Pfizer and Astellas Announce Top-Line Results from Phase 4 PLATO Trial of XTANDI® (enzalutamide) Capsules in Patients with Metastatic Castration-Resistant Prostate Cancer

NEW YORK & TOKYO–(BUSINESS WIRE)– Pfizer Inc. (NYSE:PFE) and Astellas Pharma Inc. (TSE:4503) today
announced the Phase 4 PLATO study, evaluating the efficacy and safety of
continued treatment with XTANDI^® (enzalutamide),
plus abiraterone acetate and prednisone as compared to treatment with
abiraterone acetate and prednisone alone, did not meet its primary
endpoint of improvement in progression-free survival (PFS) in patients
with chemotherapy-naïve metastatic castration-resistant prostate cancer
(CRPC) whose prostate-specific antigen (PSA) has previously progressed
on XTANDI.

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“While the PLATO trial did not meet its primary endpoint, it is critical
that we continue to focus on addressing the unmet needs of men with
metastatic CRPC, who have a poor prognosis despite treatment advances,”
said Mohammad Hirmand, M.D., interim chief medical officer at
Medivation, Inc., which is now part of Pfizer. “We will continue to
analyze these data to better understand the results with the goal of
further helping these patients.”

“XTANDI continues to remain an important treatment option for men with
metastatic CRPC and their physicians. We are committed to continuing to
explore the clinical potential of XTANDI across the disease continuum,”
said Steven Benner, M.D., senior vice president, therapeutic area head
for oncology development, Astellas.

XTANDI is approved by the U.S. Food and Drug Administration for the
treatment of patients with metastatic castrate-resistant prostate cancer
(CRPC), based on clinical studies showing statistically significant
overall survival benefit versus placebo.

About PLATO

The Phase 4 PLATO trial (NCT01995513) is a global randomized,
double-blind, placebo-controlled, two-period study designed to evaluate
the efficacy and safety of continued treatment with XTANDI plus
abiraterone acetate and prednisone at the time of confirmed PSA
progression, as compared to treatment with abiraterone acetate and
prednisone alone at the time of PSA progression. The study enrolled 509
patients with chemotherapy-naïve metastatic CRPC who received open label
XTANDI during period 1 of the study, until PSA progression was
confirmed. Eligible patients were then randomized to one of the two
treatments and assessed for the primary endpoint of the study, PFS,
defined by either: 1) radiographic progression or 2) unequivocal
clinical progression or 3) death during the study.

Period 1 patients were treated with XTANDI 160mg/day orally and period 2
patients were treated with blinded XTANDI 160 mg/day orally in
combination with abiraterone at a dose of 1,000 mg/day administered
orally and prednisone at a dose of 5 mg administered orally twice daily,
versus placebo plus the same doses of abiraterone acetate and prednisone.

For additional information regarding the PLATO trial, visit clinicaltrials.gov.

About Metastatic Castration-Resistant Prostate Cancer (CRPC)

Metastatic castration-resistant prostate cancer (CRPC) refers to
prostate cancer that has spread to parts of the body other than the
prostate, and continues to spread despite treatment.¹ Up to
40 percent of men diagnosed with prostate cancer who undergo therapy
develop metastatic, or advanced, prostate cancer.² In the
U.S., the five-year relative survival rate for prostate cancer patients
with metastatic disease is 28 percent, compared with 100 percent for
prostate cancer patients with non-metastatic disease.³

About XTANDI^® (enzalutamide) capsules

XTANDI (enzalutamide) is an androgen receptor inhibitor that blocks
multiple steps in the androgen receptor signaling pathway within the
tumor cell. In preclinical studies, enzalutamide has been shown to
competitively inhibit androgen binding to androgen receptors, and
inhibit androgen receptor nuclear translocation and interaction with
DNA. The clinical significance of this mechanism of action (MOA) is
unknown.

XTANDI is approved by the U.S. Food and Drug Administration for the
treatment of patients with metastatic castration-resistant prostate
cancer (mCRPC).

Important Safety Information

Contraindications

XTANDI is not indicated for women. XTANDI can cause fetal harm and
potential loss of pregnancy.

