China approves first homegrown COVID antiviral

China’s drug regulator granted conditional approval on Monday for an HIV drug to be used to treat COVID-19. The drug, Azvudine, developed by Chinese drugmaker Genuine Biotech, is the first oral antiviral for the disease made in China.

Genuine Biotech, headquartered in Pingdingshan, applied for regulatory approval earlier this month. In an announcement, the company said that 40% of people with COVID-19 who were given Azvudine for a week in a phase III clinical trial showed “improved clinical symptoms”, compared with 11% of those given a placebo. However, detailed data from the trial, including whether the treatment reduced the risk of hospitalization or death, have not been released.

Although drug-efficacy data are lacking, Jun Wang, a pharmacologist at Rutgers University in New Brunswick, New Jersey, says because Azvudine is already approved in China as an HIV treatment, it should have abundant safety data, which would have fast-tracked its application. Genuine Biotech will need to submit more post-marketing data in order for the drug to receive full approval.

Most antivirals target two SARS-CoV-2 proteins that are essential for replication, a polymerase and a protease. Azvudine tricks the virus’s polymerase into incorporating the drug into its RNA, which stops the virus from replicating¹.

In China and globally, the demand for COVID-19 therapies is enormous, says Sheng Ding, a pharmaceutical chemist at Tsinghua University in Beijing. Until the Azvudine authorization, China had approved only one oral antiviral to treat the disease, Paxlovid, developed by Pfizer in New York City. It is highly effective — it reduces the risk of hospitalization and death by nearly 89% — but supplies in China are limited. “The market will have room for several more drugs that may not outperform Paxlovid, but allow more people to access effective therapies,” adds Ding.

Another Chinese-made oral antiviral, VV116, is in the final stages of development, and another dozen are in various stages of development.

Oral remdesivir

The developers of VV116, Shanghai Junshi Biosciences, plan to seek regulatory approval soon. VV116 is essentially a pill version of the intravenous drug remdesivir, made by Gilead Sciences in Foster City, California, and the first drug approved by the US Food and Drug Administration for treating COVID-19. Shanghai Junshi Biosciences slightly tweaked the remdesivir formula and was granted a patent to manufacture it as a pill. It is already being used in Uzbekistan.

A phase III trial of VV116 in China compared its effectiveness and safety with that of Paxlovid. The company says that people with COVID-19 who received VV116 had their symptoms alleviated faster and tested negative sooner than those given Paxlovid, but detailed data from the trial have not yet been released. A small peer-reviewed trial involving 136 participants suggested the drug could reduce the period between the first positive COVID-19 test result and the first negative result to 8.5 days, compared with 11 days for those who received a placebo. But scientists say it is unclear how effective the drug is at reducing the risk of hospitalization and death.

Wang says he expects VV116 to work to some extent, but it’s unclear whether it will outperform Paxlovid. VV116 also blocks viral replication and, like Azvudine and Paxloivd, works best when taken soon after infection.

Scientists say it is difficult to assess the efficacy of Azvudine and VV116 because no detailed data from their phase III trials have been released. “With very limited data, I can’t really tell which one is better,” says Ding, who also leads a team at the non-profit Global Health Drug Discovery Institute, based in Beijing. That team is working on an experimental antiviral for COVID-19, expected to enter clinical trials later this year.

Unlike most countries, China continues to implement its strict ‘zero-COVID’ policy, which involves measures such as mass testing and strict quarantine to quash all infections. The approval of effective COVID-19 antivirals probably will not change that policy, Wang says.

But Hongtao Yu, a biologist at Westlake University in Hangzhou, China, who is also developing an experimental COVID-19 treatment that might soon enter clinical trials, says that could change if the country can build up a “large stockpile of these pills, which are made very affordable, we can make sure the drugs are widely available in hospitals and pharmacies for the vulnerable. That’s when I think China is ready to open up.”