MDV3100 is an investigational therapy in Phase 3 clinical development for the treatment of advanced prostate cancer.

Overview

MDV3100 is the first oral androgen receptor signaling inhibitor (ARSI) in development for the treatment of early-stage and advanced prostate cancer. Based on the mechanism of MDV3100, it could be useful in a broad spectrum of prostate cancer disease states, with the first step to develop it for patients with the most advanced disease and in greatest need.

MDV3100 has a novel mechanism of action that is distinct from other hormonal therapies including bicalutamide and abiraterone. MDV3100 has been shown in preclinical studies to provide a more complete suppression of the androgen receptor pathway than bicalutamide. MDV3100 slows growth and induces cell death in bicalutamide-resistant cancers via three complementary actions – MDV3100 competitively inhibits androgen (testosterone and dihydrotestosterone) binding to the androgen receptor, inhibits movement of the androgen receptor to the nucleus of prostate cancer cells (nuclear translocation), and inhibits binding to DNA. MDV3100 inhibits proliferation and induces cancer cell death and tumor regression in animal models of advanced prostate cancer.  These preclinical data are published in the April 2009 issue of Science. Click here for Science article.

Medivation is evaluating MDV3100 in collaboration with Astellas in an ongoing Phase 3 clinical development program.  Interim results from an open-label, U.S., Phase 1-2 study, published in The Lancet, showed that MDV3100 was associated with anti-tumor activity in patients who had become resistant to bicalutamide or other standard anti-androgen treatments, including both patients who had failed prior chemotherapy and patients who were chemotherapy naïve.  Click here for The Lancet article.

The Phase 3 AFFIRM trial completed enrollment in men with advanced prostate cancer previously treated with docetaxel-based chemotherapy in November 2010. In November 2011, a planned interim analysis showed that MDV3100 significantly improved survival compared to placebo.  The independent drug monitoring committee recommended that the trial be stopped and all placebo patients be offered MDV3100 Click here for press release.  Medivation and Astellas plan to hold a pre-NDA meeting with the U.S. Food and Drug Administration (FDA) in early 2012 and will provide an update on regulatory timelines for MDV3100 subsequent to that meeting.

The Phase 3 PREVAIL trial is currently enrolling men with advanced prostate cancer who have not yet received chemotherapy. The Phase 2 TERRAIN trial, comparing MDV3100 with bicalutamide, is currently enrolling men who have progressed while on LHRH therapy or following surgical castration. In addition, a Phase 2 trial evaluating MDV3100 monotherapy is currently enrolling hormone-naïve patients. Click here for clinical trial information.