MDV3100 Extends Life by Nearly Five Months in Men with Advanced Prostate Cancer Post Chemotherapy

MDV3100 Extends Life by Nearly Five Months in Men with Advanced Prostate Cancer Post Chemotherapy
New European survey reveals 99% of oncologists and urologists feel there is a need for new treatments in advanced prostate cancer

STAINES, England, Feb 26, 2012 (BUSINESS WIRE) -- Astellas Pharma Europe Ltd. (APEL) announced today that data presented at the European Association of Urology (EAU) congress in Paris, France, have shown that the investigational drug MDV3100 extended life by nearly 5 months, compared to placebo, in men with advanced prostate cancer, previously treated with chemotherapy.(1)

MDV3100, developed by Astellas Pharma Inc. and Medivation Inc., is a novel, oral androgen-receptor signalling inhibitor in clinical development for advanced prostate cancer.(3) Results from the phase III AFFIRM study confirmed that MDV3100 demonstrated a statistically significant improvement (p<0.0001) in overall survival with a median improvement over placebo of 4.8 months [hazard ratio (HR) = 0.631].(1) The study also concluded that MDV3100 was generally well tolerated by patients and met all secondary endpoints.(1)

Results of a new survey, conducted by APEL, of 500 oncologists and urologists across five European countries reveal a call for new treatments in advanced prostate cancer. The research found that 99% of participants believe there is a need for new treatment options to extend the lives of these late stage patients.(2) Findings from the survey also highlight that extended overall survival is deemed to be the most important attribute of a new advanced prostate cancer treatment, (85% of oncologists and 74% of urologists),(2) closely followed by improved tolerability, which was identified as the second most important treatment quality (76% of oncologists and 74% of urologists).(2)

"Extending patients' lives at this late stage of their disease is our primary aim, but it's incredibly important to balance this with the impact treatment may have on patient quality of life," said Professor Axel Heidenreich, Chairman and Director of the Department of Urology, Rheinisch-Westfalische Technische Hochschule (RWTH) University, Aachen, Germany. "These data are encouraging and indicate that as well as extending the time until their disease progresses and providing a significant survival benefit, this is achieved without significant impact on the patient due to side effects."

Secondary endpoints in the study included radiographic progression-free survival (rPFS) and time to prostate-specific antigen (PSA) progression.(1) A median rPFS of 8.3 months was seen in the MDV3100 group compared to 2.9 months for placebo [HR = 0.404].(1) There was a statistically significant (p<0.0001) improvement in time to prostate-specific antigen (PSA) progression (8.3 months versus 3.0 months; p<0.0001; HR=0.249).(1) In addition, PSA declines of 50% or greater were more common in the MDV3100 group than in the placebo group (54.0% versus 1.5%; p<0.0001), as were PSA declines of 90% or greater (24.8% versus 0.9%; p<0.0001).(1)

MDV3100 was generally well tolerated by patients with the majority of adverse events (type and frequency) being comparable to placebo.(1) Common side effects included fatigue, diarrhoea and hot flushes. Adverse events of interest included fatigue (6.3% in the MDV3100 group versus 7.3% in the placebo group), cardiac disorders (0.9% versus 2.0%) including myocardial infarction (0.3% versus 0.5%), seizure (0.6% versus 0.0%) and liver function test abnormalities (0.4% versus 0.8%).(1)

"Around 2.6 million cases of prostate cancer are diagnosed in Europe each year and around 40% of men go on to develop advanced prostate cancer, where the cancer has spread outside the prostate. Although there have been significant advances in the treatment of advanced prostate cancer recently, there are still relatively few options available for these men. Yes, men at this stage of their disease are looking for treatments to keep them alive for longer, but they also want to be able to live their lives as fully as possible. Therefore new advances that may be able to deliver this are very welcome," said Dr Ian Banks, President of the European Men's Health Forum.

Results from the AFFIRM study will be submitted for publication in an appropriate medical journal during 2012.

- Ends -

Dr Ian Banks will be available for interview from today. To arrange an interview, please contact Sarah Mckinnon Clark (details below).

