Astellas Announces New Enzalutamide Data Presented During Plenary Presentations at the 2015 European Association of Urology Congress

London (ots/PRNewswire) -

Astellas Pharma Europe Ltd. today announced new data from the
Phase 2 TERRAIN trial of enzalutamide compared to bicalutamide in
metastatic castration-resistant prostate cancer (CRPC), as well as an
updated overall survival analysis from the placebo-controlled Phase 3
PREVAIL trial of enzalutamide in chemotherapy-naive metastatic CRPC.
The data were presented during a plenary session at the 2015 European
Association of Urology (EAU) Congress in Madrid, Spain.

(Logo: http://photos.prnewswire.com/prnh/20140522/689211 )

"The late breaking data presented at this year's EAU Congress
further demonstrate the breadth and depth of the enzalutamide
development programme," said Claire Thom, Pharm.D., Senior Vice
President and Oncology Therapeutic Head, Astellas Pharma Global
Development, Inc. "We are encouraged to see that enzalutamide
continues to generate promising data for men with advanced prostate
cancer and their loved ones."

Highlights of Key Enzalutamide Data

Title: A randomized, double-blind, Phase 2, efficacy and safety
study of enzalutamide vs. bicalutamide in metastatic castrate
resistant prostate cancer: TERRAIN trial[1]

The Phase 2 TERRAIN trial enrolled 375 patients in North America
and Europe. The trial enrolled patients with metastatic prostate
cancer whose disease progressed despite treatment with a luteinising
hormone-releasing hormone (LHRH) analogue therapy or following
surgical castration. The primary endpoint of the trial was
progression-free survival (PFS), defined as time from randomisation
to centrally confirmed radiographic progression, skeletal related
event, initiation of new anti-neoplastic therapy or death, whichever
occurred first. The trial was designed to evaluate enzalutamide at a
dose of 160 mg taken orally once daily versus bicalutamide at a dose
of 50 mg taken once daily, the approved dose in combination with a
LHRH analogue.

"The results of the TERRAIN trial, if confirmed, have the
potential to impact the treatment landscape of metastatic
castration-resistant prostate cancer," said Axel Heidenreich, M.D.,
Ph.D., Professor and Director, Department of Urology, University
hospital, Aachen, Germany. "The study demonstrated an improvement
with enzalutamide over the standard practice of the addition of
bicalutamide to a luteinising hormone-releasing hormone (LHRH)
therapy."

- The study achieved its primary objective of a statistically significant
increase in PFS for enzalutamide compared to bicalutamide. The median PFS in the
enzalutamide arm was 9.9 months longer compared to that in the bicalutamide arm (15.7
vs 5.8 months, respectively) with a Hazard Ratio (HR) of 0.44 (95% confidence
interval, 0.34-0.57; p<0.0001);
- The median time to PSA progression was 13.6 months longer with enzalutamide
(19.4 months) relative to bicalutamide treatment (5.8 months) with a HR of 0.28
(p<0.0001);
- 82% of enzalutamide-treated patients achieved greater than or equal to 50% PSA
reduction from baseline by week 13 vs 21% of bicalutamide-treated patients;
- The median time on enzalutamide treatment was 11.7 months compared to 5.8
months on bicalutamide;
- The safety profile of the enzalutamide-treated patients in TERRAIN is
consistent with the known safety profile of enzalutamide.
- Serious adverse events (AEs) were reported in 31.1% of enzalutamide vs
23.3% bicalutamide patients and Grade 3 or higher cardiac AEs were observed in
5.5% of enzalutamide vs 2.1% of bicalutamide patients. Two seizures were reported
with enzalutamide and 1 with bicalutamide;
- The common (greater than or equal to10%) AEs reported more frequently with
enzalutamide vs bicalutamide were fatigue (27.9% vs 20.1%), back pain (19.1% vs
18.0%), hot flush (14.8% vs 11.1%), hypertension (14.2% vs 7.4%), diarrhea (11.5%
vs 9.0%), weight decreased (10.9% vs 7.9%) and pain in extremities (10.9% vs
5.3%).

