FDA Approves Shionogi's XOCOVA as First Oral Drug for COVID-19 Prevention After Exposure

The U.S. Food and Drug Administration (FDA) has approved XOCOVA (ensitrelvir), an oral antiviral from Shionogi, for post-exposure prophylaxis (PEP) of COVID-19 in adults and adolescents 12 years of age and older. This marks the first and only oral option to help prevent symptomatic COVID-19 following contact with an infected individual.

The approval is based on results from the Phase 3 study SCORPIO-PEP, the only such trial of an oral antiviral to meet its primary endpoint. XOCOVA significantly reduced the risk of developing symptomatic COVID-19 by 67% in uninfected individuals through Day 10 after exposure, compared with placebo. The study enrolled 2,387 participants, with 1,030 receiving ensitrelvir and 1,011 receiving placebo.

XOCOVA was generally well tolerated. Adverse events occurred in 15.1% of the XOCOVA group and 15.5% of the placebo group. The most common adverse events occurring in at least 1% of the XOCOVA group and at a higher frequency than placebo were headache, diarrhea, and cough. There were no reports of altered taste (dysgeusia) attributed to XOCOVA in the trial. The results from the SCORPIO-PEP trial were published in the New England Journal of Medicine on May 14, 2026.

XOCOVA is a five-day oral regimen. The dosing schedule is three tablets taken on the first day and one tablet taken on days two through five. The FDA's approval came ahead of the Prescription Drug User Fee Act (PDUFA) action date of June 16, 2026.

Shionogi previously announced in September 2025 that the FDA had accepted its New Drug Application for review. Ensitrelvir, a SARS-CoV-2 main protease inhibitor, suppresses viral replication by selectively inhibiting a key enzyme the virus needs to multiply. The drug was created through joint research between Hokkaido University and Shionogi.

In Japan, ensitrelvir (known as Xocova) received emergency regulatory approval in November 2022 and full approval in March 2024 for the treatment of COVID-19. Those approvals were based on the SCORPIO-SR study. In 2025, Shionogi submitted two new drug applications in Japan for post-exposure prophylaxis and for treatment in pediatric patients aged 6 to under 12 years.

Ensitrelvir is currently under regulatory review in Taiwan for the treatment of COVID-19 and with the European Medicines Agency for both post-exposure prophylaxis and treatment. It is available in Singapore for treatment via a Special Access Route application. The drug remains investigational outside of Japan and Singapore.

The approval introduces a new prevention strategy in the current therapeutic landscape. COVID-19 remains highly transmissible, driven by Omicron and its subvariants. The U.S. Centers for Disease Control and Prevention estimates that between October 1, 2025, and May 23, 2026, there were 3.8 to 12.4 million new cases in the U.S., resulting in 800,000 to 2.3 million outpatient visits, 120,000 to 240,000 hospitalizations, and 13,000 to 42,000 deaths.

The impact of the FDA approval on Shionogi's consolidated financial results for the fiscal year ending March 2027 has already been reflected in the company's earnings forecast announced on May 12, 2026.