Avatrombopag (1) – Doptelet®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer has submitted a meta-analysis of the data from the completed, double-blind, randomised ADAPT-1 and ADAPT-2 trials.
  • The ADAPT-1 and ADAPT-2 studies have an identical study design. In the studies, avatrombopag was compared with placebo.

Adults with severe thrombocytopenia due to chronic liver disease who are scheduled to undergo an invasive procedure

• An additional benefit is not proven.
• In summary, the additional benefit of avatrombopag over a ‘wait-and-see’ approach is not proven.
• mortality
  • Deaths were recorded in the ADAPT-1 and ADAPT-2 studies as part of the adverse event monitoring.
  • The meta-analysis of the studies shows no statistically significant difference between the treatment groups. An additional benefit of avatrombopag for the endpoint of mortality is therefore not proven.
• Morbidity – patients without transfusion
  • The primary endpoint of the ADAPT-1 and ADAPT-2 studies was the proportion of patients who required neither platelet transfusions nor rescue measures due to bleeding from randomisation up to 7 days after a planned procedure.
  • When considering the overall population of the ADAPT-1 and ADAPT-2 studies, a statistically significant difference in favour of avatrombopag is evident.
  • The available patient characteristics and the nature of the planned procedures in the ADAPT-1 and ADAPT-2 studies do not, in themselves, indicate that prophylactic platelet transfusion was indicated for the patients included in the studies.
  • Overall, taking the described factors into account, no additional benefit is inferred from the results for the endpoint ‘patients without transfusion’.
• Morbidity – Bleeding, WHO grade ≥ 2
  • For the endpoint ‘bleeding of WHO grade ≥ 2’, the meta-analysis of the studies shows no statistically significant difference between the study arms.
  • An additional benefit of avatrombopag for the endpoint of bleeding of WHO grade ≥ 2 is therefore not proven.
• quality of life
  • Data on health-related quality of life were not collected in the ADAPT-1 and ADAPT-2 studies.
• Side effects
  • Adverse events occurred in > 50 % of patients in the ADAPT-1 study and in > 40 % of patients in the ADAPT-2 study.
  • There were no statistically significant differences between the study arms for the endpoints of serious adverse events (SAEs) and discontinuation due to AEs.
  • For the endpoint ‘discontinuation due to AEs’, no events occurred in the ADAPT-2 study.
  • For the endpoint of thromboembolic events, there was no statistically significant difference between the treatment arms in the ADAPT-2 study. In the ADAPT-1 study, no events occurred for this endpoint.
• Overall assessment / Conclusion
  • To assess the additional benefit of avatrombopag, the pharmaceutical manufacturer submitted a meta-analysis of the double-blind, randomised Phase III trials ADAPT-1 and ADAPT-2 comparing avatrombopag with placebo, presenting results on mortality, morbidity and side effects.
  • The meta-analysis shows no statistically significant difference in overall survival.
  • For the endpoint of bleeding of WHO grade ≥ 2, the meta-analysis showed no statistically significant difference. An additional benefit of avatrombopag for this endpoint is therefore not proven.
  • No additional benefit is inferred from the results for the endpoint ‘patients without transfusion’.
  • For the endpoints of serious adverse events (SAEs), discontinuation due to AEs and thromboembolic events, no statistically significant effect of avatrombopag was observed in any case. An additional benefit of avatrombopag compared with a ‘wait-and-see’ approach in the ‘side effects’ endpoint category is therefore not proven.
  • In summary, the additional benefit of avatrombopag compared with a ‘wait-and-see’ approach is not proven.

Courtesy translation only, please refer to the German original.