Nirmatrelvir / Ritonavir (1) – Paxlovid®

• Clinical trials
  • The EPIC-HR trial is a placebo-controlled, double-blind, randomised trial investigating outpatient treatment with nirmatrelvir/ritonavir in adult patients in the early stages of COVID-19 who had ≥ 1 risk factor for a severe course of COVID-19.

Adults with COVID-19 who do not require supplemental oxygen and are at increased risk of developing severe COVID-19

• Hint for a considerable additional benefit
• Overall, there is a hint of considerable additional benefit from nirmatrelvir/ritonavir compared with treatment as clinically indicated.
• mortality
  • For the endpoint ‘all-cause mortality’, a statistically significant advantage was observed between the treatment groups in favour of nirmatrelvir/ritonavir.
• Morbidity – Severe COVID-19
  • For the endpoint ‘severe COVID-19’, a statistically significant advantage was observed between the treatment groups in favour of nirmatrelvir/ritonavir.
  • In the EPIC-HR study, the endpoint ‘severe COVID-19’ was operationalised as > 24 hours of acute care in a hospital or similar acute care facility. For the present benefit assessment, the endpoint ‘severe COVID-19’ is operationalised as hospitalisation due to COVID-19.
• Morbidity – need for intensive care due to any cause
  • For the endpoint ‘need for intensive care due to any cause’, there is a statistically significant advantage for nirmatrelvir/ritonavir compared to the other treatment groups.
• Morbidity – Relief of COVID-19 symptoms by day 28
  • For the endpoint ‘relief of COVID-19 symptoms by day 28’, there is a statistically significant advantage for the treatment group that receives nirmatrelvir/ritonavir.
• Morbidity – COVID-19 symptoms at week 24
  • For the endpoint ‘COVID-19 symptoms at week 24’, there was no statistically significant difference between the treatment groups.
• Morbidity – Impairment of activity (WPAI-COVID-19), health status (EQ-5D VAS)
  • For both endpoints, the response rates at the start of the survey were very low, at around 3 % in each case. Although the response rates increased at later survey time points, they remained at a low level of below 45% in each case. Consequently, only very few patients were included in the analyses, meaning that no usable data is available for the benefit assessment.
• quality of life
  • Endpoints relating to health-related quality of life were not assessed in the EPIC-HR study.
• Side effects
  • No usable data are available for endpoints in the ‘side effects’ category.
  • However, based on the results regarding common SAEs, severe SAEs and discontinuations due to SAEs, no adverse effects of nirmatrelvir/ritonavir are expected to such an extent that they could call into question the additional benefit of nirmatrelvir/ritonavir.
• Overall assessment
  • In the mortality category, a statistically significant advantage was observed between the treatment groups for the endpoint of all-cause mortality, in favour of nirmatrelvir/ritonavir.
  • In the morbidity category, statistically significant benefits in favour of nirmatrelvir/ritonavir were observed for the endpoints ‘severe COVID-19’, ‘need for intensive care for any cause’ and ‘relief of COVID-19 symptoms by day 28’, there were statistically significant advantages in favour of nirmatrelvir/ritonavir compared with the control arm.
  • For the additional endpoint in the morbidity category, ‘COVID-19 symptoms at week 24’, no statistically significant difference was observed between the treatment groups.
  • No usable data are available for the morbidity endpoints “impaired activity (WPAI-COVID-19)” and “health status (EQ-5D VAS)”.
  • Endpoints for the health-related quality of life category were not assessed in the study.
  • In summary, positive effects are evident in the categories of mortality and morbidity, with no adverse effects to counterbalance them. An overall assessment of the results, based on the positive effects observed in the endpoints ‘all-cause mortality’, ‘severe COVID-19’, ‘need for intensive care due to any cause’ and ‘relief of COVID-19 symptoms by day 28’, a considerable additional benefit is inferred compared with standard medical care.

Courtesy translation only, please refer to the German original.