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Japanese conglomerate Fujifilm, most famous for its film and instant cameras, does more than sell point-and-shoots: it also makes medical equipment, anti-aging skincare, hair products—and now a potential coronavirus treatment.
In late February, when the coronavirus had sickened 80,000 people worldwide—on Friday the total topped 530,000—and the World Health Organization had not yet declared a pandemic, shares in Fujifilm Holdings Corp soared after Japan’s health minister said the government was considering using a drug called Avigan, also known as favipiravir, to treat patients sickened by COVID-19.
More than a month later, favipiravir has showed promise in two trials involving coronavirus patients, with more countries, all desperate for an answer to COVID-19, prepare to test its effectiveness.
An obscure drug—until now
Favipiravir initially was developed by Fujifilm Toyama Chemical as an anti-influenza drug. Japan approved it for clinical use in treating influenza in 2014. Japan’s Ministry of Health, Labour, and Welfare—which did not respond to an emailed request for comment—maintains a stockpile of favipiravir.
Yet the drug remained relatively obscure—it’s not available on the market in Japan—until the coronavirus outbreak. Now, clinical trials in several countries are studying favipiravir’s effectiveness in combatting COVID-19, with some already reporting good results.
Trials done with 340 patients in the Chinese cities of Wuhan and Shenzhen found that favipiravir was “clearly effective in treatment” of COVID-19 Zhang Xinmin, the director of the China National Center for Biotechnology Development said on March 17.
Zhang said patients who received favipiravir tested negative for the virus in a shorter period of time than patients in the control group, and said favipiravir has been recommended to medical teams treating COVID-19.
Three days later, Indonesian President Joko “Jokowi” Widodo said his country was importing millions of doses of Avigan to treat COVID-19 patients.
Authorities in Italy, which has been badly hit by the coronavirus pandemic, approved new clinical trials to study favipiravir as a COVID-19 treatment on March 22. And a hospital in Thailand is launching a study of several drugs, including favipiravir, to test their efficacy in treating COVID-19.
Combination treatments
Researchers in China, meanwhile, are currently recruiting for clinical trials where COVID-19 patients will take either favipiravir, a drug called tocilizumab—normally used to treat rheumatoid arthritis—or a combination of the two. That study launched on March 8.
Combination treatments with more than one antiviral can be more effective, in part because they lower the chances of drug-resistant virus strains, said Riaz Abbas, a virologist and senior manager of global medical learning and performance at biotech pharmaceutical company Amgen.
“[The favipiravir and tocilizumab trials] would help give us some good and more robust scientific data to say okay, so is favipiravir a better option for patients with COVID-19? Does it work, yes or no? And if it works, does it work better on its own or in combination?” Abbas said.
On March 23, the U.S. Food and Drug Administration approved tocilizumab for a clinical trial to treat hospitalized patients with severe COVID-19 pneumonia. Favipiravir has not been trialled in the U.S. as a potential coronavirus treatment, but the FDA did complete a clinical trial on it in 2015 as an anti-flu drug.
The government go-ahead
Government approval is required for full-scale use of favipiravir to treat COVID-19 in any country. Japan has not officially approved the drug to treat COVID-19, but clinical research on its efficacy started there in March in addition to the ongoing and upcoming trials in Italy, Thailand, and China.
The early trials in Wuhan and Shenzhen are promising, but more robust trials are needed—for example, comparing favipiravir to other drugs, randomizing the selection of patients, and using a larger patient pool—before favipiravir’s efficacy can be properly determined, Abbas said.
“We have no public clinical scientific evidence yet proving the efficacy and safety of Avigan against COVID-19 in patients, so we cannot talk about Avigan at this moment,” a Fujifilm spokesperson said.
Antiviral contenders
For now, favipiravir is a relative underdog among the antivirals that could treat COVID-19.
The frontrunner is Gilead’s remdesivir, which is thought to have the most potential. “There is only one drug right now that we think may have real efficacy and that’s remdesivir,” WHO assistant director-general Bruce Aylward said in late February.
Remdesivir is one of four treatments in the WHO’s “solidarity trial” of antiviral drugs, launched on March 18 to coordinate global studies on potential treatments for the disease. The other three are chloroquine; a combination of lopinavir and ritonavir; and a combination of lopinavir, ritonavir, and interferon beta. Patients in the study will receive one of the four options.
The drugs included in the study, though, are subject to change. If one of the four options has no clear effect, it can be removed from the study, and different drugs can be added.
“My money is on remdesivir. It is quite a promising drug,” Abbas said. But early clinical trial results on favipiravir are encouraging, he said. In fact, favipiravir and remdesivir share an important trait. The coronavirus uses an enzyme called RNA polymerase to replicate itself. Some antiviral drugs work by inhibiting this replication so that the virus cannot multiply. Remdesivir is one such drug; so is favipiravir.
As polymerase inhibitors, remdesivir and favipiravir are the same class of drug, Abbas said. “[But] no two drugs are the same, so we have to test them.”
One challenge, he adds, is that if the WHO study and other ongoing trials show that remdesivir works, there will be “huge” pressure to access remdesivir. The Gilead drug is administered through intravenous infusion, which Abbas said is harder and costlier to produce than tablets, and also needs to be administered in a hospital.
“Some of the significant advantage of favipiravir is that it’s a tablet, so it’s easier to make and cheaper to make,” and thus easier to scale, Abbas said. “We’re in desperate need of medication, that’s pretty clear.”
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