Entrectinib Medicine 13 December 2018 Extended indication Rozlytrek as monotherapy is indicated for the treatment of adult patients with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors. Therapeutic value Possible added value Total cost € 14,238,000.00 Registration phase Positive CHMP opinion Product Active substance Entrectinib Domain Oncology and Hematology Reason of inclusion New medicine (specialité) Main indication Lung cancer Extended indication Rozlytrek as monotherapy is indicated for the treatment of adult patients with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors. Current proprietary name Already available biosimilars / generics Proprietary name Rozlytrek Manufacturer Roche Portfolio holder Mechanism of action Tyrosine kinase inhibitor Route of administration Oral Therapeutical formulation Tablet Budgetting framework Intermural (MSZ) Centre of expertise Additional remarks Inhibitor of the tyrosine kinases TrkA (coded by the gene NTRK1), TrkB (coded by the gene NTRK2), TrkC (coded by the gene NTRK3), ROS1 (coded by the gene ROS1), and ALK (coded by the gene ALK). Registration Registration route Centralised (EMA) Type of trajectory Normal trajectory Particularity Unknown ATMP Unknown Submission date January 2019 Expected Registration August 2020 Orphan drug No Registration phase Positive CHMP opinion Reimbursement Medicine sluice Additional remarks Positieve CHMP-opinie in juni 2020. Therapeutic value Current treatment options Crizotinib Therapeutic value Possible added value This assessment does not indicate any potential inclusion in the package. Substantiation Er wordt verwacht dat entrectinib een meerwaarde zal hebben ten opzichte van crizotinib door het gunstige veiligheidsprofiel van dit geneesmiddel, het geneesmiddel heeft een lange follow-up tijd voor een brede populatie. Duration of treatment Frequency of administration 1 times a day Dosage per administration 600mg References Fabrikant; clinicaltrials.gov and Doebele et al. 2018 (IASLC); Facchinetti F, Friboulet L. Profile of entrectinib and its potential in the treatment of ROS1-positive NSCLC: evidence to date. Lung Cancer (Auckl). 2019;10:87–94. Published 2019 Sep 9. doi:10.2147/LCTT.S190786 Additional remarks Expected patient volume per year Patient volume 75 - 150 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References NKR; Bubendorf, et al., Virchows Arch. 2016; 469(5): 489–503., Epskamp PALGA/ pulmoscript 2015, expertopinie. Additional remarks Jaarlijks presenteren er ongeveer 7.500 patiënten per jaar met NSCLC stadium IIIb/IV. 1-2% van alle NSCLC patiënten is ROS1 positief (75-150). Het patiëntvolume zal hierdoor kunnen variëren van minimaal 75 tot maximaal 150. Aangezien niet elke patiënt genetisch getest zal worden komt slechts een deel van deze patiënten in aanmerking voor de behandeling. Expected cost per patient per year Cost € 72,000.00 - 180,000.00 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 https://www.reuters.com/article/us-roche-hldg-fda-pricing/roche-cancer-treatment-priced-at-17050-a-month-lower-than-rival-vitrakvi-idUSKCN1V61G8 Additional remarks De lijstprijs voor entrectinib in de Verenigde Staten is gesteld op $17,050 per maand (ongeveer €15.000). Dit is ongeveer de helft van de prijs van concurrent larotrectinib (Bayer). Op jaarbasis bij behandeling van 12 maanden zou dit neerkomen op €180.000. Naar verwachting zal in Europa de prijs wat lager liggen. De fabrikant geeft aan een prijs van €72.000 per patiënt per jaar op basis van 12 maanden behandeling te verwachten. Potential total cost per year Total cost € 14,238,000.00 Total cost for sluice Additional remarks Off label use Off label use No Indications off label use References Fabrikant Additional remarks Indication extension Indication extensions Yes Indication extensions NTRK+ References Fabrikant Additional remarks Other information Additional remarks