US FDA grants orphan drug status to selumetinib
AstraZeneca announced that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation for the investigational MEK 1/2 inhibitor, selumetinib (AZD6244, ARRY-142886) for adjuvant treatment of patients with stage III or IV differentiated thyroid cancer (DTC). AstraZeneca acquired exclusive worldwide rights to selumetinib from Array BioPharma Inc. in 2003.
Sean Bohen executive vice president, global medicines development and chief medical officer, at AstraZeneca, said: “Uptake of RAI is crucial for patients with thyroid cancer where no other therapies have proven beneficial. Selumetinib could significantly enhance currently available treatment options for these patients.”
Selumetinib inhibits the MEK pathway in cancer cells to prevent tumour growth. It is being tested in the phase III ASTRA trial in patients with DTC who are at high risk of recurrence. In a phase II study of selumetinib in patients with advanced thyroid cancer, clinically meaningful increases in iodine uptake and retention were seen in patients with thyroid cancer that was refractory to RAI.
In addition to DTC, selumetinib is being tested in SELECT-1, a phase III trial of patients with KRAS-mutant advanced non-small cell lung cancer (NSCLC) and in a phase II registration trial of paediatric and adolescent patients with neurofibromatosis Type 1 in collaboration with the US National Cancer Institute.
Selumetinib is an oral, potent, selective inhibitor of MEK, part of the mitogen-activated protein kinase (MAPK) pathway which is frequently activated in cancer, including those with the KRAS mutation, which is present in 20% of human cancers and 20-30% of non-small cell lung cancer tumours.
MAPK activation also inhibits expression of thyroid hormone biosynthesis genes, including the sodium/iodine symporter (NIS) which facilitates iodine uptake into cells. Pre-clinical studies have suggested that following MAPK inhibition, iodine uptake by thyroid tumour cells is regained.
ASTRA is a phase III randomised, double blind study which is comparing the complete remission rate following a 5-week course of selumetinib or placebo and single dose adjuvant radioactive iodine therapy in patients with differentiated thyroid cancer.