Midostaurin is a new orally administered multi-target receptor tyrosine kinase inhibitor for the treatment of Acute Myeloid Leukaemia (AML). It was designated as an orphan medicinal product in 2004. Marketing authorisation was granted for midostaurin on 18th September 2017. The assessment of clinical effectiveness was based on three studies: The RATIFY trial, the IIT-trial and the UK NCRI AML17 trial.

RATIFY was a randomised phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3-mutated AML. In total, 717 patients aged 18–60 years were included in the full analysis set of the trial. This was the most important study to this assessment and is the pivotal trial of midostaurin in this indication.

Midostaurin in combination with standard induction and consolidation chemotherapy improved overall survival (OS) in patients aged 18–60 years who were fit for chemotherapy. In the RATIFY trial, the risk of death was reduced by 23% during the follow-up for the midostaurin versus placebo groups. The proportion of patients alive in the midostaurin and placebo treatment arms were: 1 year – 76% versus 68%; 5 years – 51% versus 43%. However, because of a plateau effect in the OS curves, the absolute OS gain was difficult to determine reliably. Overall, key secondary outcomes support the conclusions based on the primary outcome (OS). No data on the health-related quality of life or disease-specific quality of life were available. Based on the indirect comparison of midostaurin in combination with standard induction ("7+3 regimen") and consolidation chemotherapy versus high-dose (90mg/m2) daunorubicin induction ("10+3 regimen") and consolidation chemotherapy, there was no evidence that midostaurin treatment was more beneficial than high-dose daunorubicin used during induction, or vice versa. However, serious limitations apply to this indirect comparison.