In a noninferiority trial of adults with mild-to-moderate COVID-19 who were at risk for progression, the oral antiviral agent VV116 was noninferior to nirmatrelvir-ritonavir on efficacy measures and had fewer safety concerns, researchers report. VV116 also has no effects on the cytochrome P-450 drug-metabolizing enzymes or major drug transporters, minimizing interactions with other drugs.
Conducted in Shanghai, China, from March through June 2022, the phase 3, observer-blinded trial included 771 adults who were randomized to a 5-day course of VV116 or nirmatrelvir-ritonavir. Based on a primary endpoint of the time to sustained clinical recovery through day 28, the study shows: “The noninferiority of VV116 to nirmatrelvir–ritonavir with respect to the time to sustained clinical recovery was established in the primary analysis (hazard ratio, 1.17; 95% confidence interval [CI], 1.01 to 1.35) and was maintained in the final analysis (median, 4 days with VV116 and 5 days with nirmatrelvir–ritonavir; hazard ratio, 1.17; 95% CI, 1.02 to 1.36). In the final analysis, the time to sustained symptom resolution (score of 0 for each of the 11 Covid-19–related target symptoms for 2 consecutive days) and to a first negative SARS-CoV-2 test did not differ substantially between the two groups. No participants in either group had died or had had progression to severe Covid-19 by day 28. The incidence of adverse events was lower in the VV116 group than in the nirmatrelvir–ritonavir group (67.4% vs. 77.3%).”
The authors add: “Transient dysgeusia was reported in one quarter of the participants receiving nirmatrelvir–ritonavir in this trial, a proportion higher than that previously reported in the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial (5.6%); this adverse event warrants more attention in future trials. In addition, the incidence of dyslipidemia was relatively high among both nirmatrelvir–ritonavir recipients and VV116 recipients. Although this adverse reaction has been noted with long-term use of ritonavir in patients with human immunodeficiency virus infection, the possible effect of nirmatrelvir or VV116 on lipid metabolism needs further investigation.”