Quizartinib Medicine 13 December 2018 Extended indication Monotherapy for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML) who are FLT3-ITD mutation-positive. Therapeutic value Possible added value Total cost € 975,000.00 Registration phase Registration application pending Product Active substance Quizartinib Domain Oncology and Hematology Reason of inclusion New medicine (specialité) Main indication Leukemia Extended indication Monotherapy for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML) who are FLT3-ITD mutation-positive. Current proprietary name Already available biosimilars / generics Proprietary name Manufacturer Daiichi Sankyo Portfolio holder Mechanism of action Tyrosine kinase inhibitor Route of administration Oral Therapeutical formulation Film-coated tablet Budgetting framework Intermural (MSZ) Centre of expertise Additional remarks Quizartinib potently inhibits FLT3, a kinase that is mutated in approximately one-third of acute myeloid leukemia (AML) cases. Quizartinib specifically inhibits FLT3-ITD mutations. Patients with FLT3 mutations are less responsive to traditional therapies: For patients with FLT3-ITD mutations in the relapsed or refractory AML indication, the most aggressive form of the disease with the worst prognosis, no targeted therapy is currently available. Registration Registration route Centralised (EMA) Type of trajectory Accelerated assessment Particularity Unknown ATMP Unknown Submission date October 2018 Expected Registration June 2019 Orphan drug Yes Registration phase Registration application pending Reimbursement Medicine sluice Additional remarks Therapeutic value Current treatment options Midostaurin, salvage chemotherapy (e.g. FLAG-IDA, MEC or LoDAC). Therapeutic value Possible added value This assessment does not indicate any potential inclusion in the package. Substantiation Improved OS (primary endpoint) and EFS (secundary endpoint) over salvage chemotherapy. Geen directe vergelijking met midostaurine, maar indicatie is anders dan midostaurine (R/R setting). Duration of treatment Median 4 month / months Frequency of administration 1 times a day Dosage per administration References NCT02039726; Cortes et al. EHA Learning Center. Cortes J. Jun 16, 2018; 218882; Cortes et al. Lancet Oncol. 2018 Jul;19(7):889-903; Cortes et al. Blood. 2018 Aug 9;132(6):598-607 Additional remarks Median drug exposure: 4 cycles, at a 28-day cycle length (until lack of clinical benefit, toxicity, or receipt of transplant). Dose: 53.0 mg quizartinib (equivalent to 60 mg quizartinib dihydrochloride) with 26.5 mg quizartinib (equivalent to 30 mg quizartinib dihydrochloride) lead-in; 26.5 mg quizartinib (equivalent to 30 mg quizartinib dihydrochloride) with 17.7 mg quizartinib (equivalent to 20 mg quizartinib dihydrochloride) lead-in for patients treated with a strong CYP3A inhibitor Expected patient volume per year Patient volume 10 - 20 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References Fabrikant; NKR; Levis. Hematology Am Soc Hematol Educ Program. 2013; 2013: 220–226; kanker.nl. expert opinie Additional remarks 674 diagnoses AML in 2015. Ongeveer 30% heeft een FLT3 mutatie (202). Bij ongeveer de helft van het aantal patiënten komt AML terug (101). De fabrikant verwacht een marktaandeel van 50% (51). In de praktijk zal het waarschijnlijk om beperkte hoeveelheid patiënten gaan die gebridged worden naar allo HCT (met name ook omdat quizartinib pancytopenie geeft moet er gebridged worden naar allo HCT), inschatting expert opinie: 10-20 patiënten. Expected cost per patient per year Cost € 60,000.00 - 70,000.00 This amount gives an indication of the total cost. It is the result of the average expected patient volume times the average cost per patient. both per year. References EPAR midostaurine; medicijnkosten.nl Additional remarks Aangenomen wordt dat quizartinib vergelijkbaar is aan midostaurine. Gemiddeld kregen patiënten 12.763 mg midostaurine tijdens de klinische studies, dit komt neer op 511 tabletten van 25 mg. Totale kosten voor 511 tabletten midostaurine bedragen €64.552,09. Potential total cost per year Total cost € 975,000.00 Total cost for sluice Additional remarks Off label use Off label use Unknown Indications off label use References Additional remarks Indication extension Indication extensions Yes Indication extensions Monotherapy for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3-ITD mutation-positive References Fabrikant; QuANTUM First (ongoing PhIII clinical trial) Additional remarks Expected registration date Q4 2021 Other information Additional remarks