Warnings and Precautions

Seizure occurred in 0.5% of patients receiving XTANDI in
clinical studies. In placebo-controlled studies, 8 of 1671 (0.5%)
patients treated with XTANDI and 1 of 1243 (0.1%) patients treated with
placebo experienced a seizure. In patients who previously received
docetaxel, 7 of 800 (0.9%) patients treated with XTANDI experienced a
seizure and no patients treated with placebo experienced a seizure. In a
placebo-controlled study in chemotherapy-naïve patients, 1 of 871 (0.1%)
treated with XTANDI and 1 of 844 (0.1%) patients treated with placebo
experienced a seizure. In bicalutamide-controlled studies conducted in
chemotherapy-naïve patients, 3 of 380 (0.8%) patients treated with
XTANDI and 1 of 387 (0.3%) patients treated with bicalutamide
experienced a seizure. Permanently discontinue XTANDI in patients who
develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) In post
approval use, there have been reports of PRES in patients receiving
XTANDI. PRES is a neurological disorder which can present with rapidly
evolving symptoms including seizure, headache, lethargy, confusion,
blindness, and other visual and neurological disturbances, with or
without associated hypertension. A diagnosis of PRES requires
confirmation by brain imaging, preferably MRI. Discontinue XTANDI in
patients who develop PRES.

Adverse Reactions

The most common adverse reactions (≥ 10%) that occurred more commonly (≥
2% over placebo) in the XTANDI patients from the two placebo-controlled
clinical trials were asthenia/fatigue, back pain, decreased appetite,
constipation, arthralgia, diarrhea, hot flush, upper respiratory tract
infection, peripheral edema, dyspnea, musculoskeletal pain, weight
decreased, headache, hypertension, and dizziness/vertigo. In the
bicalutamide-controlled study of chemotherapy naïve patients, the most
common adverse reactions (≥ 10%) reported in XTANDI patients were
asthenia/fatigue, back pain, musculoskeletal pain, hot flush,
hypertension, nausea, constipation, upper respiratory tract infection,
diarrhea, and weight loss.

In the study of patients taking XTANDI who previously received
docetaxel, Grade 3 and higher adverse reactions were reported among 47%
of XTANDI patients and 53% of placebo patients. Discontinuations due to
adverse events were reported for 16% of XTANDI patients and 18% of
placebo patients. In the placebo-controlled study of chemotherapy-naïve
patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI
patients and 37% of placebo patients. Discontinuations due to adverse
events were reported for 6% of both study groups. In the
bicalutamide-controlled study of chemotherapy naïve patients, Grade 3-4
adverse reactions were reported in 38.8% of XTANDI patients and 37.6% of
bicalutamide patients. Discontinuations due to adverse events were
reported for 7.6% of XTANDI patients and 6.3% of bicalutamide patients.

Lab Abnormalities: In the two placebo-controlled trials Grade 1-4
neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of
placebo patients (0.5% Grade 3-4). Grade 1-4 thrombocytopenia occurred
in 6% of XTANDI patients (0.3% Grade 3-4) and 5% of placebo patients
(0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of XTANDI
patients (0.2% Grade 3-4) and 16% of placebo patients (0.2% Grade 3-4).
Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients
(0.1% Grade 3-4) and 2% of placebo patients (no Grade 3-4).

Infections: In a study of patients taking XTANDI who previously received
docetaxel, 1% of XTANDI patients compared to 0.3% of placebo patients
died from infections or sepsis. In the placebo-controlled study of
chemotherapy-naïve patients, 1 patient in each treatment group (0.1%)
had an infection resulting in death.

Falls (including fall-related injuries) occurred in 9% of XTANDI
patients and 4% of placebo patients in the two placebo-controlled
trials. Falls were not associated with loss of consciousness or seizure.
Fall-related injuries were more severe in XTANDI patients, and included
non-pathologic fractures, joint injuries, and hematomas.

