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Positive CHMP Opinion For Xtandi™ (Enzalutamide) In Advanced Prostate Cancer

Enzalutamide recommended for approval in the (EU) for the treatment of adult men with metastatic castration-resistant whose disease has progressed on or after docetaxel therapy 1

Astellas Pharma Europe Ltd., the European Headquarters of Tokyo-based Astellas Pharma (TSE:4503), and Medivation, (Nasdaq: MDVN) have received a positive opinion from the ’s (EMA) Committee for Medicinal Products for Human Use (CHMP), recommending European Commission (EC) approval for Xtandi (enzalutamide) capsules for the treatment of adult men with metastatic castration-resistant prostate cancer whose disease has progressed on or after docetaxel therapy.1

Enzalutamide is a novel, oral, once-daily signalling inhibitor2. Enzalutamide inhibits signalling in three distinct ways: it inhibits 1) testosterone binding to ; 2) nuclear translocation of ; and 3) DNA binding and activation by .

The positive CHMP opinion is based on results from the phase III AFFIRM study which confirmed that enzalutamide demonstrated a statistically significant improvement (p<0.0001) in overall survival compared to placebo, with a median survival of 18.4 months in the enzalutamide group versus 13.6 months in the placebo group, an advantage of 4.8 months [hazard ratio (HR) = 0.631]. The study also concluded that enzalutamide was generally well tolerated by patients and met all secondary endpoints.3

The CHMP’s positive recommendation will be reviewed by the European Commission (EC), which has authority to approve medicines for the European Union. Astellas anticipates a final decision from the EC shortly, as this usually occurs approximately 60 days after a CHMP recommendation.

Professor Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Head of the Drug Development Unit at The Royal Marsden NHS Foundation Trust, comments: “This is an important development in prostate cancer therapeutics that will provide a critically important new treatment option for patients with advanced prostate cancer. Enzalutamide has a major impact on quality of life and survival from this common disease, and will hopefully become a key component of prostate cancer treatment initially in late stage disease following chemotherapy.”

About Prostate Cancer

Prostate cancer is the most frequently diagnosed cancer among European men and it is becoming more common.4,5 Advanced prostate cancer is defined as cancer that has spread outside of the prostate to other areas of the body (metastasised).6 A high number of men with advanced prostate cancer eventually develop a resistance to first-line treatment, which is called castration-resistant prostate cancer (CRPC).7

Patients with metastatic CRPC currently have few treatment options. There is an unmet need in this area for new compounds that target the cancer differently and which may provide alternative therapeutic options for patients at this late stage of their disease.8

About Enzalutamide

Enzalutamide is a novel, oral, once-daily androgen receptor signalling inhibitor.2,3

Enzalutamide inhibits androgen receptor signalling in three distinct ways: it inhibits 1) testosterone binding to androgen receptors; 2) nuclear translocation of androgen receptors; and 3) DNA binding and activation by androgen receptors. 2,3

Xtandi™ (enzalutamide) was approved by the U.S. Food and Drug Administration on August 31, 2012 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel (chemotherapy).


The phase III AFFIRM trial is a randomised, double-blind, placebo-controlled, multinational trial evaluating enzalutamide (160 mg/day) versus placebo in 1,199 men with progressive metastatic castration-resistant prostate cancer who were previously treated with docetaxel-based chemotherapy. Enrolment was completed in November 2010 and the interim analysis was triggered at 520 events. The median age of study participants was 69 years at baseline.3

The AFFIRM study was conducted at sites in the United States, Canada, Europe, Australia, South America and South Africa.3

The primary endpoint of the AFFIRM trial was overall survival. Key secondary endpoints included time to prostate-specific antigen (PSA) progression, radiographic progression free survival (rPFS) and time to first skeletal-related event (SRE).3

In the phase III AFFIRM trial, enzalutamide was generally well tolerated.3 The most common adverse reactions were hot flushes and headache.9 Seizure was reported in 0.8% of enzalutamide-treated patients.9 Serious adverse events, adverse events causing patients to stop treatment, and adverse events causing death were all lower in the enzalutamide group than in the placebo group.3


1. Committee for Medicinal Products for Human Use (CHMP). Summary of opinion (initial authorisation). Xtandi (last accessed April 2013)

2. Scher H I, et al. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study. The Lancet 2010;375(9724):1437-46

3. Scher H I, et al. MDV3100, an Androgen Receptor Signaling Inhibitor (ARSI), Improves Overall Survival in Patients With Prostate Cancer Post Docetaxel; Results From the Phase 3 Affirm Study. Presented at ASCO-GU, 02 February 2012

4.Globocan 2008. WHO Europe Region (EURO); Prostate cancer incidence, mortality and prevalence worldwide in 2008European Union (EU-27): estimated incidence, mortality and 5-year prevalence: men. (last accessed February 2013)

5.Beltran H. et al, Collaborative Review – Prostate Cancer New Therapies for Castration-Resistant Prostate Cancer: Efficacy and Safety, European Urology 2011; 60(2):279-290

6. Moul JW. The evolving definition of advanced prostate cancer. Rev Urol. 2004; 6(Suppl 8): S10–S17.

7. Macmillan Cancer Support, Hormonal therapy for advanced prostate cancer. Available here (last accessed March 2013)

8. Yap T A, et al. The changing therapeutic landscape of castration-resistant prostate cancer, Nat. Rev. Clin. Oncol 2011;8(10):597-610

9. SMPC. Astellas Pharma Europe Ltd. Data on file