Simnotrelvir and ritonavir combo may shorten time to symptom resolution in patients with COVID-19: NEJM

"In the trial of treatment for mild-to-moderate COVID-19, simnotrelvir plus ritonavir shortened the time to sustained symptom resolution by about 1.5 days among patients who received treatment within 3 days after symptom onset," the researchers reported.

Simnotrelvir imparted more benefits for the alleviation of respiratory symptoms than a placebo. Also, simnotrelvir was associated with an additional decrease in viral load until day 9. On day 5, the most pronounced antiviral effect occurred when the reduction in viral load in the simnotrelvir group was 1.51 log10 copies per millilitre higher than in the placebo group. Most adverse events were mild or moderate.

The ongoing coronavirus disease 2019 pandemic continues to inflict an important burden on healthcare systems and global health. The effect of the disease on high-risk groups can be lessened by vaccination but is less effective in preventing infections caused by emerging SARS-CoV-2 variants with strong immune evasion. There is a need for effective antiviral agents for treating SARS-CoV-2 infections.

Numerous small-molecule drugs (e.g., ensitrelvir5 and nirmatrelvir4) are available that target the SARS-CoV-2 3-chymotrypsin–like cysteine protease enzyme (3CLpro, also known as main protease [Mpro]). However, more drug options are needed to accelerate the resolution of symptoms among patients with mild-to-moderate COVID-19 because of the high costs of the drugs and inequity in their distribution.

Simnotrelvir is an oral 3-chymotrypsin–-like protease inhibitor that has been reported to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. Bin Cao, Central People's Hospital of Zhanjiang, Zhanjiang, China, and colleagues conducted a phase 2–3, double-blind, randomized, placebo-controlled trial to determine the safety and efficacy of simnotrelvir plus ritonavir in the treatment of adult patients with mild-to-moderate Covid-19.

1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir, and 605 to placebo.

Based on the study, the researchers reported the following findings:

• Among patients in the modified intention-to-treat population who received the first dose of a trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of COVID-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours versus 216.0 hours).
• On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per millilitre).
• The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%).
• Most adverse events were mild or moderate.

"The findings showed that early administration of simnotrelvir plus ritonavir was effective in shortening the time to symptom resolution among adult patients with COVID-19, without evident safety concerns," the researchers concluded.

Reference:

Cao B, Wang Y, Lu H, Huang C, Yang Y, Shang L, Chen Z, Jiang R, Liu Y, Lin L, Peng P, Wang F, Gong F, Hu H, Cheng C, Yao X, Ye X, Zhou H, Shen Y, Liu C, Wang C, Yi Z, Hu B, Xu J, Gu X, Shen J, Xu Y, Zhang L, Fan J, Tang R, Wang C. Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19. N Engl J Med. 2024 Jan 18;390(3):230-241. doi: 10.1056/NEJMoa2301425. PMID: 38231624.