Hypertension occurred in 11% of XTANDI patients and 4% of placebo
patients in the two placebo-controlled trials. No patients experienced
hypertensive crisis. Medical history of hypertension was balanced
between arms. Hypertension led to study discontinuation in < 1% of all
patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors,
as they can increase the plasma exposure to XTANDI. If co-administration
is necessary, reduce the dose of XTANDI.

Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to
XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19
substrates with a narrow therapeutic index, as XTANDI may decrease the
plasma exposures of these drugs. If XTANDI is co-administered with
warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Please see Full Prescribing Information at https://www.astellas.us/docs/us/12A005-ENZ-WPI.pdf?v=1
for additional safety information.

You are encouraged to report negative side effects of prescription
drugs to the FDA.

Visit www.fda.gov/medwatch
or call 1-800-FDA-1088.

About Pfizer Oncology

Pfizer Oncology is committed to pursuing innovative treatments that have
a meaningful impact on those living with cancer. As a leader in oncology
speeding cures and accessible breakthrough medicines to patients, Pfizer
Oncology is helping to redefine life with cancer. Our strong pipeline of
biologics, small molecules and immunotherapies, one of the most robust
in the industry, is studied with precise focus on identifying and
translating the best scientific breakthroughs into clinical application
for patients across a wide range of cancers. By working collaboratively
with academic institutions, individual researchers, cooperative research
groups, governments and licensing partners, Pfizer Oncology strives to
cure or control cancer with its breakthrough medicines. Because Pfizer
Oncology knows that success in oncology is not measured solely by the
medicines you manufacture, but rather by the meaningful partnerships you
make to have a more positive impact on people’s lives. Learn more about
how Pfizer Oncology is applying innovative approaches to improve the
outlook for people living with cancer at http://www.pfizer.com/research/therapeutic_areas/oncology.

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. We focus on Urology,
Oncology, Immunology, Nephrology and Neuroscience as prioritized
therapeutic areas while advancing new therapeutic areas and discovery
research leveraging new technologies/modalities. We are also creating
new value by combining internal capabilities and external expertise in
the medical/healthcare business. Astellas is on the forefront of
healthcare change to turn innovative science into value for patients.
For more information, please visit our website at www.astellas.com/en.

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 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
commercialize XTANDI in the United States and Astellas has
responsibility for manufacturing and all additional regulatory filings
globally, as well as commercializing XTANDI outside the United States.

Pfizer Disclosure Notice

The information contained in this release is as of December 14, 2016.
Pfizer assumes no obligation to update forward-looking statements
contained in this release as the result of new information or future
events or developments.

This release contains forward-looking information about XTANDI^®
(enzalutamide) that involves substantial risks and uncertainties
that could cause actual results to differ materially from those
expressed or implied by such statements. Risks and uncertainties
include, among other things, uncertainties regarding the commercial
impact of the results of the PLATO study; the uncertainties inherent in
research and development, including the possibility of unfavorable
clinical trial results, including unfavorable new clinical data and
additional analyses of existing clinical data; decisions by regulatory
authorities regarding labeling, safety, and other matters that could
affect the availability or commercial potential of XTANDI; risks related
to the ability to sustain and increase the rate of growth in revenues
for XTANDI despite increasing competitive, reimbursement and economic
challenges; dependence on the efforts and funding by Astellas Pharma
Inc. for the development, manufacturing and commercialization of XTANDI;
and competitive developments.

A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended December
31, 2015 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors” and “Forward-Looking
Information and Factors That May Affect Future Results”, as well as in
its subsequent reports on Form 8-K, all of which are filed with the U.S.
Securities and Exchange Commission and available at www.sec.gov
and www.pfizer.com.

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.

¹ Cancer.net. Treatment of Metastatic Castration-Resistant
Prostate Cancer. http://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer.
Accessed 12-14-2016.

² « Current and emerging treatments in the management of
castration-resistant prostate cancer. » David Shapiro and Basir Tareen.
Expert Rev Anticancer Ther. 2012;12(7):951-964.

³ National Cancer Institute. SEER Cancer Statistics
Factsheets: Prostate Cancer. Available at
seer.cancer.gov/statfacts/html/prost.html. Accessed 12-14-2016.

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