The paper presents final analysis results from a multicenter, double-blind, phase 3, randomized controlled study (NCT05582629) evaluating the efficacy and safety of VV116 (mindeudesivir hydrobromide tablets, product code: VV116/JT001) in patients with mild-to-moderate COVID-19. This study demonstrated that VV116 significantly reduced the time to sustained clinical symptom resolution compared to placebo, with no observed safety concerns.

During the study, academician Lanjuan LI, Director of the State Key Laboratory for Diagnosis & Treatment of Infectious Diseases (Zhejiang University), served as the primary investigator and corresponding author. Co-first authors include Prof. Xiaohong FAN and Prof. Yun Ling from Shanghai Public Health Clinical Center, Prof. Xiahong DAI, Prof. Lihua WU and Prof. Lingling TANG from Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College.

Efficacy analyses were conducted on 1296 enrolled adult patients (646 in the VV116 group and 650 in the placebo group), with a median age of 35.0 years, of whom about 43.1% carried high-risk factors for progression to severe COVID-19. According to the SARS-CoV-2 genetic variation evaluated at enrollment, BA.5.2.48 and BF.7.14 were the leading subvariants.

At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1.21, 95% CI 1.04–1.40; p=0.0023). In the final analysis of the study, a substantial reduction in the time to sustained clinical symptom resolution was observed with VV116 compared to placebo (median: 10.9 vs.12.9 days; HR=1.17; 95% CI: 1.04 - 1.33; p=0.0009), consistent with the interim analysis. For the elderly patient subgroup (≥60 years old), the time to sustained clinical symptom resolution was also shorter in the VV116 group compared to the placebo group, with an HR of 1.22 (95% CI: 0.74-2.01), which is consistent with the overall population.

Previously, an active comparator-controlled phase 3 study of VV116 (NCT05341609) published in the New England Journal of Medicine showed that VV116 was non-inferior to nirmatrelvir/ritonavir in reducing the time to sustained clinical symptom resolution among patients with mild-to-moderate COVID-19 at risk for progression (median time: 7 vs. 7 days; HR=1.06; 95% CI: 0.91, 1.22).

By day 5 of the study treatment, compared to the placebo group, a substantial increase in the SARS-CoV-2 Ct value, as well as a more rapid decrease in the viral load, were observed in the VV116 group.

Notably, the efficacy of a 5-day treatment with VV116, including the significant shortening of time to sustained clinical symptom resolution and clinical symptom alleviation in patients, were observed regardless of the presence of high-risk factors for progression to severe COVID-19 or SARS-CoV-2 vaccination status.

VV116 was well-tolerated in patients with mild-to-moderate COVID-19. Among 1347 patients in the safety data set (674 patients in the VV116 group and 673 patients in the placebo group), the incidence of treatment-emergent adverse events (TEAEs) of any grade was similar between groups (35.9% vs. 42.1%). The incidence of treatment-releated adverse events (TRAEs) assessed by the investigator was 17.4% in the VV116 group and 23.2% in the placebo group. Most of the TEAEs were grade 1 or 2. Only 1 patientin the placebo group, progressed to severe COVID-19, and no deaths occurred.

“As of today, more than 3000 patients worldwide are actively participating in our clinical trials for VV116, including several domestic and international phase 3 trials,” said Dr. Jianjun ZOU, Global Research and Development President at Junshi Biosciences, “This extensive participation provides robust data, establishing VV116 as the most evidence-based, domestically-made oral anti-viral medication for COVID-19. Within a single year, VV116 was featured twice in leading international medical journals, which reflected the global recognition of the VV116 R&D team’s research capabilities and R&D quality. We take great pride in these achievements. The rise of innovative domestic COVID-19 treatments stands as a testament to the Chinese pharmaceutical industry’s advancement towards innovation and serves as a commitment to ensuring health and safety for all. Along with our fellow collaborators, Junshi Biosciences will continue onward, propelling further development and benefiting more patients!”