Journal Article

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

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


Nirmatrelvir-ritonavir, also known as Paxlovid, shows efficacy in reducing hospitalization and death from COVID-19 and is approved for such use in the United States. However, its numerous drug interactions pose challenges in certain patients, such as my geriatric patient recently diagnosed with COVID-19. This very recent double-blind, randomized, placebo-controlled trial sought to investigate the efficacy of Simnotrelvir-ritonavir, a protease inhibitor combination similar to Paxlovid with fewer drug interactions.

This study assigned patients who had mild-to-moderate COVID-19 with onset of symptoms within the past 3 days to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The results indicate that a 5-day course of simnotrelvir-ritonavir led to a 1.5-day reduction in the time to symptom resolution, and none of the participants progressed to severe disease or died by day 29. This drug has received emergency approval in China and it will be interesting to see if it is approved in the U.S. given its apparent efficacy and preferred drug interaction profile.