Casirivimab / Imdevimab (2) – Ronapreve®

• Clinical trials
  • The COV-2067 trial is an adaptive, placebo-controlled, double-blind, randomised Phase 1/2/3 trial investigating treatment with casirivimab/imdevimab in patients with COVID-19.

a) Adults and adolescents aged 12 years and over, weighing at least 40 kg, with COVID-19 who do not require additional oxygen therapy and who are at increased risk of a severe course of COVID-19 following infection with a viral variant against which Casirivimab/Imdevimab has no sufficient efficacy

• For the treatment of adult and adolescent patients with COVID-19 who do not require additional oxygen therapy, who are at increased risk of severe COVID-19, and who are infected with a viral variant against which casirivimab/Imdevimab has no sufficient efficacy.
• For adults and adolescents infected with a SARS-CoV-2 variant for which, either demonstrably or based on the current pandemic situation, Casirivimab/Imdevimab, no conclusion can be drawn regarding the additional benefit of treating COVID-19 with Casirivimab/Imdevimab.
• For this patient population (patient population a), the additional benefit of casirivimab/imdevimab compared with the appropriate comparator therapy is not proven.

b) Adults with COVID-19 who do not require additional oxygen therapy and who are at increased risk of a severe course of COVID-19 following infection with a viral variant against which Casirivimab/Imdevimab demonstrates sufficient efficacy

• For the treatment of adult patients with COVID-19 who do not require additional oxygen therapy, who are at increased risk of severe COVID-19, and who are infected with a viral variant against which Casirivimab/Imdevimab has sufficient efficacy, there is a hint of considerable additional benefit of Casirivimab/Imdevimab compared with the appropriate comparator therapy.
• Overall, for adults infected with a viral variant against which casirivimab/imdevimab demonstrates sufficient efficacy, there is a hint of a considerable additional benefit of casirivimab/imdevimab.
• mortality
  • For the endpoint of overall mortality, there is a statistically significant advantage for casirivimab/imdevimab compared to the other treatment groups.
• Morbidity – Hospitalisation due to COVID-19
  • The study documentation and the information provided by the pharmaceutical manufacturer do not specify the conditions under which hospitalisation due to COVID-19 occurred. Furthermore, it remains unclear whether hospitalisation was subject to a minimum duration criterion, such as a minimum of 24 hours.
  • For the endpoint of hospitalisation due to COVID-19, there is a statistically significant advantage for casirivimab/imdevimab compared to the other treatment groups.
• Morbidity – admission to an intensive care unit due to COVID-19
  • For the endpoint of admission to an intensive care unit due to COVID-19, there was no statistically significant difference between the treatment groups.
• Morbidity – Resolution of COVID-19 symptoms (SE-C19)
  • COVID-19 symptoms were assessed in the COV-2067 study using the SE-C19 questionnaire.
  • For the endpoint ‘resolution of COVID-19 symptoms’, assessed using the SE-C19 questionnaire, there was a statistically significant advantage for casirivimab/imdevimab among the treatment groups.
  • However, there is an effect modification by the characteristic of age. For patients aged 18 to 64, there is no hint of additional benefit from casirivimab/imdevimab compared with treatment as clinically indicated. For patients aged 65 and over, however, there is a hint of an additional benefit of casirivimab/imdevimab compared with treatment as clinically indicated.
• Morbidity – return to normal health, return to normal activities and health status (EQ-5D VAS)
  • No usable data are therefore available for the endpoints ‘return to normal health’, ‘return to normal activities’ and ‘health status’ as assessed using the EQ-5D VAS.
• quality of life
  • Endpoints relating to health-related quality of life were not assessed in the included study.
• Side effects – severe adverse events (SAEs), severe adverse events (AEs), discontinuations due to AEs and infusion-related reactions
  • No usable data are available for the endpoints in the ‘side effects’ category.
  • When recording SUEs and severe UEs, disease-related events were also captured in the COV-2067 study.
  • However, based on the results regarding common SUEs and severe AEs, and given the minor proportion of patients experiencing such events, no adverse effects of casirivimab/imdevimab are expected to the extent that they could call into question the additional benefit of casirivimab/imdevimab.
• 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 casirivimab/imdevimab.
  • In the morbidity category, statistically significant advantages in favour of casirivimab/imdevimab compared with the control arm were observed for the endpoints of hospitalisation due to COVID-19 and resolution of COVID-19 symptoms, as assessed using SE-C19.
  • For the additional endpoint in the morbidity category – admission to an intensive care unit due to COVID-19 – there was no statistically significant difference between the treatment groups.
  • No usable data are available for the morbidity endpoints ‘return to normal health’, ‘return to normal activities’ and ‘health status’ (EQ-5D VAS).
  • Endpoints relating to health-related quality of life were not assessed in the study.
  • No usable data are available for the endpoints in the ‘side effects’ category. However, based on the results regarding common SUEs and severe AEs, and given the minor proportion of patients experiencing such events, no adverse effects of casirivimab/imdevimab are expected to such an extent that they could call into question the additional benefit of casirivimab/imdevimab.
  • In summary, positive effects are evident in the categories of mortality and morbidity, which are not offset by any negative effects.
  • In summary, for adults with COVID-19 who do not require additional oxygen therapy and who are at increased risk of a severe course of COVID-19, there is a hint of considerable additional benefit from casirivimab/Imdevimab compared with the appropriate comparator therapy, i.e. treatment as clinically indicated.

c) Adolescents aged 12 years and over weighing at least 40 kg with COVID-19 who do not require additional oxygen therapy and who are at increased risk of a severe course of COVID-19, in the event of infection with a viral variant against which casirivimab/Imdevimab has demonstrated sufficient efficacy

• For the treatment of adolescent patients with COVID-19 who do not require additional oxygen therapy, who are at increased risk of a severe course of COVID-19, and who are infected with a viral variant against which Casirivimab/Imdevimab demonstrates sufficient neutralising activity, the additional benefit is not proven.
• No data are available for adolescents aged 12 to < 18 years weighing at least 40 kg who do not require additional oxygen therapy and who are at increased risk of a severe course of COVID-19 (see study description for patient population b).
• The additional benefit of casirivimab/imdevimab for this age group is therefore not proven.

Courtesy translation only, please refer to the German original.