Oral Simnotrelvir May Shorten Recovery Time of Patients With Mild-to-Moderate COVID-19


Patients who received oral simnotrelvir recovered up to 1.5 days faster from COVID-19 compared to patients who received a placebo in the new study.

Oral simnotrelvir may potentially reduce the time it takes for adults with mild-to-moderate COVID-19 to recover, according to findings published in the New England Journal of Medicine.1

Investigators of the new study reported several key findings, including a notable 1.5-day faster recovery time from COVID-19 among participants who received simnotrelvir compared to those who received a placebo.

Although drugs like nirmatrelvir and ensitrelvir that target the SARS-CoV-2 3-chymotrypsin-like cysteine protease enzyme (3CLpro) exist, investigators highlighted the need for more drug options to ease the financial and distributional burdens associated with them. One such option may be simnotrelvir, an antiviral agent that also targets the SARS-CoV-2 3CLpro and has demonstrated promise in a prior phase 1B trial whereby it was associated with a faster decrease in viral load.

To assess the potential benefits of oral simnotrelvir for treating mild-to-moderate COVID-19 in adults, investigators conducted a phase 2/3, double-blind, randomized, placebo-controlled trial (NCT05506176). This trial evaluated the safety and efficacy profile of oral simnotrelvir in combination with ritonavir.

A total of 1208 patients from research sites in China who were at least 18 years of age and showed signs or symptoms of COVID-19 within 3 days before the first dose of trial drug or placebo were included in the final analysis. These patients were randomly assigned to receive either 750 mg of oral simnotrelvir (2 tablets, 375 mg per tablet) plus 100 mg of ritonavir or matching placebo twice daily for 5 days. Patients were monitored for 29 days after the first dose.

Eleven items were used by patients to assess the severity of their COVID-19 signs and symptoms on a 4-point scale (0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). The most frequent symptoms recorded at baseline were sore or dry throat (76.2%), cough (73.4%), and stuffy or runny nose (55.9%).

The primary efficacy end point was the time to sustained resolution of symptoms, defined by investigators as the time from the first dose to the time when all 11 COVID-19-related symptoms were rated as absent by patients for 2 consecutive days. Safety and virology effects were also measured.

Compared to the placebo group, the simnotrelvir group experienced a far shorter median time to sustained resolution of COVID-19 symptoms (ie, symptom scores of 0) which amounted to a difference of about 1.5 days. Similarly, the simnotrelvir group experienced less median time to sustained alleviation of symptoms (ie, symptom scores of ≤ 1) than the placebo group (120.4 hours; 95% CI, 119.4 to 132.8 hours vs 168.3 hours; 95% CI, 155.0 to 191.2 hours.

Further, participants in the simnotrelvir group experienced a greater decrease in viral load, sustained until day 9, than the placebo group. The largest antiviral effect was observed on day 5, whereby the decrease in the simnotrelvir group measured at 1.51 log10 copies per milliliter greater than in the placebo group.

Although the incidence of adverse events was higher in the simnotrelvir group than in the placebo groups, most were mild or moderate. As such, investigators concluded that there were no evident safety concerns associated with the antiviral.

Study limitations exist, investigators noted, and include the possibility of unblinding due to the unique taste of ritonavir and the generally young demographic of participants, among others. In the future, the efficacy and safety of oral simnotrelvir should be evaluated among older patients.

1. Cao B, Wang Y, Lu H, et al. Oral simnotrelvir for adult patients with mild-to-moderate COVID-19. N Engl J Med. 2024;390(3):230-241. doi:10.1056/NEJMoa2301425
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