The study did not achieve its primary endpoint of achieving a sustained 2-day resolution of 15 COVID-19 symptoms. Although, ensitrelvir showed a numerical reduction in time to symptom resolution compared to placebo in the primary and several prespecified supportive analyses. It demonstrated antiviral effectiveness and a low occurrence of viral rebound, without any symptomatic rebounds observed in either treatment group. Ensitivevir was well tolerated with no new safety concerns identified.
Of the 2,093 participants, 1,888 (90%) initiated treatment within three days of symptom onset. Among those with positive viral cultures at enrollment, a higher proportion became culture-negative by Day 4 with ensitrelvir compared to placebo.
The study enrolled adults aged 18 years and older with laboratory-confirmed active SARS-CoV-2 infection, with symptom onset within three days (initially within five days) before treatment initiation. Primary endpoints included time to sustained resolution of 15 COVID-19 symptoms over 29 days.
The viral rebound occurred in 0.6% of ensitrelvir-treated and 1.4% of placebo-treated participants by Day 29; no symptomatic viral rebound was observed. COVID-19-related hospitalizations were reported in three (.3%) ensitrelvir-treated and one (.1%) placebo-treated participant; no deaths occurred. Treatment with ensitrelvir was well tolerated, with a similar adverse event profile to placebo.
Secondary endpoints included checking if the virus was no longer detectable by Day 4, tracking any return of the virus or symptoms, evaluating safety, and monitoring changes in the amount of virus RNA in the nose and throat from Day 1 to 4. Statistical methods used a step-by-step approach with a significance level of .05. Other outcomes examined included hospitalizations related to COVID-19, deaths from any cause up to Day 29, and whether COVID-19 symptoms persisted or appeared late.
Key Takeaways
- Ensitrelvir reduced time to symptom resolution compared to placebo, suggesting potential efficacy in managing COVID-19 symptoms.
- The drug demonstrated strong antiviral effectiveness with minimal viral rebound and no symptomatic rebounds observed, indicating effective control of viral replication.
- Ensitrelvir was well tolerated with no new safety concerns identified, achieving standard approval in Japan and undergoing Fast Track review by the FDA, marking significant progress in regulatory approval for broader use.
Background Information
As of March 2024, ensitrelvir has secured standard approval in Japan and is currently undergoing Fast Track review by the FDA following emergency approval. In February 2024, Contagion reported initial results from the ongoing phase 3 study on ensitrelvir, demonstrating its ability to shorten the duration of the five most common COVID-19 symptoms like runny/stuffy nose, sore throat, cough, feverish sensations, and fatigue by approximately one day compared to placebo. These findings are from the phase 3 segment of the SCORPIO-SR trial, double-blind, randomized, and placebo-controlled, involving patients with mild to moderate COVID-19 in Japan, South Korea, and Vietnam.
Building on this, in May 2024, Contagion updated on the SCORPIO-HR trial's outcomes, focusing on ensitrelvir's effectiveness in managing COVID-19 amidst regulatory challenges. While the study did not achieve its primary goal of reducing the time to sustained resolution of 15 common COVID-19 symptoms compared to placebo, a secondary analysis targeting six symptoms showed a significant decrease in resolution time with ensitrelvir. The drug exhibited antiviral effects by reducing viral RNA levels and culture positivity, and no symptomatic viral rebound was observed.3
These findings emphasize the complexities in assessing antiviral efficacy against symptom-based endpoints in evaluating new COVID-19 therapies, highlighting the ongoing need for research and careful interpretation of clinical outcomes. Ensitrelvir has been administered to over one million individuals in Japan, indicating its impact and ongoing evaluation in diverse populations.
References
Chew K, et al. Efficacy and safety of ensitrelvir in non-hospitalized adults at standard or high risk of progression to severe COVID-19: the SCORPIO-HR phase 3, randomized, double-blind, placebo-controlled trial. Presented at International AIDS Conference 2024. July 22-26, 2024. Munich, Germany. Poster 11987.
