Results From Pivotal Phase 3 PROSPER Trial of XTANDI[TM] (enzalutamide) in Men With Non-Metastatic Castration-Resistant Prostate Cancer Published in New England Journal of Medicine

Tokyo (ots/PRNewswire) -

Results show enzalutamide plus androgen deprivation therapy
significantly reduced the risk of developing metastases or death by
71 percent compared to placebo plus androgen deprivation therapy[i]

FOR EMEA MEDICAL MEDIA ONLY - Astellas Pharma Inc. (TSE: 4503,
President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced
that results from the pivotal Phase 3 PROSPER trial, which evaluated
enzalutamide plus androgen deprivation therapy (ADT) versus placebo
plus ADT in patients with non-metastatic castration-resistant
prostate cancer (CRPC), were published in the New England Journal of
Medicine. The paper, "Enzalutamide in Men with Nonmetastatic,
Castration-Resistant Prostate Cancer", appears in the 28 June print
edition of the Journal.[i]

In the study, enzalutamide plus ADT significantly reduced the risk
of developing metastases or death compared to ADT alone: 23% of
patients in the enzalutamide and ADT arm had metastasis or had died,
vs 49% in the ADT alone arm. The primary endpoint of median
metastasis-free survival (MFS) was 36.6 months for men who received
enzalutamide compared to 14.7 months with ADT alone (n=1401; HR=0.29
[95% CI: 0.24-0.35]; p<0.001).[i]

"I'm pleased with the PROSPER trial results, which confirm that
men with non-metastatic CRPC receiving enzalutamide plus androgen
deprivation therapy (ADT) had an almost two year delay in appearance
of prostate cancer metastasis or death as compared to those taking
ADT," said Maha Hussain, MD, FACP, FASCO, Genevieve Teuton Professor
of Medicine, Robert H. Lurie Comprehensive Cancer Center of
Northwestern University, and lead study investigator.

Based on the results of the PROSPER study, Astellas submitted a
Type II Variation to the European Medicines Agency (EMA) in January
2018 to extend the overall indication for enzalutamide to include
patients with non-metastatic CRPC. Enzalutamide was first approved by
the European Commission in June 2013 for the treatment of adult men
with metastatic CRPC who are asymptomatic or mildly symptomatic after
failure of androgen deprivation therapy in whom chemotherapy is not
yet clinically indicated or whose disease has progressed on or after
docetaxel therapy.[ii] Enzalutamide is not currently licensed in the
European Union for treatment of men with non-metastatic CRPC.

PROSPER Trial Results[i]

PROSPER is a double-blind, placebo-controlled, pivotal phase 3
trial conducted at 300 sites in 32 countries that randomized 1,401
patients with non-metastatic CRPC and a PSA doubling time of 10
months or less, 2:1 to either receive once-daily enzalutamide plus
ADT (n=993) or placebo plus ADT (ADT alone [n=468]), respectively.

Secondary outcomes included a statistically significant delay in
the median time to first use of new antineoplastic therapy (TTA) of
39.6 vs 17.7 months; HR=0.21 [95% CI: 0.17-0.26]; p<0.001 for
patients who received enzalutamide plus ADT compared to those who
received ADT alone. At the first interim analysis of overall
survival, 103 patients (11%) in the enzalutamide group and 62 (13%)
in the placebo group had died. The median overall survival was not
reached in either group. There was no decrease in quality of life
associated with enzalutamide treatment.

The most common adverse events of any grade for patients >=10% and
higher for enzalutamide plus ADT vs ADT alone were: fatigue 33% vs
14%, hot flush 13% vs 8%, nausea 11% vs 9%, hypertension 12% vs 5%,
dizziness 10% vs 4%, fall 11% vs 4% and decreased appetite 10% vs
4%. The adverse events in this trial were consistent with the
established safety profile of enzalutamide.

About Prostate Cancer

Prostate cancer is the second most common cancer in men
worldwide.[iii] In the European Union, the estimated number of new
prostate cancer cases in 2015 was 365,000.[iv] More than 164,000 men
in the United States are estimated to be newly diagnosed with
prostate cancer in 2018.[v]

Castration-resistant prostate cancer (CRPC) refers to the subset
of men whose prostate cancer progresses despite castrate levels of
testosterone (i.e., less than 50 ng/dL).[vi] Non-metastatic CRPC
means there is no clinically detectable evidence of the cancer
spreading to other parts of the body (metastases), and there is a
rising prostate-specific antigen (PSA) level.[vii] Many men with
non-metastatic CRPC and a rapidly rising PSA level go on to develop
metastatic CRPC.[viii],[ix]

