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Endoxifen Add-On Restores Tamoxifen Levels in Poor Metabolizers, Phase 1/2 Trial Finds

The strategy addresses genetic shortfalls in CYP2D6 activity that leave many patients below therapeutic targets.

The shadow of a woman is seen on a pedestrian crossing painted in pink for Breast Cancer Awareness Month, in Noyelles-sur-Escaut, France, October 16, 2021. REUTERS/Pascal Rossignol

Overview

  • In the randomized TAMENDOX phase 1/2 study of 235 early-stage hormone receptor–positive patients across 38 German clinics, supplementation was guided by genotype or measured drug levels over six weeks.
  • Patients receiving the add-on achieved blood concentrations comparable to those of normal metabolizers on standard therapy.
  • Side effects were mild and occurred at similar rates to monotherapy, indicating good short-term tolerability.
  • Premenopausal patients could benefit in particular because alternatives such as aromatase inhibitors are limited for them.
  • A U.S. mid-stage trial in premenopausal women is ongoing, and study sponsor Atossa Therapeutics says it plans an FDA filing in 2026 as IKP advances European approval planning.