Mechanism of Action

ERLEADA is an androgen receptor (AR) inhibitor indicated to treat non-metastatic castration-resistant prostate cancer (CRPC)1

ERLEADA™ inhibits AR signaling at multiple sites of action1:

  • Binds directly to the ligand-binding domain of the AR
  • Inhibits AR nuclear translocation
  • Inhibits DNA binding
  • Impedes AR-mediated transcription

In preclinical and phase 1 studies*:

Dose escalation of ERLEADA™ to 480 mg/day (twice the approved daily dose) did not identify a maximum-tolerated dose in a phase 1 study of 30 patients with progressive, metastatic CRPC2

*Clinical significance is unknown.

ERLEADA™ demonstrated a high tumor-to-plasma ratio in a preclinical mouse xenograft model of prostate cancer3

ERLEADA™ retained antagonistic activity in the setting of AR overexpression in a preclinical binding affinity assay using human prostate cancer cells3

References

1. ERLEADA™ [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.

2. Rathkopf DE, Morris MJ, Fox JJ, et al. Phase I study of ARN-509, a novel antiandrogen, in the treatment of castration-resistant prostate cancer. J Clin Oncol. 2013;31(28):3525-3530.

3. Clegg NJ, Wongvipat J, Joseph JD, et al. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012;72(6):1494-1503.