Sotrovimab (1) – Xevudy®

• Clinical trials
  • The COMET-ICE trial is a placebo-controlled, double-blind, randomised trial investigating outpatient treatment with sotrovimab in adult patients in the early stages of COVID-19.

a) Adults with COVID-19 who do not require additional oxygen therapy and who are at increased risk of a severe course of COVID-19 if infected with a viral variant against which sotrovimab shows significantly reduced or insufficient efficacy

• For the treatment of adult 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 sotrovimab has significantly reduced or insufficient efficacy, the additional benefit is not proven.
• The COMET-ICE study exclusively investigated patients infected with virus variants against which sufficient neutralising activity was demonstrated.
• Sotrovimab demonstrates significantly reduced efficacy against the Omicron variants circulating exclusively in Germany at the time of the decision (as demonstrated by in vitro neutralisation tests). Due to this significantly reduced efficacy, the effects observed in the COMET-ICE study are not transferable to patients infected with the Omicron variants BA.2, during the benefit assessment, BA.2.12.1, BA.4 or BA.5 at the time of the benefit assessment.
• Consequently, for adults infected with a SARS-CoV-2 variant for which there is evidence, or based on the current pandemic situation, that sotrovimab exhibits significantly reduced or insufficient neutralising activity (currently Omicron variants), no conclusion can be drawn regarding the additional benefit of treating COVID-19 with sotrovimab. For this patient population (patient population a), the additional benefit of sotrovimab 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 virus variant against which Sotrovimab 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 sotrovimab demonstrates sufficient efficacy, there is an hint of considerable additional benefit of sotrovimab compared with the appropriate comparator therapy.
• mortality
  • For the endpoint of overall mortality, there is a statistically significant advantage for sotrovimab compared to the other treatment groups.
• Morbidity – development of severe and/or critical respiratory COVID-19 by day 29
  • For the endpoint ‘development of severe and/or critical respiratory COVID-19’, there is a statistically significant advantage for sotrovimab compared to the other treatment groups.
• Morbidity – Hospitalisation of any duration due to non-respiratory complications of COVID-19 at day 29
  • For the endpoint of hospitalisation of any duration due to non-respiratory complications of COVID-19, there was no statistically significant difference between the treatment groups.
• Morbidity – hospitalisation lasting > 24 hours due to any cause
  • For hospitalisation lasting at least 24 hours due to any cause, there is a statistically significant advantage for sotrovimab compared to the other treatment groups.
• Morbidity – admission to an intensive care unit for any cause at day 29
  • For the endpoint of admission to an intensive care unit for any cause, there was a statistically significant advantage for sotrovimab compared to the other treatment groups.
• Quality of life – SF-12 Hybrid
  • The analyses submitted by the pharmaceutical manufacturer for the SF-12 Hybrid are therefore not usable for the questionnaire in this benefit assessment.
• Side effects – SUEs, severe AEs and discontinuations due to AEs
  • No statistically significant difference was observed between the treatment groups for the endpoints SUEs and severe AEs. No events occurred for the endpoint ‘discontinuation due to AEs’.
• Side effects – infusion-related reactions (ARs and SUEs)
  • For the endpoint ‘infusion-related reactions’ (AEs), there was no statistically significant difference between the treatment groups. No events occurred for the endpoint ‘infusion-related reactions’ (SUEs).
• Overall assessment
  • In the mortality category, a statistically significant advantage was observed between the treatment groups for the endpoint of overall mortality, in favour of sotrovimab.
  • In the morbidity category, statistically significant advantages in favour of sotrovimab compared with the control arm were observed for the endpoints ‘development of severe and/or critical respiratory COVID-19’, ‘hospitalisation for more than 24 hours due to any cause’ and ‘admission to an intensive care unit due to any cause’, statistically significant advantages were observed in favour of sotrovimab compared with the control arm.
  • For the additional endpoint in the morbidity category – hospitalisation of any duration due to non-respiratory complications of COVID-19 – no statistically significant difference was observed between the treatment groups.
  • In the health-related quality of life category, no usable data are available for the SF-12 Hybrid endpoint relating to health-related quality of life.
  • For the endpoints in the ‘side effects’ category, there were neither advantages nor disadvantages for sotrovimab.
  • In summary, positive effects are observed in the categories of mortality and morbidity, with no adverse effects to counterbalance them. In the overall assessment of the results, based on the positive effects observed in the endpoints of overall mortality, ‘development of severe and/or critical respiratory COVID-19’ and ‘admission to an intensive care unit for any cause’ a considerable additional benefit is inferred for adults with COVID-19, when treating infections caused by a viral variant against which sotrovimab has sufficient neutralising activity, compared with standard medical care.
• The certainty of the study results for the present question is therefore reduced overall. Consequently, significant uncertainties remain regarding the transferability to the German healthcare context, which, when considered in the overall assessment of certainty, justify the derivation of a hint of additional benefit.

c) Adolescents aged 12 to < 18 years with a body weight of at least 40 kg who have COVID-19, do not require additional oxygen therapy, and are at increased risk of a severe course of COVID-19

• Additional benefit is not proven for the treatment of adolescent patients with COVID-19 who do not require additional oxygen therapy and who are at increased risk of a severe course of COVID-19.
• 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). As no data are available, it is not possible to make a differentiated assessment of the effect on the different virus variants. For this age group, therefore, the additional benefit of sotrovimab is not proven.

Courtesy translation only, please refer to the German original.