Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19, 2024, Can et al

Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19

Abstract

BACKGROUND
Simnotrelvir is an oral 3-chymotrypsin–like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial.

METHODS
In this phase 2–3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19–related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed.

RESULTS
A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of 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 [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, −35.8 hours [95% CI, −60.1 to −12.4]; P=0.006 by Peto–Prentice test). 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 milliliter; 95% CI, −1.79 to −1.24). 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.

CONCLUSIONS
Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176. opens in new tab.)

https://www.nejm.org/doi/full/10.1056/NEJMoa2301425

 

Of course there will be differences I'm not able to comprehend, but at a first glance this essentially seems like a chinese version of Paxlovid, a 3CL inhibitor boosted by ritonavir (there's an abundance of other similar antivirals https://www.sciencedirect.com/science/article/pii/S0166354222001887), that is administered every 12h for 5 days. Due to the far lower price in comparison to Paxlovid it has already become the most popular Covid medication in China.

The company producing the drug is apparently known for producing widely accessible generic pharmaceuticals in China, however in this case Simnotrelvir appears to be a nirmatrelvir derivative that acts very similar https://www.nature.com/articles/s41467-023-42102-y and hence global approval could be possible.