About Enzalutamide

Enzalutamide is an oral, once-daily androgen receptor signaling
inhibitor. Enzalutamide directly targets the androgen receptors (AR)
and exerts its effects on all three steps of the AR signaling
pathway:

- Blocks androgen binding: Androgen binding induces a conformational
change that triggers activation of the receptor[x],[xi]
- Prevents nuclear translocation: Translocation of the AR to the
nucleus is an essential step in AR-mediated gene regulation[x],[xi]
- Impairs DNA binding: Binding of the AR to the DNA is essential for
modulation of gene expression[x],[xi]

Important Safety Information for Enzalutamide

For important Safety Information for enzalutamide please see the
full Summary of Product Characteristics at:
https://www.medicines.org.uk/emc/product/3203

About the Pfizer/Astellas Collaboration

In October 2009, Medivation, Inc., which is now part of Pfizer
(NYSE:PFE), and Astellas (TSE: 4503) entered into a global agreement
to jointly develop and commercialize enzalutamide. The companies
jointly commercialize enzalutamide in the United States and Astellas
has responsibility for manufacturing and all additional regulatory
filings globally, as well as commercializing enzalutamide outside the
United States.

About Astellas

Astellas Pharma Inc., based in Tokyo, Japan, is a company
dedicated to improving the health of people around the world through
the provision of innovative and reliable pharmaceutical products. For
more information, please visit our website at
https://www.astellas.com/en.

About Astellas Pharma Europe Ltd.

Astellas Pharma Europe Ltd. operates in 40 countries across
Europe, the Middle East and Africa, and is the regional business 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
organization's focus is to deliver outstanding R&D and marketing to
continue growing in the world pharmaceutical market.

Astellas Forward-Looking Statement

In this press release, statements made with respect to current
plans, estimates, strategies and beliefs and other statements that
are not historical facts are forward-looking statements about the
future performance of Astellas. These statements are based on
management's current assumptions and beliefs in light of the
information currently available to it and involve known and unknown
risks and uncertainties. A number of factors could cause actual
results to differ materially from those discussed in the
forward-looking statements. Such factors include, but are not limited
to: (i) changes in general economic conditions and in laws and
regulations, relating to pharmaceutical markets, (ii) currency
exchange rate fluctuations, (iii) delays in new product launches,
(iv) the inability of Astellas to market existing and new products
effectively, (v) the inability of Astellas to continue to effectively
research and develop products accepted by customers in highly
competitive markets, and (vi) infringements of Astellas' intellectual
property rights by third parties.

Information about pharmaceutical products (including products
currently in development), which is included in this press release is
not intended to constitute an advertisement or medical advice.

i. Hussain, Maha, et al. Enzalutamide in Men with Nonmetastatic
Castration-Resistant Prostate Cancer. N Engl J Med 2018; 378:2465-74

ii. European Medicines Authority. Summary of Product
Characteristics: Xtandi 40 mg soft capsules. Accessed 22-06-18 http:/
/www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Informa
tion/human/002639/WC500144996.pdf

iii. Torre L. et al. Global Cancer Incidence and Mortality Rates
and Trends - an Update. Cancer Epidemiol Biomarkers Prev;
25(1):pp16-27 January 2016

iv. European Commission. Epidemiology of prostate cancer in Europe
(03-17-2017). https://ec.europa.eu/jrc/en/publication/epidemiology-pr
ostate-cancer-europe . Accessed 22-06-2018.

v. American Cancer Society. Key Statistics for Prostate Cancer. ht
tps://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html
. Accessed 06-13-2018.

vi. Kirby M, Hirst C, Crawford ED. Characterising the
castration-resistant prostate cancer population: a systematic review.
Int J Clin Pract 2011;65(11):1180-92.

vii. Luo J, Beer T, Graff J. Treatment of nonmetastatic
castration-resistant prostate cancer. Oncology 2016;30(4):336-44.

viii. Smith MR, Kabbinavar F, Saad F, et al. Natural history of
rising serum prostate-specific antigen in men with castrate
nonmetastatic prostate cancer. J Clin Oncol 2005;23(13):2918-25.

ix. Smith MR et al. Disease and host characteristics as predictors
of time to first bone metastasis and death in men with progressive
castration-resistant nonmetastatic prostate cancer. Cancer 2011;117:
2077-2085

x. Tran C, et al. Development of a second-generation antiandrogen
for treatment of advanced prostate cancer. Science 2009; 324:787-790

xi. Hu R, Denmeade SR and Luo J. Molecular processes leading to
aberrant androgen receptor signaling and castration resistance in
prostate cancer. Expert Rev Endocrinol Metab 2010; 5 (5): 753-764

ots Originaltext: Astellas Pharma Europe Limited
Im Internet recherchierbar: http://www.presseportal.de

Contact:
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