A Drug Developed to Fight Ebola Could Hold Hope for Coronavirus Treatment

Last year, when I visited the town of Beni, in the Democratic Republic of the Congo (DRC), people did not shake hands. Bottles of disinfectant and buckets of chlorinated water were at the entrance of every business. Misinformation spread across social networks and on news-sites, and treatment centers in the northeastern province of North Kivu were being attacked by armed militias.

At the time, Beni was one of the centers of a devastating Ebola outbreak, the second most deadly in world history. According to the World Health Organization, almost 3,500 people were sickened by the virus, and more than 2,000 died, a case fatality rate of 66%. “It’s a really difficult situation,” Sister Xeverine, a Catholic nun who ran a UNICEF-supported creche for children whose parents had been diagnosed with the disease, told me when I saw her in Beni. “Medical workers need to convince the community that they need to be treated.” She continued, “on the other side, there are people who always influence people to refuse treatment.”

The Ebola outbreak in North Kivu seems to have come to an end just as the coronavirus panic struck Europe and the U.S.—the WHO says there has not been a new case of Ebola since Feb. 17 this year. Despite the marked differences in how the viruses operate (Ebola is far more deadly than coronavirus, and it is only transmitted through infected bodily fluids, while COVID-19 is believed to be transmitted through airborne droplets), there are many similarities in the range of public response, from denial that the disease is a problem to contact tracing and mandatory quarantining for people who have potentially contracted the illness.

In January this year, Dr. Richard H. Kaszynski, the co-founder of Stanford Solutions, a healthcare innovation group out of Stanford Medical school, and Koichi Yamada, a scientist at Japan’s Toyama Chemical Company, travelled to North Kivu to discuss the use of favipiravir, a post-exposure treatment for Ebola. Animal trials had shown an increase in survival rates when the drug was administered and human testing during the 2015 West African outbreak of the disease suggested that the drug could be potentially life-saving to patients who had low to moderate levels of the virus in their blood—like medical staff who accidentally exposed themselves to Ebola, and others who had recently contracted the illness.

On the penultimate day of his trip to North Kivu, Kaszynski, who is a senior medical advisor to the Congolese government, began hearing about a virus spreading from Wuhan, China. He and Yamada wondered whether favipiravir, the drug he was suggesting could be helpful against Ebola, might be of use against the novel coronavirus.

Favipiravir was originally developed to treat influenza by Toyama Chemical, which is owned by Fujifilm, the Japanese photography company that now has sizable holdings in biomedicine. The drug was marketed under the name Avigan, and in 2014, was approved in Japan for human use. “The Japanese government stockpiled 2 million courses for use against influenza,” says Yamada, who is the president of Toyama’s director of international affairs and is heading the company’s favipiravir effort.

Along with Japan, several countries have built up reserves of the drug over the years. The U.S. Department of Defense bought 6,000 courses of the drug in 2016 as a potential therapeutic against the seasonal flu and the government of the United Arab Emirates stockpiled 50,000 courses as a potential therapeutic against MERS (Middle East Respiratory Syndrome, caused by a coronavirus in the same family as the virus that causes COVID-19.) China has an unknown quantity of the drug, but its stockpile is likely significant, since Chinese factories have recently been producing generics (the patent for Avigan has expired in China and Zhejiang Hisun Pharmaceutical, a Chinese company, has begun to produce it). According to POLITICO, the Trump administration is reportedly pressuring the U.S. Food and Drug Administration to allow favipiravir as a potential treatment for the novel coronavirus. The FDA, however, has not yet approved the drug for human use.

Kaszynski and Yamada swiftly realized that, like influenza A and B, which are two primary causes of the seasonal flu, SARS-CoV-2, which causes COVID-19, is an RNA virus—which means Fujifilm’s drug could, potentially, work against it. “Specifically, favipiravir targets something called an RNA polymerase, basically an enzyme that the virus needs to replicate itself inside of a cell,” Kaszynski says. “The coronavirus has the same enzyme that the influenza virus has.” A 2018 paper by Belgian scientists suggested that favipiravir might be developed as a broad spectrum anti-viral against “neglected and emerging RNA viruses.”

On Feb. 4, only a few days after Kasynski and Yamada returned from DRC, the journal Cell Research published a letter to the editor from Chinese researchers that recommended live trials of several drugs, including favipiravir, to judge their effectiveness against the new coronavirus. At the time “I was thinking most probably it’s going to work,” says Kaszynski.

Even as Japan has allowed off-label use for the drug against COVID-19, Fujifilm have been careful not to trumpet the effects of their drug. “The scientific evidence is limited,” Yamada says, and it is unclear on what level of severity cases the drug will work. As with Ebola, the drug appears to work better on people who have lower levels of the novel coronavirus in their system, but dosing at the moment is still being worked out. Guidance by the Japanese Association for Infectious Diseases, a medical society based in Tokyo, from late February noted, “it is unknown as to the appropriate severity and timing for administration.”

