Tagrix contains osimertinib, an irreversible EGFR tyrosine kinase inhibitor.
Pharmacology
Osimertinib inhibits mutant EGFR forms including T790M, L858R and exon 19 deletion mutations.
Pharmacokinetics
Beacon’s product information reports:
- Median time to maximum plasma concentration: approximately 6 hours.
- Population-estimated mean half-life: approximately 48 hours.
- Approximately three-fold accumulation with once-daily dosing.
- Steady-state exposure after approximately 15 days of dosing.
- Primary elimination through feces, with a smaller proportion through urine.
Metabolism
Osimertinib undergoes oxidation, predominantly involving CYP3A, and dealkylation. Two pharmacologically active metabolites, AZ7550 and AZ5104, have been identified.
Biomarker testing
EGFR testing is central to treatment selection. FDA companion-diagnostic documentation identifies exon 19 deletions, L858R and T790M among relevant biomarkers for osimertinib-associated treatment.
Clinical development
Osimertinib was originally developed by AstraZeneca and became associated with the reference product TAGRISSO. The original European application focused on T790M-positive locally advanced or metastatic NSCLC after progression on or following EGFR TKI treatment.