VV116 Pharmacokinetics & Safety in Mild/Moderate Hepatic Impairment – COVID-19 Study
A new study published in February 2026 offers encouraging news for individuals with mild to moderate liver impairment who may require treatment with VV116 (Mindvy, JT001), an oral antiviral medication developed for COVID-19. Researchers found that liver dysfunction did not significantly alter how the body processes the drug, suggesting that dose adjustments are likely unnecessary for this patient population.
Understanding VV116 and the Importance of Liver Function
VV116 is a deuterated form of remdesivir hydrobromide, meaning it’s a chemically modified version of an existing antiviral drug. Deuteration—replacing certain hydrogen atoms with deuterium, a heavier isotope of hydrogen—can sometimes improve a drug’s properties, such as its stability and how long it remains active in the body. Remdesivir itself has been used to treat COVID-19, and VV116 aims to offer a more convenient oral formulation.
The liver plays a crucial role in metabolizing many medications. Impairment of liver function can therefore affect drug exposure – how much of the drug reaches its target in the body – and potentially lead to altered efficacy or increased risk of side effects. Because of this, the researchers specifically investigated how VV116 behaves in individuals with varying degrees of liver dysfunction.
The Phase 1 Study Design
The study, a Phase 1 clinical trial, involved adults with mild or moderate hepatic impairment, as defined by the Child-Pugh method, and a control group of healthy individuals. Participants received a single 0.3-gram dose of VV116 while fasting. Researchers then collected blood samples over 72 hours to measure the concentration of VV116 and its active metabolite, 116-N1, using a highly sensitive laboratory technique called LC-MS/MS (liquid chromatography-tandem mass spectrometry). This allowed them to assess key pharmacokinetic parameters, including:
- AUC (Area Under the Curve): A measure of the total drug exposure over time.
- Cmax: The maximum concentration of the drug in the bloodstream.
- Tmax: The time it takes to reach the maximum concentration.
- t1/2: The drug’s half-life – the time it takes for the concentration to reduce by half.
Key Findings: Pharmacokinetics Largely Unaffected
The study results indicated that overall drug exposure (AUC) was comparable between individuals with mild and moderate liver impairment and the healthy control group. Specifically, the geometric mean ratios (GMRs) were 94.10% (90% confidence interval: 71.59%-123.68%) for mild impairment, and 97.72% (90% confidence interval: 74.34%-128.44%) for moderate impairment, compared to controls. This suggests that the extent of drug absorption did not differ significantly across the groups.
Median Tmax and t1/2 were also similar across all three groups, indicating that the rate at which the drug was absorbed and eliminated was not substantially affected by liver impairment. However, Cmax—the peak drug concentration—was somewhat lower in both impairment cohorts. The clinical significance of this finding is not fully clear, but researchers did not consider it to be a major concern.
Safety Profile Remains Favorable
Treatment-emergent adverse events (side effects that occurred during the study) were reported in 12.5% of participants with mild liver impairment, 37.5% of those with moderate impairment, and 12.5% of the control group. Importantly, all reported events were mild or moderate in severity, transient (temporary), and resolved without any specific treatment. The higher incidence of adverse events in the moderate impairment group was not deemed clinically meaningful, as these events appeared to be isolated and not directly related to VV116 exposure.
Notably, there were no serious adverse events, deaths, or study discontinuations reported in any of the groups.
Implications for Clinical Practice
The findings of this Phase 1 study are reassuring. They suggest that VV116’s pharmacokinetic profile is not substantially altered by mild to moderate hepatic impairment, and that dose adjustments are likely not necessary for patients with these conditions. This is important because it simplifies treatment protocols and avoids the need for complex dose calculations in a vulnerable patient population.
However, it’s important to remember that this was a Phase 1 study, involving a relatively small number of participants. Further research, including larger clinical trials, is ongoing to evaluate the efficacy and safety of VV116 in a broader range of patients with COVID-19. A clinical trial (NCT05582629) is currently underway to evaluate the efficacy and safety of JT001 (VV116) in participants with mild to moderate COVID-19.
a separate case report highlights the need for careful dose determination in patients with severe liver dysfunction. This suggests that while mild to moderate impairment doesn’t necessitate dose adjustments, more significant liver disease may require a more individualized approach.
As of , the World Health Organization and Johns Hopkins University continue to monitor the COVID-19 pandemic, and the development of effective antiviral treatments remains a priority.