptoms,” he said. “We are set to expand clinical trials of the drug by collaborating with countries seeking to use it.”

Fujita Health University is among research institutions that have embarked on clinical tests of Avigan for coronavirus patients.

At the University of Tokyo’s Institute of Medical Science, doctors are engaged in a study on the combined usage of Avigan and Fusan, a drug to treat acute pancreatitis.

As for Orbesco, the Kanagawa Prefectural Ashigarakami Hospital announced March 2 that it had administered the medication for three patients.

It said the symptoms of all three individuals improved about two days after inhaling the asthma drug. Two of them have recovered sufficiently that they no longer need to be on ventilators.

The National Institute of Infectious Diseases and other research institutes found that Orbesco is effective in curing Middle East Respiratory Syndrome, an illness caused by another strain of the coronavirus.

Their studies showed that Orbesco is also effective in curbing the growth of the new coronoavirus.

The Japanese Association of Infectious Diseases was hugely encouraged by the finding, calling it "significant" in light of the fact that no silver bullet has yet emerged to treat the coronavirus. The association decided to continue with clinical trials of Obresco.

“Although cases are still limited, we can safely assume that those drugs are effective to a certain degree,” said Tsuneo Morishima, a visiting professor of infectious diseases at Aichi Medical University.

But some experts are urging caution, citing potential side effects when using repurposed drugs. Others remain skeptical about their efficacy in treating the coronavirus.

Avigan is not usually administered to treat flu patients. It is stockpiled by the Japanese government in case other anti-flu drugs fail to prove effective in curing new strains of influenza.

Avigan cannot be prescribed to pregnant women and those who plan to fall pregnant because tests on animals showed it can result in defective offspring.

Orbesco, on the other hand, can temporarily weaken a person's immune system when treating asthma symptoms, which could lead to a rapid growth of the virus.

Doctors at the Sapporo City General Hospital reported that the condition of patients did not improve when Orbesco was prescribed. Some patients died and others became so ill they required extracorporeal membrane oxygenation (ECMO) treatment.

Researchers assessed the efficacy of Avigan and Orbesco on coronavirus patients by analyzing cases in which the medications were used.

The standard way of scientifically evaluating the effectiveness of a medicine is through a randomized controlled trial, in which subjects are assigned the drug by chance.

So far, the benefits of these drugs in curing COVID-19 have not been confirmed in randomized controlled trials.

“Individual reports saying ‘we used this drug and it worked’ are inconclusive in terms of determining its effectiveness and harm,” said Rokuro Hama, an internist and head of the nonprofit Japan Institute of Pharmaco-Vigilance. “If this situation persists, it will not be possible for any patient to benefit.”

Some researchers have conducted randomized controlled trials on some candidate drugs.

A Chinese team reported that Kaletra, a drug used to treat HIV that was regarded as promising in the treatment of COVID-19, did not prove effective in a trial involving 199 subjects.

An international team of scientists, including researchers from the United States and South Korea, are set to hold a clinical trial by repurposing Remdesivir, a medication to treat Ebola virus infection.

Researchers have high hopes that Remdesivir’s efficacy in inhibiting the multiplication of the virus may work for the coronavirus, too.

They said that 400 or so patients who developed pneumonia after contracting the coronavirus will be examined to help gauge whether the drug is beneficial in a randomized controlled trial.

Japan’s National Center for Global Health and Medicine is expected to join the international endeavor.

“An important first step is to pick a standard drug” for the treatment of COVID-19,” said Norio Omagari, director of the center’s Disease Control and Prevention Center. “If it is set, we can compare other potentially promising medications with the drug to ascertain their effectiveness.”

(This article was written by Ryosuke Nonaka and Hajime Mikami.)