As COVID-19 spread around the world in February, trials began in China on the new drug, and on March 18, an official at the Chinese health and technology ministry announced that the drug had been “clearly effective” in treating 340 patients. One of the trials, at the Third People’s Hospital of Shenzhen showed the drug “was independently associated with faster viral clearance,” and that 35 patients who received the drug cleared the virus in four days, whereas a control group of 45 patients in the same facility who did not receive the drug took 11 days to clear the virus. A separate multi-center comparative clinical trial in China indicated that favipiravir reduced fever and coughing in COVID-19 patients quicker than another drug, Arbidol, and had a seven day recovery rate.

Kaszynski and Yamada both say that the results out of China were not definitive, and that we need more clinical trials of favipiravir. The scattered nature and “individual basis” of the off-label use in Japan makes it “nearly impossible to judge whether favipiravir is effective or not,” Yamada says. “That’s why we need to have a clinical study.” Toyama recently announced that the group would begin a clinical trial on 100 patients afflicted with the novel coronavirus for 14 days.

At around $5 a pill, and $650 for a full course, favipiravir is relatively cheap, and easy to mass produce. One of the lessons learned from treating health crises in poor countries like the Democratic Republic of the Congo, Kaszynski notes, is to ensure that treatments are easily producible, and will not cripple economies for years after an epidemic has been resolved. Because of the scale of the COVID-19 pandemic and the economic damage it has wrought, the price point of any therapeutic is an important factor.

Since favipiravir comes in pill form, it could be given to people with mild symptoms who might put a strain on already-stretched hospital resources, and courses would be able to be distributed to people quarantining at home, rather than requiring hospital staff to administer them through injections, or otherwise. Unlike other drugs, Kaszynski points out, favipiravir wouldn’t need to be kept temperature-controlled, making it easier to transport and distribute to people who are suffering from the virus.

But there are reasons to be cautious. Many of the drugs currently being touted as possible solutions to COVID-19 come with many strikes against them. For example, U.S. President Donald Trump tweeted recently that chloroquine, a common anti-malarial, could be a treatment against the new coronavirus, even though his own infectious disease specialist said that its effects remained unproven. Shortly after Trump’s advertising of the drug, two people in Lagos, Nigeria, were rushed to hospital after overdosing on the medicine.

It has also been suggested that remdesivir, an injectable drug created by Gilead Science, an U.S. pharmaceutical company, could be of use against the virus, although concerns have surfaced about how it affects liver enzymes. And a study published March 18 by the New England Journal of Medicine indicated that in 99 patients treated with the combination antiviral Kaletra, an early frontrunner in the race for a cure, “no benefit was observed” from the medicine. (Still, some continue to believe Kaletra is effective: the government of Israel, for example , has approved a generic version of the drug to be used against COVID-19.)

Favipiravir itself has its skeptics. After Japan’s Prime Minister Shinzo Abe was optimistic about the drug in a Feb. 29 press conference, the Wall Street Journal noted that the drug had been shown to disturb the development of animal embryos. For his part, Yamada says that based on the drug’s testing for influenza, “there is a very good safety database” on the drug and that no adverse effects, including on unborn embryos, had been registered from the drug.

Kaszynski says that the early bad press has harmed favipiravir’s image. “Everybody has kind of, you know, treated this as the boogey man of the lot, and that’s not the case,” he says. The drug has been well tolerated by patients so far, and there have been no serious adverse effects on human trial subjects. As a result, in the early stages of the COVID-19 outbreak, he says, “basically no-one was looking at it.”

That might be because the discourse around managing COVID-19 has centered around creating a vaccine to combat the virus.“ In some areas, particularly the United States, there’s a lot of talk about a cure. In Europe, it’s not spoken about so much,” says Guy de Selliers, a corporate advisory expert who is working with InfraSalience, a recycling company whose work focuses on reducing air pollution, to connect doctors and scientists who wish to do trials of favipiravir to governments. “People talk about a vaccine and they talk about 12 to 18 months,” he says, whereas a therapeutic could potentially be prepared in a few weeks. If the drug is easy to create and distribute, it might help to mitigate the suffering imposed upon populations by extended periods of quarantine.

Kaszynski says he would scrap trials if favipiravir proved to be harmful—but stresses that its benefits for people with COVID-19 needs to be better understood. Along with China and Japan, doctors and scientists in Turkey, Israel, Russia and other countries have already begun using and testing the drug. “It’s one of the few options that humanity has that we haven’t really explored to its fullest potential,” he said. Not to do so, he continued, “would be just a tremendous disservice to humanity.”

Niarchos is a writer based in New York. His work has appeared in The New Yorker and other magazines and newspapers. He is currently working on a book about the global cobalt trade.

 

 

 

 

 

from Health – TIME https://ift.tt/2xEd9cA