Phase III trial of VV 116 in COVID-19 published in NEJM.- Shanghai Junshi Biosciences

The study, led by Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, is the first “head-to-head” phase III clinical study of small molecule oral anti-SARS-CoV drug in Chinese COVID-19 patients during the Omicron outbreak. The results indicated that the primary endpoint of the study realized the designed noninferiority endpoint, and VV116 group had a shorter time to sustained clinical recovery with less safety concerns as compared with PAXLOVID.

A total of 771 patients (Full Analysis Set, FAS) were treated with VV 116 (n = 384) or PAXLOVID (n = 387). Among them, the median age of FAS patients was 53 (range: 18-94), 50.2% of them were female, 92.1% of them had mild COVID-19, 75.7% of them were fully vaccinated or boosted, and 77.3% of them received VV 116 or PAXLOVID therapy within 5 days after symptom onset. The most common high-risk factors in patients were: age at least 60 years (37.7%), cardiovascular disease including hypertension (35.1%), obesity or overweight BMI at least 25 (32.9%), current smoking (12.5%), and diabetes (10.1%). The primary end point of the study was the time from randomization to sustained clinical recovery, with a lower boundary of the two-sided 95% confidence interval (CI) for the hazard ratio (HR) > 0.8 defined as noninferiority. Secondary efficacy end points included the proportion of patients who progressed to severe or critical COVID-19 or death from any cause by Day 28, the change in COVID-19 related symptom score and the score on the WHO Clinical Progression Scale, time to sustained resolution of all target symptoms, and to a first negative SARS-CoV-2 test. Safety endpoints included adverse events (AEs) and serious adverse events (SAEs). According to the final analysis (as of August 18, 2022), VV 116 and PAXLOVID achieved noninferiority in the “time to sustained clinical recovery” in the FAS population (HR = 1.17, 95% CI: 1.02~1.36), and the median time to sustained clinical recovery was shorter in the VV116 group than that in the PAXLOVID group (4 days vs. 5 days).

For VV 116 group and PAXLOVID group, they showed similar results in respect of “time to sustained resolution of all target symptoms” and “time to a first negative SARS-CoV-2 test”, with a median time of 7 days. At each preset time point (Days 5, 7, 10, 14, and 28), the proportion of patients with clinical recovery was larger in the VV116 group than that in the PAXLOVID group. No patients in either group hase progression to severe/critical COVID-19 or had died. In addition, about 3/4 of the patients in this study had vaccinated against SARS-CoV-2, and such patients have been excluded from most trials, and subgroup analysis showed that there was no statistically significant difference in the treatment results between VV 116 and PAXLOVID in the vaccinated or unvaccinated population. VV 116 showed fewer safety concern than PAXLOVID. The incidence of AEs in VV 116 group was lower than that in the PAXLOVID group (all-grade AEs: 67.4% vs. 77.3%, Grade 3 or 4 AE: 2.6% vs. 5.7%).

See: "VV116 versus Nirmatrelvir–Ritonavir for Oral Treatment of Covid-19" Zhujun Cao et al. NEJM December 28, 2022 DOI:10.1056/NEJMoa2208822