Midostaurin (2) – Rydapt®

• Clinical trials
  • RATIFY is a completed, randomised, double-blind Phase III trial.
  • In the RATIFY trial, midostaurin was compared with placebo, in each case in combination with daunorubicin and cytarabine as induction therapy, in combination with high-dose cytarabine as consolidation therapy, and as monotherapy for maintenance therapy.
  • AMLSG 16-10 is a single-arm trial involving 440 patients aged between 18 and 70 years with an FLT3-ITD mutation and a diagnosis of AML, AML-associated myeloid precursor neoplasia or acute leukaemia of uncertain lineage.

Adults with newly diagnosed acute myeloid leukaemia (AML) who have an FLT3 mutation

• The additional benefit is not proven.
• Consequently, no additional benefit of midostaurin has been demonstrated in adults with newly diagnosed acute myeloid leukaemia (AML) who harbour an FLT3 mutation, when used in combination with standard chemotherapy comprising daunorubicin and cytarabine for induction and high-dosechemotherapy with cytarabine for consolidation, and subsequently as monotherapy for maintenance treatment in patients in complete remission, compared with the appropriate comparator therapy specified for the resolution.
• Overall assessment
  • For the present reassessment of midostaurin following the exceeding of the €30 million threshold for orphan drugs, the pharmaceutical manufacturer presents the results from the RATIFY, A2220 and AMLSG 16-10 studies as evidence of additional benefit in the treatment of newly diagnosed acute myeloid leukaemia (AML) with an FLT3 mutation, the pharmaceutical company has submitted the results from the RATIFY, A2220 and AMLSG 16-10 studies.
  • The A2220 and AMLSG 16-10 studies, as well as the indirect comparisons presented in the AMLSG 16-10 study are not suitable for the benefit assessment due to the failure to implement the appropriate comparator therapy or the use of midostaurin in a manner not compliant with the marketing authorisation.
  • With regard to maintenance therapy, the appropriate comparator therapy specified in this decision was not implemented in the RATIFY study. The data from the RATIFY study therefore do not permit an assessment of the additional benefit compared with the appropriate comparator therapy specified in this decision.
  • No suitable data are available for a comparison with the appropriate comparator therapy specified for this resolution.

Courtesy translation only, please refer to the German original.