Pfizer and Astellas Announce Positive Top-Line Results from Phase 3 PROSPER Trial of XTANDI (enzalutamide) in Patients with Non-Metastatic Castration-Resistant Prostate Cancer

NEW YORK & TOKYO–(BUSINESS WIRE)– Pfizer Inc. (NYSE:PFE) and Astellas Pharma Inc. (TSE: 4503, President
and CEO: Yoshihiko Hatanaka, “Astellas”) announced today that the Phase
3 PROSPER trial evaluating XTANDI^® (enzalutamide) plus
androgen deprivation therapy (ADT) versus ADT alone in patients with
non-metastatic (M0) Castration-Resistant Prostate Cancer (CRPC) met its
primary endpoint of improved metastasis-free survival (MFS). The
preliminary safety analysis of the PROSPER trial appears consistent with
the safety profile of XTANDI in previous clinical trials.

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“Many prostate cancer patients who initiate androgen deprivation therapy
will experience disease progression illustrated by a rising PSA level,
and currently, there are no FDA-approved treatment options for patients
with non-metastatic CRPC until they develop confirmed radiographic
metastatic disease,” said Neal Shore, M.D., director, CPI, Carolina
Urologic Research Center.

Based on the results of PROSPER, the companies intend to discuss the
data with global health authorities to potentially support expanding the
label for XTANDI to cover all patients with CRPC.

“We are delighted with the significant results seen in the PROSPER
study, showing that XTANDI plus ADT delayed clinically detectable
metastases compared to ADT alone in patients with non-metastatic CRPC
whose only sign of underlying disease was a rapidly rising
prostate-specific antigen (PSA) level. We look forward to discussing the
data with regulatory authorities,” said Mace Rothenberg, M.D., chief
development officer, Oncology, Pfizer Global Product Development.
“XTANDI is already established as a standard of care for men with
metastatic CRPC based on the results of prior studies, such as AFFIRM
and PREVAIL, which demonstrated that XTANDI delayed disease progression
and improved overall survival in men with clinically detectable
metastatic disease.”

“We want to thank the patients, family members and clinicians who
participated in the PROSPER trial and helped advance the scientific
understanding of the potential role for XTANDI in this prevalent
disease,” said Steven Benner, M.D., senior vice president and global
therapeutic area head, oncology development, Astellas. “We look forward
to further analyzing the detailed efficacy and safety results from
PROSPER, and submitting them for presentation at an upcoming major
medical meeting.”

As part of Pfizer and Astellas’ ongoing commitment to the clinical
development of enzalutamide in areas of greatest unmet need, the
companies initiated the PROSPER trial to evaluate the potential benefits
of XTANDI in men with non-metastatic CRPC, an earlier stage of prostate
cancer where there are currently no FDA-approved treatment options. On
June 9, 2017, the companies announced an amendment to the PROSPER
protocol, which accelerated the clinical trial completion date by two
years.

XTANDI is currently approved for the treatment of metastatic CRPC based
on clinical data from previous studies that showed a statistically
significant overall survival benefit for XTANDI versus placebo in the
metastatic CRPC setting. XTANDI has been prescribed to more than 185,000
patients globally since its first approval in 2012.

About PROSPER

The Phase 3 randomized, double-blind, placebo-controlled, multi-national
trial enrolled approximately 1,400 patients with non-metastatic
castration-resistant prostate cancer (CRPC) at sites in the United
States, Canada, Europe, South America and the Asia Pacific region.
PROSPER enrolled patients with prostate cancer that had progressed,
based on a rising prostate-specific antigen (PSA) level despite androgen
deprivation therapy (ADT), but who had no symptoms with no prior or
present evidence of metastatic disease. The primary objective of the
trial was metastasis-free survival (MFS). MFS is a measure of the amount
of time that passes until a cancer can be radiographically detected as
having metastasized, or spread, to other parts of the body. The trial
evaluated enzalutamide at a dose of 160 mg taken orally once daily plus
ADT, versus placebo plus ADT. For more information on the PROSPER trial
go to www.clinicaltrials.gov.

XTANDI has not yet been evaluated by the FDA for the treatment of
patients with non-metastatic CRPC.

About Non-Metastatic Castration-Resistant Prostate Cancer

According to the American Cancer Society, more than 161,000 men are
estimated to be diagnosed with prostate cancer in 2017.^[i]
Castration-resistant prostate cancer (CRPC) refers to the subset of men
whose prostate cancer progresses despite androgen deprivation therapy.^[ii]
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.^[iii] Many
men with non-metastatic CRPC will go on to develop metastatic CRPC.^[iv]

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). Additional ongoing studies, such as the ARCHES trial in
metastatic hormone-sensitive prostate cancer and the EMBARK trial in
non-metastatic hormone-sensitive prostate cancer, are continuing to
evaluate the potential of enzalutamide to help patients in need.

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 a study of patients with predisposing factors,
seizures were reported in 2.2% of patients. See section 5.1 of the
Prescribing Information for the list of predisposing factors. It is
unknown whether anti-epileptic medications will prevent seizures with
XTANDI. 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 placebo-controlled 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 the 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 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
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 for additional safety information.

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 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 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 other cancers. 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 September 14,
2017. 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) and a potential indication in patients with
non-metastatic castration-resistant prostate cancer, including their
potential benefits, 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, the uncertainties inherent in research and
development, including the ability to meet anticipated clinical trial
completion dates and regulatory submission dates, as well as the
possibility of unfavorable clinical trial results, including unfavorable
new clinical data and additional analyses of existing clinical data;the
risk that clinical trial data are subject to differing interpretations,
and, even when we view data as sufficient to support the safety and/or
effectiveness of a product candidate, regulatory authorities may not
share our views and may require additional data or may deny approval
altogether; whether regulatory authorities will be satisfied with the
design of and results from our clinical studies; whether and when any
supplemental drug applications may be filed for XTANDI for the potential
indication; whether and when regulatory authorities may approve any such
applications, which will depend on the assessment by such regulatory
authority of the benefit-risk profile suggested by the totality of the
efficacy and safety information submitted; decisions by regulatory
authorities regarding labeling, safety, and other matters that could
affect the availability or commercial potential of XTANDI; risks related
to 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, 2016 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.

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