Astellas has filed for approval of androgen inhibitor enzalutamide in Europe for use in men with metastatic castration-resistant prostate cancer (mCRPC).
Astellas and co-development partner Medivation are seeking approval of enzalutamide as a second-line treatment for mCRPC in men who have already received docetaxel-based chemotherapy. A marketing application for the oral, once-daily drug has also been submitted in the US.
The submissions are based on data from the late-stage AFFIRM trial, which was stopped early in November 2011 after the drug demonstrated an improvement in overall survival in patients who had failed docetaxel therapy.
At the time the trial was stopped, the experimental androgen receptor signalling inhibitor produced a significant 4.8-month survival advantage compared to placebo, equating to a 37 per cent reduction in the risk of death.
The study also showed that patients who added other treatment options after their disease progressed whilst on enzalutamide were able to stay on treatment longer.
Enzalutamide is considered a first-in-class agent because it acts on androgens in three ways: blocking androgen receptors; inhibiting nuclear translocation of the androgen receptor from the cellular membrane; and preventing the association of the androgen receptor with DNA within the nucleus.
If approved, it will enter a market already seeing the launch of new treatments, notably Johnson & Johnson's Zytiga (abiraterone) which achieved sales of around $200m in the first quarter of 2012.
On paper at least enzalutamide is showing efficacy at least as good as Zytiga, and analysts have predicted that Astellas and Medivation's drug could do as well commercially too. This is in part due to the drugs simpler dosing compared to Zytiga, which is co-administered with prednisone.
Another potential competitor is Dendreon's Proveng, which is starting to gain momentum after a slow start in the prostate cancer market.
Meanwhile, Astellas and Medivation are exploring the use of enzalutamide as earlier-stage therapy.
A phase III trial called PREVAIL is comparing enzalutamide to placebo in patients with asymptomatic CRPC who have not received chemotherapy, while the phase II TERRAIN trial is evaluating the drug in the pre-chemotherapy setting in comparison with bicalutamide.