The anti-influenza drug has shown some promise in the fight against COVID-19, but experts warn that it has known side-effects, and that there is insufficient clinical data for its use.
The Japanese government is actively promoting Avigan to combat the novel coronavirus pandemic, even though some of its own advisers are cautioning that more clinical tests are needed to ensure that this anti-influenza drug is completely safe.
In the weeks immediately after the coronavirus was confirmed to be spreading well beyond the borders of China, where it first emerged in mid-December, several governments turned to their medical experts to ask how soon a cure or a vaccine might be developed. And when it became apparent that targeted medicines might take a year or more to develop, experts began re-examining existing medications to determine whether any that were already in stock might be deployed against the disease.
In Japan, one of the first drugs to be considered was Favipiravir, which was originally developed by Toyama Chemical, a part of the Fujifilm Holdings Corp. conglomerate, and was approved in 2014 for sale domestically under the brand name Avigan. Testing in the development stages revealed, however, that the drug can result in elevated blood uric levels and cause deformities in the unborn young of animals.
Based on those results, the company has never conducted clinical tests of Avigan on women who are known or suspected to be pregnant, meaning that the possible effects are not known.
Before the emergence of the coronavirus, research suggested that Avigan had a degree of effectiveness against Ebola in mice, although its impact on the disease in humans has not been proven. Similarly, the medicine has a degree of effect in tests involving animals infected with the West Nile virus, the yellow fever virus, foot-and-mouth disease and the Zika virus, as well as rabies.
Avigan was mentioned in a series of high-level government meetings in March as potential treatment, with media reports suggesting that Prime Minister Shinzo Abe was particularly keen to start using its stockpiles as soon as possible.
That met with a degree of resistance from the Ministry of Health, Labor and Welfare, with bureaucrats pointing out the drug’s history of side effects and the absence of clinical trials that prove conclusively that it is effective against the coronavirus.
“The Japanese government has been strongly recommending Avigan, but we feel that we still need more evidence to show its efficacy,” said Kazuhiro Tateda, president of the Japan Association of Infectious Diseases and a member of the special committee set up by the government to combat the spread of the virus.
“The government says it is a good drug because there have been some reports that suggest it is effective, but we also know there have been adverse reactions in the past with aborted fetuses and damage to unborn children,” he said.
“On the other hand, the group of people most at risk from coronavirus are the elderly, so there is less concern about birth defects with that age group,” he said.
Nevertheless, the government’s medical advisers are still refusing to recommend that Avigan be widely used because there is still a shortage of clinical data.
Competition with China
Tateda believes there may be another motive behind the government’s support for Avigan.
Pointing out that a number of other countries — including local rival China — are also apparently on the cusp of developing and deploying drugs to fight coronavirus, he admitted, “It’s a drug made by a Japanese pharmaceutical company, so there may be political issues behind the decision.”
The Japanese government confirmed that it has received requests “from about 30 countries” for supplies of Avigan and that the medication will be provided to states that want it free of charge.
To meet growing demand, Fujifilm announced on Wednesday that it has expanded manufacturing capacity to “significantly increase” output and that it expects to have produced 100,000 courses of treatment by July. That figure will rise to 300,000 courses by September, it said in a statement, while the company is negotiating partnerships with companies in Japan and abroad to carry out the manufacturing processes and to produce the raw materials required for the drug.
It added that clinical trials are taking place on people who have contracted the coronavirus in Japan, China and the United States.
‘Situation more serious’
“The situation in Japan seems to be getting more serious, so it’s good to see positive developments like Avigan,” said Yoko Tsukamoto, a professor at the Health Sciences University of Hokkaido who specializes in infection control for nurses.
“I saw that clinical trials in China have shown that the drug is effective in about 70 percent of cases,” she said. “It’s logical that a drug that is in stock has been available for some time and is showing good results should be provided to people who need it. It is appropriate for the government to promote Avigan.”
Tsukamoto also played down the possible side effects of the drug, on the grounds that those most in need of the medicine — the elderly — are unlikely to be pregnant.
The Japanese government is awaiting the results of ongoing tests but is expected to officially approve the drug for use against the coronavirus this summer.
By Julian Ryall
Image: (@picture-alliance/dpa/Kimimasa Mayama)