Title: Enzalutamide in men with chemotherapy-naïve metastatic
castration-resistant prostate cancer (mCRPC): Final overall survival
analysis of the Phase 3 PREVAIL study[2]

The Phase 3 PREVAIL trial, a randomised, double-blind,
placebo-controlled, multi-national trial, enrolled 1,717 patients at
sites in the United States, Canada, Europe, Australia, Russia, Israel
and Asia, including Japan. The trial enrolled patients with
chemotherapy-naïve metastatic prostate cancer whose disease
progressed on androgen deprivation therapy (i.e., a LHRH therapy or
after bilateral orchiectomy). The co-primary endpoints of the trial
were overall survival and radiographic progression-free survival. The
trial was designed to evaluate enzalutamide at a dose of 160 mg taken
orally once daily versus placebo.

"The most interesting observations around these data are that
enzalutamide achieved significant overall survival despite many
patients receiving additional treatment, and that the diagnosis of
when a patient's disease becomes metastatic, which drives the timing
of therapy initiation, is important," said Bertrand Tombal, M.D.,
Ph.D., Professor and Chairman, Department of Urology, Universite
catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels.
"The standard approach, as done in the placebo arm of PREVAIL, is to
wait usually for some symptoms or rapid radiological progression
before initiating chemotherapy. However, this study demonstrated that
starting patients on enzalutamide at the point when their
castration-resistant prostate cancer becomes metastatic has the
potential to prolong survival."

- An updated overall survival analysis was conducted at 784 deaths and found
a statistically significant overall survival benefit with a 23% reduction in risk of
death (OS: HR 0.77; 95% CI 0.67-0.88; P=0.0002) and a 4-month improvement in median
survival with enzalutamide (35.3 months [95% CI 32.2-not yet reached]) over placebo
(31.3 months [95% CI 28.8-34.2]). As of the June 2014 cut-off date with a median
follow-up duration of 31 months:
- 52% of enzalutamide and 81% of placebo patients received greater than or
equal to1 subsequent life-extending prostate cancer therapy.

About XTANDI(TM) (enzalutamide)

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

- Blocks androgen binding[3]
- Androgen binding induces a conformational change that triggers activation
of the receptor[4]
- Prevents nuclear translocation[3]
- Transit of the AR to the nucleus is an essential step in AR-mediated gene
regulation[4]
- Impairs DNA binding[3]
- Binding of the AR to the DNA is essential for modulation of gene
expression[4]

Enzalutamide was first approved by the European Commission in June
2013 for the treatment of adult men with mCRPC whose disease has
progressed on or after docetaxel therapy.[5] Enzalutamide is now
approved in Europe for the treatment of adult men with metastatic
castration-resistant prostate cancer who are asymptomatic or mildly
symptomatic after failure of androgen deprivation therapy in whom
chemotherapy is not yet clinically indicated.[5]

Important Safety Information for XTANDI(TM) (enzalutamide)

For important Safety Information for enzalutamide please see the
full Summary of Product Characteristics at: http://www.medicines.org.
uk/emc/medicine/27912/SPC/Xtandi+40mg+soft+capsules.

About Astellas

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
organisation's focus is to deliver outstanding R&D and marketing to
continue growing in the world pharmaceutical market. Astellas'
presence in Europe also includes an R&D site and three manufacturing
plants. The company employs approximately 4,350 staff across these
countries. For more information about Astellas Pharma Europe Ltd.,
please visit http://www.astellas.eu.

About the Medivation/Astellas Collaboration

In October 2009, Medivation and Astellas entered into a global
agreement to jointly develop and commercialise enzalutamide. The
companies are collaborating on a comprehensive development program
that includes studies to develop enzalutamide across the full
spectrum of advanced prostate cancer as well as advanced breast
cancer. The companies jointly commercialise XTANDI in the United
States and Astellas has responsibility for manufacturing and all
additional regulatory filings globally, as well as commercialising
XTANDI outside the United States.

References

1. A randomized, double-blind, phase 2, efficacy and safety study
of enzalutamide vs. bicalutamide in metastatic castrate resistant
prostate cancer: TERRAIN trial. Abstract presented at EAU 2015

2. Enzalutamide in men with chemotherapy-naïve metastatic
castration-resistant prostate cancer (mCRPC): Final overall survival
analysis of the phase 3 PREVAIL study. Abstract presented at EAU 2015

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

4. 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

5. European Medicines Agency. XTANDI (enzalutamide). Summary of
Product Characteristics, 2015

Photo:
http://photos.prnewswire.com/prnh/20140522/689211

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

Contact:
Astellas Contact: AJ Kenneally, Corporate Communications,
+44-(0)7775-113515, AJ.Kenneally@astellas.com