Lusutrombopag (1) – Mulpleo®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer has submitted a meta-analysis of data from the completed, double-blind, randomised trials M0626, L-PLUS 1 and L-PLUS 2, which compared lusutrombopag with placebo.
  • The M0626 trial was conducted between August 2012 and April 2013 at 63 centres in Japan.
  • The L-PLUS 1 trial was conducted between October 2013 and May 2014 at 81 centres in Japan.
  • The multinational L-PLUS 2 study was conducted from July 2015 to April 2017 at 138 study centres in the Americas, Europe, Australia and Asia.

Adults with severe thrombocytopenia due to chronic liver disease who require invasive procedures

• An additional benefit is not proven.
• In summary, additional benefit from Lusutrombopag compared with a ‘wait-and-see’ approach is not proven.
• mortality
  • For the endpoint of all-cause mortality, the L-PLUS 2 study showed no statistically significant difference between the treatment groups.
  • No deaths occurred in the L-PLUS 1 and M0626 studies.
• Morbidity – patients without transfusions
  • The primary endpoint of the L-PLUS 2 study was the proportion of patients who required neither platelet transfusions prior to the invasive procedure nor emergency measures due to bleeding after randomisation and up to 7 days following the procedure.
  • The primary endpoint of the L-PLUS 1 and M0626 studies was the proportion of patients who did not receive platelet transfusions prior to the invasive procedure.
  • When analysing the results for the endpoint ‘patients without transfusion’, a statistically significant difference in favour of lusutrombopag is evident in the L-PLUS 2, L-PLUS 1 and M0626 studies.
  • Overall, taking into account the considerations described, no additional benefit is inferred from the results for the endpoint ‘patients without transfusion’.
• Morbidity – Bleeding, WHO grade ≥ 2
  • For the endpoint ‘bleeding events of WHO grade ≥ 2’, no statistically significant difference was observed between the treatment arms in the L-PLUS 2 study.
  • In the L-PLUS 1 and M0626 studies, one person in each study experienced serious bleeding; however, bleeding events were not recorded according to the WHO severity classification.
  • An additional benefit of lusutrombopag for the endpoint of bleeding of WHO grade ≥ 2 is therefore not proven.
• Health-related quality of life
  • Data on health-related quality of life were not collected in the L-PLUS 2, L-PLUS 1 and M0626 studies.
• Side effects
  • Adverse events occurred in > 40% of patients in the treatment arms of the L-PLUS 2 study, in > 90% of patients in the L-PLUS 1 study, and in 100% of patients in the M0626 study.
  • With regard to the endpoint of serious adverse events (SAEs), the meta-analysis of the three studies shows no significant difference between the study arms.
  • For the endpoint ‘withdrawal due to AEs’, there was no significant difference between the study arms in the L-PLUS 2 study.
  • In the L-PLUS 1 and M0626 studies, no events occurred for this endpoint.
  • For the endpoint of thromboembolic events, the meta-analysis of the three studies shows no statistically significant difference.
• Overall assessment / Conclusion
  • To assess the additional benefit of lusutrombopag, the pharmaceutical manufacturer submitted a meta-analysis of the double-blind, randomised trials L-PLUS 2, L-PLUS 1 and M0626, comparing lusutrombopag with placebo and providing results on mortality, morbidity and side effects.
  • No statistically significant difference was observed for overall survival.
  • In the morbidity endpoint category, results are available for the endpoints ‘patients without transfusion’ and ‘bleeding of WHO grade ≥ 2’.
  • No statistically significant difference was observed for the endpoint ‘bleeding of WHO grade ≥ 2’. An additional benefit of lusutrombopag for this endpoint is therefore not proven.
  • No additional benefit is inferred from the results for the endpoint ‘patients without transfusion’.
  • For the endpoints serious adverse events (SAEs), discontinuation due to AEs and thromboembolic events, no statistically significant difference was observed between lusutrombopag and placebo in each case. An additional benefit of lusutrombopag compared with a ‘wait-and-see’ approach in the ‘side effects’ endpoint category is therefore not proven.
  • In summary, the additional benefit of lusutrombopag over a ‘wait-and-see’ approach is not proven.

Courtesy translation only, please refer to the German original.