Enzalutamide

• 4 - {3 - [4- cyano-3- (trifluoromethyl ) phenyl] -5,5- dimethyl-4- oxo-2- sulfanylidenimidazolidin -1 -yl} -2-fluoro -N- methylbenzamide (IUPAC)
• MDV3100

Not yet assigned

Not yet assigned

Inhibition of androgen receptor signaling pathway

200-202 ° C

Soluble in DMSO and methanol

Template: Infobox chemical / molecular formula search available

Enzalutamid is an inhibitor of androgen receptor signaling pathway. Enzalutamid was developed by Medivation. In 2009, Astellas Pharma and Medivation entered into an agreement on a common development and global distribution of Enzalutamid.

Mechanism of Action

Enzalutamid inhibits the signaling of the androgen receptor in three places. First, it binds to the androgen receptor, and thus block the binding of the natural ligands, such as testosterone or dihydrotestosterone. Second, the translocation of the androgen receptor is inhibited in the cell nucleus by Enzalutamid. And third, it reduces the binding to the DNA and the recruitment of cofactors for transcription. By this mechanism is the three-fold overexpression of the genes that are regulated by the androgen receptor is inhibited ( inhibited ). Enzalutamid thus differs from previously available anti-androgenic substances.

Phase III trials

In September 2009, the Phase III AFFIRM trial in which 1,199 patients were treated castration-resistant prostate cancer with metastatic after prior chemotherapy with Enzalutamid or placebo started. The primary endpoint of the study was the prolongation of overall survival of Enzalutamid compared to placebo. 800 patients received Enzalutamid, 399 patients were in the placebo group. In September 2011 the study after a planned interim analysis on the recommendation of the independent Data Monitoring Comittees ended prematurely because patients with a Enzalutamid treatment, a 4.8 months longer overall survival than patients in the placebo group ( 18.4 vs. 13, 6 months, hazard ratio (HR ) = 0.63, p < 0.001). Patients from the placebo group was offered after the unblinding of the study Enzalutamid as therapy. Also in the secondary endpoints Enzalutamid was superior to placebo. Progression-free survival as determined by radiographic imaging was 5.4 months in the Enzalutamid group compared to placebo ( 8.3 months vs. 2.9 months; . P < 0.001) as well as in the PSA detection at 5.3 months extended; (p < 0.001. 8.3 months vs 3.0 months). 54 % of patients with a Enzalutamid therapy had a reduction in PSA compared to baseline of ≥ 50 % (p < 0.001). 43% of Enzalutamid patients reported an improved quality of life compared with 18 % of placebo patients ( p < 0.001). ( 7)

Approval Status

In August 2012, the U.S. Food and Drug Administration ( FDA) granted approval for Enzalutamid for treatment of metastatic castration-resistant prostate cancer after docetaxel therapy. In June 2013 Enzalutamid was approved by the European Medicines Agency ( EMA) in Europe for the treatment of patients with metastatic castration-resistant prostate cancer whose disease progresses during or after docetaxel therapy.

Finished medicinal product

• Xtandi (EU, USA)