Remdesivir (2) – Veklury®

• Clinical trials
  • The GS9012 trial is a placebo-controlled, double-blind, randomised phase 3 trial investigating outpatient treatment with remdesivir in patients in the early stages 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 minor additional benefit
• Due to these uncertainties, the certainty of the evidence is classified as ‘hint’.
• mortality
  • No deaths occurred during the course of the study.
  • No conclusion regarding additional benefit can be drawn for the mortality category.
• Morbidity – Total hospitalisation
  • For the endpoint ‘total hospitalisation’, there were statistically significantly fewer hospitalisations in the remdesivir arm compared with the control arm.
  • The observed advantage is attributable to hospitalisation due to COVID-19.
  • In the study, hospitalisation was at the discretion of the investigator, and no clear criteria for hospitalisation were specified.
  • Furthermore, the ‘total hospitalisation’ endpoint was not pre-specified.
  • The generalisability of the advantage regarding total hospitalisation and its interpretability within the German healthcare context is complicated by the fact that patients in Germany are admitted to hospital for treatment with remdesivir regardless of their clinical symptoms.
• Morbidity – Hospitalisation due to COVID-19
  • For the endpoint ‘hospitalisation due to COVID-19’, there were statistically significantly fewer hospitalisations in the remdesivir arm compared with the control arm.
  • In the therapeutic indication, patients with mild to moderate disease usually recover whilst in isolation at home, whilst hospitalisation generally only occurs if symptoms worsen due to COVID-19.
  • Therefore, in this case, hospitalisation can be regarded as an approximation of the clinical condition of worsening symptoms.
  • Consequently, the endpoint ‘hospitalisation due to COVID-19’ provides insights into disease-specific morbidity and is used in this specific case.
• Morbidity – need for intensive care due to any cause
  • For the endpoint ‘need for intensive care due to any cause’, there is no statistically significant difference between the treatment groups.
• Health-related quality of life
  • Endpoints relating to health-related quality of life were not assessed in the study.
• Side effects – severe adverse events (SUEs)
  • For the endpoint ‘SUEs’, there was no statistically significant difference between the treatment groups.
• Side effects – severe adverse events (severe AEs)
  • No statistically significant difference was observed between the treatment groups for the ‘severe AEs’ endpoint.
• Side effects – Withdrawal due to adverse events (AEs)
  • There were no discontinuations due to adverse events during the course of the study.
• Overall assessment
  • No deaths occurred during the study. No conclusions regarding additional benefit can be drawn for the mortality category.
  • In the morbidity category, a statistically significant advantage in favour of remdesivir compared with the control arm was observed for the endpoint of total hospitalisation or hospitalisation due to COVID-19.
  • For the additional endpoint in the morbidity category – the need for intensive care for any cause – no statistically significant difference was observed between the treatment groups.
  • Endpoints for the health-related quality of life category were not assessed in the study.
  • In the ‘Side Effects’ category, there were no statistically significant differences between the treatment arms for either the ‘SUEs’ or ‘severe AEs’ endpoints. No patients experienced therapy discontinuation due to side effects during the course of the study.
  • In summary, a positive effect was observed in the morbidity category, whose extent is classified as minor.
• Overall assessment
  • In the overall assessment of the positive effect on total hospitalisation or hospitalisation due to COVID-19, taking into account the uncertainties mentioned, there is a hint of a minor additional benefit.

Courtesy translation only, please refer to the German original.