Kadmon Holdings, Inc. announced this morning that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to tesevatinib for the treatment of non-small cell lung cancer (NSCLC) with epithelial growth factor receptor (EGFR)-activating mutations.
The drug was previously granted the same designation in March 2016 for the treatment of autosomal recessive polycystic kidney disease (ARPKD).
EGFR, a cell surface receptor, has a gene that is amplified in more than half of all gliomas. Studies have shown other EGFR inhibitors to have poor brain penetration, which limits their abilities to reach and successfully treat brain tumors. Different from other EGFR inhibitors, tesevatinib has been observed to be highly blood-brain barrier penetrant, reaching equivalent concentrations in the brain and the blood.
The company is currently conducting an ongoing Phase 2 clinical trial evaluating the oral tyrosine kinase inhibitor in NSCLC with EGFR-activating mutations
that has metastasized to the brain or meninges surrounding the central nervous system. The drug is also being investigated in a separate study assessing it in patients with recurrent glioblastoma
. In August 2016, Rare Disease Report
covered the recruitment of subjects for the latter.
“We are encouraged by tesevatinib’s potential ability to cross the blood-brain barrier in humans, which may lead to meaningful clinical activity against brain tumors,” said Harlan W. Waksal, MD, President and Chief Executive Officer at Kadmon Holdings in a press release
a year ago.
In the study evaluating tesevatinib for the treatment of NSCLC with EGFR-activating mutations, 3 cohorts will be assessed: Cohort A will administer a 300-mg dose of tesevatinib once daily to subjects with NSCLC who have progressed with brain metastases (BM), Cohort B will administer a 300-mg dose of tesevatinib once daily to subjects with NSCLC who have progressed with Leptomeningeal Metastases (LM), and Cohort C will administer a 300-mg dose of tesevatinib once daily to subjects with NSCLC who have progressed with BM at initial presentation.
Primary outcome measures for all 3 cohorts include the evaluation of clinical activity of tesavatinib. Secondary outcome measures include quality of life in subjects receiving the drug, as well as median progression-free survival and median overall survival, among others.
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