Patients with mild-to-moderate COVID-19 treated with the oral antiviral ensitrelvir (Shionogi and Co.) within 5 days of symptom onset saw their symptoms resolve a day earlier than those who received placebo, according to data from a phase 2/3 randomized clinical trial.
Findings from the SCORPIO-SR trial presented at the 30th Conference on Retroviruses and Opportunistic Infections (CROI) showed that the median time to resolution of 5 common symptoms of COVID-19 was 24.3 hours earlier for patients treated with ensitrelvir 125 mg compared with those receiving placebo (P=.0407).
Ensitrelvir, known as Xocova® 125 mg tablet in Japan, is a novel 3CL protease inhibitor that targets the SARS-CoV-2 virus and recently received emergency regulatory approval as an oral treatment for COVID-19. Ensitrelvir remains an investigational drug outside of Japan, according to a Shionogi press release.
Patients aged 12-69 years with mild-to-moderate COVID-19 infection within 120 hours of symptom onset, regardless of SARS-CoV-2 vaccination status and presence of risk factors for severe disease, were randomized to oral administration of ensitrelvir 125 mg (375 mg loading dose on day 1), ensitrelvir 250 mg (750 mg loading dose on day 1), and placebo once daily, for 5 days. Participants were enrolled across Japan, South Korea, and Vietnam, and over 90% of participants were vaccinated against COVID-19.
The primary endpoint was time to resolution of 5 symptoms of COVID-19: stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness. Secondary endpoints included change from baseline on day 4 in the amount of SARS-CoV-2 viral RNA and time to first negative of viral titer.
Investigators found that the median time to resolution of 5 symptoms was significantly shorter in patients who received 125 mg of ensitrelvir (n=336, 167.9 hours) than those in the placebo group (n=321, 192.2 hours) (P=.0407).
The mean change of viral RNA levels from baseline on day 4 was significantly greater in the 125 mg group (least squares mean change from baseline-2.48 log10 copies/mL) than in the placebo arm (-1.01 log10 copies/mL) (P<.001). The time to first negative of viral titer was significantly shorter in patients in the 125 mg group (n=199, 36.2 hours) than those in the placebo arm (n=211, 65.3 hours) (P<.0001).
No deaths or serious adverse drug reactions were reported in either the 125 mg group or placebo group, and the incidence of serious adverse events between the 2 arms was comparable, according to the study abstract.
"The critical evaluation and discussion of these Phase 3 study results by the leaders of the scientific community at CROI will help to advance our ensitrelvir clinical program as we seek to continue to pursue our objective of making this COVID-19 treatment available for more people worldwide,” said coauthor Isao Teshirogi, PhD, in the press release. “These results are encouraging, and we will continue to investigate the efficacy and safety of ensitrelvir across a range of COVID-19 patient populations.”
In addition, researchers presented exploratory data (not included as primary or secondary endpoints) from the phase 3 part of the study that examined the potential of ensitrelvir to have an effect on long COVID-19 symptoms. Symptoms of long COVID-19 were analyzed at 3 and/or 6 months after initiating treatment with ensitrelvir within 5 days of symptoms onset.
Findings showed that in a subpopulation of patients who self-reported a high score for 14 COVID-19 symptoms at baseline, the overall risk of the presence of long COVID-19—defined for the purpose of the study as at least 2 consecutive reports of the same symptom from among these 14 symptoms as of the time of the last available patient diary—in the 125 mg group significantly decreased compared with placebo (14.5% and 26.3% reported consecutive symptoms in the 125 mg and placebo groups, respectively, 45% relative risk reduction; P<.05).
“A treatment addressing the symptoms of long COVID remains one of the largest unmet needs of the pandemic. An antiviral for this condition would be a welcome addition to the tools we have to care for patients with COVID-19,” said Amesh Adalja, MD, an infectious disease physician and Senior Scholar at the Johns Hopkins Center for Health Security, who was not part of the current study, in the press release. "As these data are from an exploratory analysis, this promising signal will hopefully be followed up with further evaluation of ensitrelvir for long COVID.”
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