The race to find effective COVID-19 treatments continues, and a new contender has emerged. A recent clinical trial reveals promising results for the antiviral drug ensitrelvir, potentially offering a more accessible and affordable option for patients worldwide. But is it too good to be true?
According to a Phase 2 trial published in The Lancet Infectious Diseases, ensitrelvir, a once-daily oral drug developed by Shionogi, shows potent antiviral activity against COVID-19. This drug is already registered and widely used in Japan and Singapore, with over 1 million people having received it. However, its effectiveness outside these countries remains under investigation.
The trial aimed to compare ensitrelvir with ritonavir-boosted nirmatrelvir (Paxlovid), the first oral antiviral approved by the FDA for COVID-19. Paxlovid has become a go-to medication for mild-to-moderate COVID-19 cases, but its high cost, numerous contraindications, and limited availability outside wealthy nations present significant challenges.
The study, conducted in Thailand and Laos, involved low-risk outpatients aged 18-60 with early symptomatic COVID-19. Researchers measured viral clearance rates to assess the drugs' efficacy, as COVID-19's milder nature has reduced the occurrence of severe outcomes like hospitalization and death, making these hard endpoints less practical for comparison.
And here's where it gets interesting: both ensitrelvir and ritonavir-boosted nirmatrelvir accelerated viral clearance significantly. By day 3, viral densities were 2.9 times lower in the ensitrelvir group and 2.4 times lower in the ritonavir-boosted nirmatrelvir group compared to the no-drug group. By day 5, viral clearance rates were 82% faster with ensitrelvir and 116% faster with ritonavir-boosted nirmatrelvir. However, in a non-inferiority comparison, ensitrelvir's viral clearance was 16% slower than nirmatrelvir.
Not only did the drugs speed up viral clearance, but they also led to faster symptom resolution: 32% faster in the ensitrelvir group and 38% faster in the ritonavir-boosted nirmatrelvir group. Viral rebound was rare, occurring in 7% of the nirmatrelvir group and 5% of the ensitrelvir group, with no patients developing severe disease.
A meta-analysis further supports these findings, showing that ensitrelvir and ritonavir-boosted nirmatrelvir had the largest antiviral effects among various small-molecule drugs tested in the trial, including remdesivir and molnupiravir.
But what sets ensitrelvir apart? The authors highlight its advantages over Paxlovid, such as a lower pill burden (one pill per day vs. two) and a more pleasant taste. Additionally, it could be a viable option for immunocompromised patients who take medications that interact with ritonavir.
As the threat of COVID-19 to the general population diminishes, many may question the need for new antivirals. However, the authors caution that more virulent variants could change this perspective. COVID-19 can still pose a significant risk to frail, elderly, or immunocompromised individuals, who may benefit from effective treatments.
The future of ensitrelvir as a COVID antiviral treatment is uncertain, but Shionogi has submitted an NDA to the FDA for its use in COVID-19 prevention, citing a Phase 3 trial that showed a 67% reduced infection risk.
This development raises questions: Is ensitrelvir the next big thing in COVID-19 treatment? Will it be accessible and affordable for those who need it most? And how will it compare to other emerging treatments? The ongoing research and regulatory processes will provide answers, but the potential impact on global health is undeniable.
