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An oral remdesivir analogue (VV116) was just as good as nirmatrelvir-ritonavir (Paxlovid) for the treatment of mild-to-moderate COVID-19 in adults at risk for severe disease, and may be safer, results of a phase III trial from China suggested.

Sustained clinical recovery of COVID-19 symptoms with a 5-day course of VV116 proved noninferior to nirmatrelvir-ritonavir, with patients recovering at a median 4 days versus 5 days, respectively, from the start of treatment (HR 1.17, 95% CI 1.02-1.36), according to Ren Zhao, MD, PhD, of Shanghai Jiao Tong University School of Medicine, and colleagues.

Among more than 800 randomized patients, none progressed to severe COVID-19 or died during the study, which was conducted during a period of Omicron B.1.1.529 predominance.

Although remdesivir (Veklury) is a recommended option for individuals with high-risk COVID, it needs to be administered intravenously over the course of 3 days, "which limits its widespread use during the pandemic," the researchers explained in the .

VV116, meanwhile, "is a deuterated remdesivir hydrobromide with oral bioavailability and potent activity against SARS-CoV-2 in studies in animals and satisfactory safety and side-effect profiles in phase I trials," the group wrote.

Supply of nirmatrelvir-ritonavir has not kept pace with global demand, according to Zhao and co-authors, and the effectiveness of nirmatrelvir depends on ritonavir, "which has multiple drug-drug interactions warranting specialized assessment before prescription."

Through 28 days, fewer adverse events (AEs) were reported in the VV116 group (67.4% vs 77.3% with nirmatrelvir-ritonavir), and grade 3/4 AEs were half as frequent (2.6% vs 5.7%, respectively). Less frequent AEs with VV116 included dysgeusia (3.6% vs 25.8% with nirmatrelvir-ritonavir), hypertriglyceridemia (10.7% vs 20.9%), and hyperlipidemia (3.1% vs 9.6%).

Both drugs performed similarly for time to sustained clinical recovery (score of 0-1 for each of 11 symptoms on a 0-3 scale), but the proportion was higher with VV116 compared with nirmatrelvir-ritonavir at each time point:

• Day 5: 66.4% vs 57.6%, respectively
• Day 10: 94.3% vs 92%
• Day 28: 98.4% vs 97.7%

Similar rates of complete symptom resolution and SARS-CoV-2 clearance were reported at each time point.

The study was performed from April 4 to May 2. Of the 997 participants screened for inclusion to the trial from seven hospitals in Shanghai, 822 were randomized for treatment with either VV116 (600 mg every 12 hours on day 1, then 300 mg every 12 hours from day 2 to 5) or nirmatrelvir-ritonavir (300 mg and 100 mg, respectively, every 12 hours for 5 days).

After discontinuations, non-adherence, non-administration, and other exclusions, 771 were included in the final analysis and completed the 28-day assessments.

Three-fourths of the participants were vaccinated, with 45% having received a booster dose as well. In subgroup analysis according to vaccination status, researchers saw similar results in both vaccinated and unvaccinated participants.

Demographic and clinical characteristics were similar between the two groups. The median age was 53, and nearly all identified as Han ethnicity.

Risk factors for severe illness included age 60 and over (37.7%), cardiovascular disease (35.1%), obesity (32.9%), being a smoker (12.5%), diabetes (10.1%), chronic lung disease (5.7%), cancer (4.2%), and chronic kidney disease (1.4%). One patient in the nirmatrelvir-ritonavir group was immunosuppressed.

Limitations included the lack of a placebo group and of a diverse participation.

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