Novel Oral Antiviral Targeting COVID-19 Approaches Authorization

Shionogi & Co., Ltd. today announced that two late-breaking poster presentations featuring results from clinical trials on its novel COVID-19 oral antiviral ensitrelvir would be published as posters at the 33rd European Congress of Clinical Microbiology & Infectious Diseases.

Ensitrelvir, known as Xocova® 125 mg tablet in Japan, received emergency regulatory approval from the Ministry of Health, Labour and Welfare (MHLW) to treat SARS-CoV-2 infection.

Recently, ensitrelvir was granted Fast Track designation by the U.S. Food and Drug Administration (FDA).

The first late-breaking poster presentation included a post-hoc analysis of the Phase 3 part showing that viral rebound and symptom recurrence were infrequently seen up to 21 days after treatment with ensitrelvir.

Viral RNA rebound by PCR testing was observed in 7.8% of the ensitrelvir 125 mg group (n=590) and 4.7% in the placebo group (n=574). Symptom recurrence was rare and was not associated with viral RNA rebound.

Although RNA rebound was observed in a few patients, there was only one (1/310) low-level viral titer positive in follow-up, suggesting no concerns for infectivity or transmission.

A second late-breaking poster presentation included new results from the study (Phase 2b/3 part) of patients who tested positive for SARS-CoV-2 but were either asymptomatic or had only mild symptoms at the time of randomization.

These results were based on 572 patients who were followed up for ten days after randomization. Ensitrelvir 125 mg showed a significant reduction from baseline viral RNA on Day 4, a reduction of 1.12 log10 copies/mL versus placebo (p<0.0001).

The time to the first negative SARS-CoV-2 culture was significantly shorter with ensitrelvir 125 mg compared to placebo (a median time of 38.3 hours versus 66.7 hours, p<0.0001, respectively).

Although these results were exploratory, the reduction in viral RNA and faster time to a negative viral culture may be predicted to reduce the period of infectivity, which may have implications for reducing the risk of transmission.

In a subset of 70 asymptomatic patients, ensitrelvir 125 mg (n=23) showed a numerical reduction in the proportion of patients developing symptoms.

In the 502 patients presenting with mild symptoms treated with ensitrelvir 125 mg (n=171), a numerical reduction in the proportion reporting a worsening of symptoms compared with placebo was observed.

Ensitrelvir was well tolerated, and no new safety concerns were identified.

A separate Phase 3 study of ensitrelvir (SCORPIO-HR) is underway across Asia, Africa, North America, and Europe in non-hospitalized adults who have tested positive for SARS-CoV-2. It includes those with and without risk factors for severe disease and regardless of vaccination status. Shionogi also plans to initiate a post-exposure prevention global Phase 3 study, SCORPIO-PEP.

“We are encouraged by these new data regarding the potential reduction of transmission among asymptomatic patients and patients with mild COVID-19 symptoms,” said Isao Teshirogi, Ph.D., in a press release on April 5, 2023.

“We are continuing to evaluate ensitrelvir in multiple patient populations through our robust global clinical program and look forward to continued scientific exchange on this important compound.”

Ensitrelvir remains an investigational drug outside of Japan and has not been approved outside of Japan. 

Other COVID-19 antiviral news is posted at Coronavirus Today.