Shionogi's antiviral underperforms in global COVID-19 trial

Shionogi's ensitrelvir, branded as Xocova in Japan, initially received emergency approval from Japan’s Ministry of Health, Labor and Welfare in November 2022, followed by a standard approval in March. Although global interest in COVID-19 treatments has waned, Shionogi has been striving to position ensitrelvir as a competitor on the international stage. However, a recent clinical trial in the U.S. has posed challenges to these ambitions.

The SCORPIO-HR trial, a global phase 3 study, evaluated the effectiveness of ensitrelvir, a once-daily protease inhibitor in the same class as Pfizer’s Paxlovid and Merck’s Lagevrio. The trial focused on whether the drug could significantly reduce the time to sustained resolution of 15 common COVID-19 symptoms. Unfortunately, ensitrelvir did not meet the primary endpoint of the study, failing to show a statistically significant reduction in symptom resolution time.

In the study, sustained resolution was defined as the complete absence of COVID-19 symptoms for at least two consecutive days. Participants received either ensitrelvir or a placebo within three days of symptom onset. Despite the overall failure, a predefined supportive analysis indicated a significant difference in the resolution time of six specific symptoms for those taking ensitrelvir. Additionally, the drug demonstrated a potent antiviral effect by significantly reducing baseline viral RNA levels.

The SCORPIO-HR trial included symptomatic, non-hospitalized COVID-19 patients from North and South America, Europe, Africa, and Asia. Most participants were vaccinated, and about 30% had health conditions such as obesity, diabetes, or hypertension, which increased their risk for severe disease. The trial was conducted during the predominance of the omicron variant of the virus.

Shionogi collaborated with the National Institute of Allergy and Infectious Disease (NIAID) as part of the National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership. The U.S. FDA had previously granted ensitrelvir fast-track designation in 2023.

Dr. Simon Portsmouth, Shionogi’s head of clinical development, acknowledged the mixed results but emphasized the antiviral effect and existing clinical data from Asia. He stated that the company would continue to work with regulatory bodies to explore ways to make ensitrelvir available.

In Japan, the initial emergency approval of Xocova was based on data showing the drug's ability to reduce five common omicron-related symptoms—such as stuffy or runny nose, sore throat, cough, fever, and fatigue—24 hours faster than a placebo. This approval led to a supply agreement with the Japanese government for 1 million courses of the drug, later increased to 2 million courses, resulting in sales of 100 billion Japanese yen ($642 million).

Shionogi’s CEO, Isao Teshirogi, Ph.D., told Reuters in February that Xocova could potentially generate $2 billion in annual sales if approved in the U.S. For 2023, he anticipated sales of around $1 billion to $1.5 billion. The company has yet to release its full-year financial results for the fiscal year ending March 31, 2023.

Despite these efforts, the market for COVID-19 drugs and vaccines has shrunk significantly as the world transitions from pandemic to endemic status, leading to a decrease in demand and even the destruction of excess doses purchased by governments during the pandemic. Over the past weekend, Kyodo News reported that Japan plans to dispose of 77% of the oral COVID antivirals it procured, including Shionogi’s Xocova, Paxlovid, and Lagevrio, due to their impending expiration. This stockpile is valued at approximately 300 billion Japanese yen ($1.93 billion).