Insufficient proof behind rejection of Shionogi COVID-19 drug

By Kiyohiko Yoneyama and Chisato Yomon / Yomiuri Shimbun Staff Writers

16:53 JST, July 21, 2022

A COVID-19 pill developed by Shionogi & Co. has failed to win fast-track emergency approval because experts sought scientifically convincing data to prove its efficacy, rather than focusing on the need for more treatment options amid the seventh wave of novel coronavirus infections.

The decision not to approve Xocova as the first domestically produced pill for COVID-19 patients with mild to moderate symptoms was made at a joint meeting Wednesday of subgroups of the Health, Labor and Welfare Ministry’s Pharmaceutical Affairs and Food Sanitation Council.

Discussions at the meeting were heated, with one member calling for Xocova to be approved as a “positive factor amid the heightened sense of crisis due to the fresh surge in new cases.” Another member disagreed, saying: “It’s unacceptable for the evaluation criteria of clinical tests to be changed retroactively. The drug’s efficacy cannot be confirmed.”

Experts at Wednesday’s meeting were divided because interim data submitted by Shionogi showed one of the two goals set for Xocova’s clinical trials had yet to be met. The pill was confirmed to be effective in reducing the amount of coronavirus in the body, but it was not sufficiently clear that it improved the overall 12 symptoms associated with COVID-19.

Shionogi said enough data could not be collected regarding certain symptoms typical for the delta variant such as nausea and diarrhea, because the clinical trials were conducted amid the prevalence of the omicron variant, during which there were fewer cases with these symptoms.

When it comes to respiratory difficulties and fever, some of the typical symptoms for the omicron variant, Xocova was seen as effective in improving them, Shionogi added.

A review report from a government-sponsored independent organization was submitted at the joint meeting. “It cannot be denied that the pill can help reduce the amount of coronavirus in the body,” the report said. “However, it cannot be concluded that its efficacy can be presumed.”

Based on this report, more experts at the meeting said it was difficult to conclude that Xocova was effective in improving COVID-19 symptoms. It was eventually decided not to grant emergency approval to the pill.

Blow to exit strategy

So far, two types of pills have been put into practical use in Japan, but they can be administered only to patients at high risk of serious illness. The two drugs have not been widely used as initially expected because of the inconveniences involved, such as the size of their capsules and the number of medications that cannot be taken together.

Many medical professionals are therefore hoping that a pill that is easy for them to prescribe will be made available, because such a drug could prompt more clinics to handle COVID-19 patients and help the disease to be eventually treated like a common illness, such as seasonal flu.

Also, the two drugs are produced overseas, so it might be hard for them to be procured should the international situation become unstable. Therefore, there have been high hopes for approving a domestically produced COVID-19 drug from the standpoint of enduring stable supply.

Shionogi conducted the clinical trials with a wide range of people with the aim of allowing Xocova to be prescribed to patients regardless of their risk of serious illness. Through the clinical trials, however, it was found that the pill cannot be administered to pregnant women or taken together with several drugs.

Wednesday’s decision made it clear that the nation has taken a step back in realizing its exit strategy from the pandemic.

Shionogi is conducting the final stage of clinical trials using Xocova, with data expected to be compiled this autumn. The pill still might get an official nod if its efficacy can be confirmed by the data.