Notes to Editors

About AFFIRM

The phase III AFFIRM trial is a randomised, double-blind, placebo-controlled, multinational trial evaluating MDV3100 (160 mg/day) versus placebo in 1,199 men with advanced prostate cancer who were previously treated with docetaxel-based chemotherapy.(1) Patients were randomised 2:1 to 160 mg of MDV3100 once a day or matching placebo.(1)

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.(1)The AFFIRM study was conducted at sites in the United States, Canada, Europe, Australia, South America and South Africa.(4)

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).(1)

The AFFIRM study was stopped early after the results of the planned interim analysis were deemed positive by the Independent Data Monitoring Committee (IDMC) and all eligible placebo patients were offered MDV3100.(1)

About Advanced Prostate Cancer

Prostate cancer is the most frequently diagnosed cancer in the male population,(5) with some 2.6 million new cases diagnosed each year in Europe alone.(6) Prostate cancer generally affects men over 50 years of age.(7)

Prostate cancer growth is primarily driven by androgen receptor (AR) signalling within the cancer cell.(8) In advanced prostate cancer (APC), the cancer may continue to progress despite prior surgery, radiation therapy and conventional hormone or chemotherapy-based treatments.(9)

When APC progresses despite treatment with androgen-deprivation therapy (ADT), it can be defined as castration-resistant prostate cancer (CRPC). It is thought that AR signalling continues to be an important driver of cancer growth and proliferation in CRPC.(1,8)

Patients with 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.(10)

About MDV3100

MDV3100 is a novel, oral androgen receptor signalling inhibitor in phase III clinical development for advanced prostate cancer.(3) MDV3100 is an investigational drug and is not yet approved for use.

MDV3100 targets the androgen signalling pathway at three distinct points -- it blocks testosterone binding to the androgen receptor, impairs movement of the androgen receptor to the nucleus of prostate cancer cells (nuclear translocation), and inhibits binding to DNA. This has been shown to suppress cancer cell growth and induce cancer cell death (apoptosis).(3)

About the new survey:

This pan-European survey was conducted by Medefield Europe between 6th February 2012 and 14th February 2012. 50 urologists and 50 oncologists were surveyed online from each of the following five European countries: France, Germany, Italy, Spain and the UK. The total survey sample was 500, consisting of 250 oncologists and 250 urologists. This survey was commissioned by Astellas Pharma Europe Ltd. to establish opinions on both the access to treatment for advanced prostate cancer and the unmet need in this area.(2)

About Astellas Pharma Europe Ltd.

Astellas Pharma Europe Ltd., located in the UK, is the European subsidiary of Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals. The organisation is committed to becoming a global company by combining outstanding R&D and marketing capabilities and continuing to grow in the world pharmaceutical market. Astellas Pharma Europe Ltd. is responsible for 21 affiliate offices located across Europe, the Middle East and Africa, an R&D site and three manufacturing plants. The company employs approximately 4,200 staff across these regions. For more information about Astellas Pharma Europe, please visit www.astellas.eu .

About Medivation

Medivation, Inc. is a biopharmaceutical company focused on the rapid development of novel small molecule drugs to treat serious diseases for which there are limited treatment options. Medivation aims to transform the treatment of these diseases and offer hope to critically ill patients and their caregivers. For more information, please visit us at www.medivation.com .

About the Medivation/Astellas Collaboration

In October 2009, Medivation and Astellas entered into a global agreement to jointly develop and commercialise MDV3100. The companies are collaborating on a comprehensive development programme that includes studies to develop MDV3100 across the full spectrum of advanced prostate cancer. Subject to receipt of regulatory approval, the companies will jointly commercialise MDV3100 in the United States and Astellas will have responsibility for commercialising MDV3100 outside the U.S.

References

-- 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

-- Medefield research, February 2012. 250 oncologists and 250 urologists from 5 European countries surveyed

-- 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

-- Clinical Trials.gov, Safety and efficacy Study of MDV3100 in patients with castration-resistant prostate cancer who have been previously treated with docetaxel-based chemotherapy (AFFIRM) NCT00974311. Available at http://clinicaltrials.gov/ct2/show/NCT00974311?term=AFFIRM&rank=1 . Last accessed January 2012

-- 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

-- Montzka K, Heidenreich A. Castration-Resistant Prostate Cancer: Definition, Biology, and Novel Therapeutic Intervention Strategies. AoU 2010

-- McMillan Cancer Support -- Prostate Cancer -- Cancer Information. Available at: http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Prostate/Aboutprostatecancer/Prostatecancer.aspx Last accessed February 2012

-- Lonergan P E, Tindall D J, Androgen receptor signalling in prostate cancer development and progression, J Carcinog 2011;10:20

-- Nieto M, Finn S, Prostate Cancer: re-focusing on Androgen receptor signalling, Int. Journal Cell Biology 2007;39(9):1562-8

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

SOURCE: Astellas


       
        Red Health
        Sarah Mckinnon Clark
        [email protected]
        +44 (0)771 331 3158
        or
        Astellas Pharma Europe Ltd.
        Mindy Dooa
        [email protected]
       

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