VV116 noninferior to nirmatrelvir-ritonavir for sustained recovery in COVID-19 patients

1. VV116 is noninferior compared to nirmatrelvir-ritonavir for achieving sustained recovery in mild-to-moderate coronavirus disease 2019 (COVID-19) cases. 

2. Participants in the VV116 group experienced fewer adverse events compared to participants in the nirmatrelvir-ritonavir group within the 28-day study period.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Nirmatrelvir-ritonavir is an antiviral treatment that received widespread authorization for emergency use for the treatment of COVID-19. VV116 is a deuterated remdesivir hydrobromide shown to have potent activity against SARS-CoV-2. In this study comparing VV116 to nirmatrelvir-ritonavir for the treatment of COVID-19, sustained clinical recovery occurred at similar rates in both the nirmatrelvir-ritonavir and VV116 groups. No participants died or progressed to severe COVID-19 by the end of the study. The median time from randomization to sustain resolution of COVID-19-related symptoms was the same in both groups. The time to the first negative SARS-CoV-2 test was similar between groups. Fewer participants in the VV116 group experienced adverse events than in the nirmatrelvir-ritonavir group. None of the three serious adverse events were attributed to the assigned treatment. The most common adverse events were dysgeusia, hypertriglyceridemia, and hyperlipidemia. The strength of this study is that the patient population represented the general population with regard to vaccination status, and the efficacy was similar in subgroup analyses of both vaccinated and unvaccinated populations. A limitation of the study is that the patient population was likely infected with the omicron variant, which may limit the application of these treatments to this specific variant.

Click to read the study in NEJM

Relevant Reading: Oral Nirmatrelvir for high-risk, nonhospitalized adults with Covid-19

In-Depth [randomized controlled trial]: This multicenter, observer-blinded, randomized controlled trial examined the efficacy of oral VV116 compared to oral nirmatrelvir-ritonavir for symptomatic participants at high risk for progression to severe COVID-19. The inclusion criteria were adults age 18 years of age or older, mild-to-moderate COVID-19, positive SARS-CoV-2 reverse-transcriptase-polymerase-chain-reaction test, and at least one risk factor for severe COVID-19. A total of 822 participants were randomized into the study, with 411 participants in each treatment group. Sustained clinical recovery occurred in 377 patients in the VV116 group and 378 participants in the nirmatrelvir-ritonavir group. The hazard ratio for the time from randomization to sustained clinical recovery was 1.17 (95% Confidence interval [CI], 1.01 to 1.35). Similar results were reported in sensitivity analyses with the imputation of missing endpoint data (Hazard Ratio, 1.17; 95% CI, 1.01 to 1.35). The median time from randomization to sustain resolution of symptoms was seven days (95% CI, 7 to 8) in both groups. The median time to the first negative SARS-CoV-2 test was seven days in both groups (Hazard Ratio, 0.99; 95% CI, 0.85 to 1.14). Fewer participants in the VV116 group experienced adverse events than in the nirmatrelvir-ritonavir group (67.4% vs. 77.3%). The most common adverse events were dysgeusia, hypertriglyceridemia, and hyperlipidemia. The most serious adverse events were acute cerebral infarction and deterioration of interstitial lung disease in the nirmatrelvir-ritonavir group and repeat positive for SARS-CoV-2 in the VV116 group. In summary, VV116 was noninferior to nirmatrelvir-ritonavir in treating COVID-19 in high-risk patients.

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