New COVID-19 Oral Antiviral Approved For Use In Japan

Health authorities in Japan have issued emergency approval to a new oral antiviral treatment for COVID-19 called ensitrelvir. The once-daily pill works in ways similar to Pfizer’s Paxlovid, and initial Phase 3 results indicate it shortens the duration of symptoms associated with COVID-19.

The new antiviral has been developed in collaboration between researchers at Hokkaido University and Shionogi, a large Japanese pharmaceutical company.

Pfizer’s well-known COVID antiviral Paxlovid is also a protease inhibitor.

Ensitrelvir works a little differently, making it the first “Nonpeptidic” and “Noncovalent” oral protease inhibitor to reach clinical use. As a result, ensitrelvir can be taken once a day and without ritonavir, the second drug added to the Paxlovid formulation to slow metabolism of the protease inhibitor.

Shionogi initially applied to Japan’s regulatory bodies back in February, after the first data from its Phase 2/3 trial in Asia began trickling in.

At the time health authorities in the country hit pause on the authorization, calling for more trial data.

By late September Shionogi announced it had reached its primary Phase 3 endpoint, demonstrating the antiviral successfully shortens a patient’s symptomatic period by 24 hours compared to placebo.

The trial also demonstrated the antiviral significantly reduced viral RNA levels by day four of treatment, compared to placebo.

Unlike other antiviral Phase 3 trials conducted at earlier stages in the pandemic, ensitrelvir has been tested in a primarily vaccinated population during a period of Omicron-dominated transmission.

While the preliminary results from this Asian Phase 3 trial have been enough for Japanese health authorities to give the antiviral an emergency approval, other international regulatory bodies may be waiting for data to come from a large global Phase 3 trial that kicked off earlier this year.

Around 1,500 participants will be recruited to take either a five-day course of ensitrelvir or placebo. As with Paxlovid, the treatment must be started within the first five days of symptoms appearing. Much like the prior Phase 3 trial, the primary endpoint will involve tracking the time to symptom resolution.

Annie Luetkemeyer, lead investigator on the Activ-2d trial, said the value of ensitrelvir over Paxlovid is that it is only a single pill, taken once a day.

“S-217622 has the potential to simplify COVID-19 treatment, as it is administered once a day without a boosting agent,” Luetkemeyer said in August when the trial was first announced.

The arrival of ensitrelvir marks the third SARS-CoV-2 antiviral to reach clinical use after Pfizer’s Paxlovid and Merck’s molnupiravir.