An experimental new study has recently tested the efficacy of favipiravir (Avigan) for treating COVID-19.

he anti-flu drug favipiravir (Avigan) could combat the new coronavirus, but people should interpret these results with caution.
Recently, there has been much media speculation around the Japanese anti-flu drug favipiravir (brand name Avigan) being effective against SARS-CoV-2. This is the virus that causes COVID-19.

This is because Chinese officials announced in a press conference that the drug could effectively treat this virus.

Since then, the results of one of the two clinical trials that the Chinese officials cited have become available. We take a look at the findings and explain why people must interpret them with caution.

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Qingxian Cai, of the National Clinical Research Center for Infectious Diseases at The Third People’s Hospital of Shenzhen in China, is the first author of the paper, which now appears in the journal Engineering.

Comparing favipiravir with an HIV drug
As Cai and colleagues explain in their paper, the need for effective antiviral agents capable of combating COVID-19 is dire.

In this context, an efficient approach for drug discovery seems to be to test existing antiviral drugs and see whether or not they are suitable for repurposing.

Healthcare professionals have previously used drugs such as ribavirin, interferon, favipiravir, and lopinavir/ritonavir to treat severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome. These are diseases caused by other coronaviruses. However, the efficacy of some of these drugs is questionable, warn the researchers.

That said, past studies that Cai and team cite in their paper have shown that favipiravir, the anti-flu drug, successfully inhibits SARS-Cov-2 in some cultured cells and protects mice against Ebola.

So, the scientists set out to test the results of treating SARS-Cov-2 using favipiravir, and to compare its efficacy with that of lopinavir/ritonavir.

Lopinavir is an HIV inhibitor that emerged as a potential treatment for the SARS outbreak in 2003. Manufacturers often add ritonavir to lopinavir to increase its half life and reduce its side effects.

Favipiravir may combat SARS-CoV-2
The recent study was a non-randomized comparison of two treatment regimens across time. Participants were all patients at The Third People’s Hospital of Shenzhen.

On day one (in early February), one study group — comprising 35 people, all of whom had a confirmed diagnosis of COVID-19 and met the trial criteria, including age and illness severity — took 1,600 milligrams (mg) of favipiravir twice (in two separate doses), plus inhaled interferon.

On day two and beyond, this group reduced their dosage to 600 mg twice daily, and they kept taking inhaled interferon.

The control group comprised 45 patients admitted in the last week of January. They took lopinavir/ritonavir for 14 days at a dosage of 400 mg, then 100 mg, twice daily, plus the inhaled interferon.

Those who took favipiravir cleared the virus in an average of 4 days. Those in the control group cleared it in 11 days.

The favipiravir group also “showed significant improvement in chest imaging compared with the control arm, with an improvement rate of 91.43% versus 62.22%,” report the researchers.

Statistical calculations showed that favipiravir “was independently associated with faster viral clearance. In addition, fewer adverse reactions were found in the [favipiravir group] than in the control group.”

As Cai and colleagues conclude, “In this open-label non-randomized control study, [favipiravir] showed significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance.”

They add:

“[I]f causal, these results should be important information for establishing standard treatment guidelines to combat the SARS-CoV-2 infection.”

Factors that cast doubt on the findings
Although the health characteristics of the people in the two groups were statistically comparable at the start of the study, there were important differences between them that cast some doubt on these results.

For example, more participants in the favipiravir group were younger and leaner and had the treatment sooner after the onset of symptoms. On the other hand, fewer participants in this group had fever, for instance.

Because the study was so small, such minor differences as these can skew the results — despite the scientists accounting for these factors in the analysis. In other words, the slightest error could bias the findings.

This small study provides some potentially exciting results, but the lack of randomization, the differences in severity of the disease, the differences in age of the two groups, and the lack of blinding of outcomes to the researchers all cast doubt on the findings.

Well-conducted randomized controlled trials are necessary before doctors can use this drug for this purpose in clinical practice.