Real-world effectiveness and safety of simnotrelvir/ritonavir for COVID-19: A nationwide, multicenter, prospective, observational cohort study in China.

Background: Simnotrelvir has demonstrated potent anti-viral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In a Phase II/III study, Simnotrelvir plus ritonavir (S/R, co-packaged) shortened the time to the resolution of symptoms in adult COVID-19 patients. However, real-world data on effectiveness of simnotrelvir/ritonavir against SARS-CoV-2 during XBB variant surges are still limited.

Study Design And Methods: This was a nationwide, multicenter, prospective, observational real-world study at 42 sites in China. Adult patients with mild to moderate COVID-19 and at disease onset were eligible for participation. Patients were grouped in S/R group (treated with S/R) and control group (not receiving oral antivirals for COVID-19). The primary endpoint was the COVID-19-related hospitalization or all-cause mortality within 28 days. Secondary endpoints included the time from confirmed SARS-CoV-2 infection to negative conversion, and the time to resolution of COVID-19 symptoms. Besides, serious adverse events (SAE), adverse drug reactions (ADR) and combined medication were reported. Propensity Score-Matched (PSM) analysis (1:1) was performed for adjustment for baseline variables. Hazard ratios (HR) and adjusted risk ratios (aRR) were estimated using the Cox and Modified Poisson regression, respectively.

Results: Between June 6, 2023, and December 27, 2023, 3522 patients were enrolled. S/R was associated with a reduced incidence of COVID-19-related hospitalization (6/1896 [0.3%] vs. 43/1408 [3.1%]; HR: 0.110, 95% confidence interval [CI]: 0.043 to 0.283, p < 0.001 vs control), consistently with the results after PSM (4/1381 [0.3%] in S/R vs. 40/1381 patients [2.9%]; aRR: 0.12; 95% CI: 0.05, 0.29; P < 0.001). No deaths occurred in both S/R and control groups. Matched Patients over 65 and patients with risk factors who received S/R achieved significantly reduced risk of COVID-19-related hospitalization (aRR: 0.032; 95% CI: 0.004, 0.268; aRR: 0.034; 95% CI: 0.005, 0.252, respectively; all P < 0.001). Furthermore, S/R shortened the median time to viral clearance by 1 day (6.0 vs 7.0 days; 95% CI: -2.0 to -1.0; P < 0.001) and reduced the median time to symptom resolution by 2 days (8.0 days vs 10.0 days; 95% CI: -2.0 to -1.0; P < 0.001). Besides, the proportion of patients in the S/R group using combined medication was significantly lower than that in the control group (30.2% vs 49.4%). Subgroup analysis showed potential protective effect of S/R in the elderly and patients with more than 1 risk factor.

Conclusion: In real world, S/R significantly reduced the incidence of COVID-19-related hospitalization, demonstrated favorable safety profiles, and less use of combined medication.