VV116 versus Nirmatrelvir–Ritonavir for Oral Treatment of Covid-19

Abstract

Background Nirmatrelvir–ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short of the global demand, which creates a need for more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We conducted a phase 3, noninferiority, observer-blinded, randomized trial during the outbreak caused by the B.1.1.529 (omicron) variant of SARS-CoV-2. Symptomatic adults with mild-to-moderate Covid-19 with a high risk of progression were assigned to receive a 5-day course of either VV116 or nirmatrelvir–ritonavir. The primary end point was the time to sustained clinical recovery through day 28. Sustained clinical recovery was defined as the alleviation of all Covid-19–related target symptoms to a total score of 0 or 1 for the sum of each symptom (on a scale from 0 to 3, with higher scores indicating greater severity; total scores on the 11-item scale range from 0 to 33) for 2 consecutive days. A lower boundary of the two-sided 95% confidence interval for the hazard ratio of more than 0.8 was considered to indicate noninferiority (with a hazard ratio of >1 indicating a shorter time to sustained clinical recovery with VV116 than with nirmatrelvir–ritonavir). Results A total of 822 participants underwent randomization, and 771 received VV116 (384 participants) or nirmatrelvir–ritonavir (387 participants). 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%). Conclusions Among adults with mild-to-moderate Covid-19 who were at risk for progression, VV116 was noninferior to nirmatrelvir–ritonavir with respect to the time to sustained clinical recovery, with fewer safety concerns. (Funded by Vigonvita Life Sciences and others; ClinicalTrials.gov number, NCT05341609 ; Chinese Clinical Trial Registry number, ChiCTR2200057856.)

Development and validation of a nomogram to predict failure of 14-day negative nucleic acid conversion in adults with non-severe COVID-19 during the Omicron surge: a retrospective multicenter study

“…Nirmatrelvir/ritonavir and VV116, a remdesivir derivative, were included as new oral small-molecule antiviral drugs in our study; the former has an emergency use authorization from the US Food and Drug Administration [ 22 ], while the latter is currently undergoing clinical trials [ 15 , 23 , 24 ]. Ideally, the evaluation of protease inhibition for COVID-19 in high-risk patients (EPIC-HR) trial conducted by Hammond et al showed that early treatment with nirmatrelvir/ritonavir could significantly reduce both the viral load and risk of COVID-19-related hospitalization or death [ 25 ].…”

How to use COVID-19 antiviral drugs in patients with chronic kidney disease

“…The drug had shown its potential against COVID-19 as it reduces lethality by 89%. It has been shown that treatment with nirmatrelvir–ritonavir reduces the risk of hospitalization or progression to severe COVID-19 infection in vaccinated patients with COVID-19 ( Cao et al, 2022 ). The safety profile of nirmatrelvir is promising, as it has mild side effects and does not have dose-dependent toxicity.…”

Use of Oral Antivirals Ritonavir-Nirmatrelvir and Molnupiravir in Patients with Multiple Myeloma Is Associated with Low Rates of Severe COVID-19: A Single-Center, Prospective Study

“…Both molnupiravir and ritonavir/nirmatrelvir have shown to reduce the risk for severe COVID-19, including hospitalization and/or death, compared with placebo in unvaccinated individuals [ 11 , 12 ]. More recent data including vaccinated patients with mild COVID-19 support the early administration of antivirals for preventing severe outcomes [ 13 ]. Although available evidence supports the use of antivirals in patients with SARS-CoV-2 infection to prevent severe disease, relevant data on MM patients are scarce.…”