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Pfizer and Astellas Amend Clinical Research Protocols for Two Phase 3 Trials of Enzalutamide in Patients with Hormone-Sensitive Prostate Cancer

Amendments accelerate anticipated primary completion dates for both ARCHES and EMBARK trials

Wednesday, August 22, 2018 - 5:00pm
EDT

NEW YORK & TOKYO--(BUSINESS WIRE)--Pfizer Inc. (NYSE:PFE) and Astellas Pharma Inc. (TSE:4503, President and
CEO: Kenji Yasukawa, Ph.D., “Astellas”) today announced amendments to
the protocols for two registrational Phase 3 trials, ARCHES and EMBARK,
designed to evaluate the safety and efficacy of XTANDI®
(enzalutamide) in men with hormone-sensitive prostate cancer (HSPC).
These amendments accelerate timelines for the anticipated primary
completion dates of both trials.

ARCHES is a randomized Phase 3 study evaluating the efficacy and safety
of enzalutamide plus androgen deprivation therapy (ADT) versus ADT alone
in metastatic HSPC patients. The primary endpoint of the trial is
radiographic progression-free survival (rPFS). Changes to the protocol
include revision of the planned analyses of the primary and secondary
endpoints. Enrollment was completed earlier this year. The companies now
anticipate the primary completion date for the ARCHES clinical trial to
be in late 2018. The previously expected primary completion date was
April 2020.

Revisions were also made to the protocol for EMBARK, a randomized Phase
3 study of enzalutamide plus leuprolide, enzalutamide monotherapy, and
leuprolide alone in men with high-risk non-metastatic HSPC. The primary
endpoint of the trial is metastasis-free survival (MFS). The main
purpose of the amendment is to revise the planned analyses of the
primary and several secondary endpoints, which reduced the target sample
size. Enrollment was completed earlier this year. With these changes,
the estimated primary completion date for the EMBARK clinical trial is
mid-2020. Previously, the expected primary completion date for EMBARK
was March 2021.

“We continually strive to design and implement clinical trials that
bring innovations to people with the greatest need,” said Steven Benner,
M.D., senior vice president and global therapeutic area head, Oncology
Development, Astellas. “With the amendments to ARCHES and EMBARK, we
will be able to evaluate the potential of XTANDI for men with
hormone-sensitive prostate cancer sooner, including for those with
non-metastatic disease in which there are no currently approved oral
treatment options.”

“With a large body of evidence demonstrating the activity of XTANDI in
men with castrate-resistant prostate cancer, ARCHES and EMBARK are
designed to extend the evaluation of XTANDI to men with
hormone-sensitive prostate cancer,” said Mace Rothenberg, M.D., chief
development officer, Oncology, Pfizer Global Product Development. “Our
goal is to build upon the body of clinical evidence for enzalutamide in
an effort to help address the unmet needs of an even broader spectrum of
prostate cancer patients.”

XTANDI is approved by the U.S. Food and Drug Administration for the
treatment of castration-resistant prostate cancer.

Details regarding ARCHES (NCT02677896) and EMBARK (NCT02319837) are
available on ClinicalTrials.gov.

About XTANDI

®

 (enzalutamide) capsules

XTANDI
(enzalutamide) is an androgen receptor inhibitor indicated for the
treatment of patients with castration-resistant prostate cancer.

Important Safety Information for XTANDI

®

Warnings and Precautions

Seizure occurred in
0.4% of patients receiving XTANDI in clinical studies. In a study of
patients with predisposing factors for seizure, 2.2% of XTANDI-treated
patients experienced a seizure. Patients in the study had one or more of
the following pre-disposing factors: use of medications that may lower
the seizure threshold; history of traumatic brain or head injury,
cerebrovascular accident or transient ischemic attack, Alzheimer’s
disease, meningioma, or leptomeningeal disease from prostate cancer,
unexplained loss of consciousness within the last 12 months, history of
seizure, presence of a space occupying lesion of the brain, history of
arteriovenous malformation, or history of brain infection. It is unknown
whether anti-epileptic medications will prevent seizures with XTANDI.
Advise patients of the risk of developing a seizure while taking XTANDI
and of engaging in any activity where sudden loss of consciousness could
cause serious harm to themselves or others. 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.

Hypersensitivity reactions, including edema of the face (0.5%),
tongue (0.1%), or lip (0.1%) have been observed with XTANDI in clinical
trials. Pharyngeal edema has been reported in post-marketing cases.
Advise patients who experience any symptoms of hypersensitivity to
temporarily discontinue XTANDI and promptly seek medical care.
Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the placebo-controlled clinical
studies, ischemic heart disease occurred more commonly in patients on
the XTANDI arm compared to patients on the placebo arm (2.7% vs 1.2%).
Grade 3-4 ischemic events occurred in 1.2% of patients on XTANDI versus
0.5% on placebo. Ischemic events led to death in 0.4% of patients on
XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of
ischemic heart disease. Optimize management of cardiovascular risk
factors, such as hypertension, diabetes, or dyslipidemia. Discontinue
XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures In the placebo-controlled clinical studies,
falls occurred in 10% of patients treated with XTANDI compared to 4% of
patients treated with placebo. Fractures occurred in 8% of patients
treated with XTANDI and in 3% of patients treated with placebo. Evaluate
patients for fracture and fall risk. Monitor and manage patients at risk
for fractures according to established treatment guidelines and consider
use of bone-targeted agents.

Embryo-Fetal Toxicity Safety and efficacy of XTANDI have not been
established in females. XTANDI can cause fetal harm and loss of
pregnancy when administered to a pregnant female. Advise males with
female partners of reproductive potential to use effective contraception
during treatment with XTANDI and for 3 months after the last dose of
XTANDI. XTANDI should not be handled by females who are or may become
pregnant.

Adverse Reactions

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

In the placebo-controlled study of metastatic CRPC (mCRPC) 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 mCRPC 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 placebo-controlled study of
non-metastatic CRPC (nmCRPC) patients, Grade 3 or higher adverse
reactions were reported in 31% of XTANDI patients and 23% of placebo
patients. Discontinuations with an adverse event as the primary reason
were reported for 9% of XTANDI patients and 6% of placebo patients. In
the bicalutamide-controlled study of chemotherapy-naïve mCRPC patients,
Grade 3-4 adverse reactions were reported in 39% of XTANDI patients and
38% of bicalutamide patients. Discontinuations with an AE as the primary
reason were reported for 8% of XTANDI patients and 6% of bicalutamide
patients.

Lab Abnormalities: In the two placebo-controlled trials in
patients with mCRPC, Grade 1-4 neutropenia occurred in 15% of XTANDI
patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). In
the placebo-controlled trial in patients with nmCRPC, Grade 1-4
neutropenia occurred in 8% of patients receiving XTANDI (0.5% Grade 3-4)
and in 5% of patients receiving placebo (0.2% Grade 3-4).

Hypertension: In the two placebo-controlled trials in patients
with mCRPC, hypertension was reported in 11% of XTANDI patients and 4%
of placebo patients. Hypertension led to study discontinuation in patients in each arm. In the placebo-controlled trial in patients with
nmCRPC, hypertension was reported in 12% of patients receiving XTANDI
and 5% of patients receiving placebo.

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 Pfizer Oncology

Pfizer Oncology is committed to
pursuing innovative treatments that have a meaningful impact on people
living with cancer. Our growing pipeline of biologics, small molecules,
and immunotherapies is focused on identifying and translating the best
scientific breakthroughs into clinical application for patients across a
diverse array of solid tumors and hematologic cancers. Today, we have 10
approved oncology medicines and 14 assets currently in clinical
development. By maximizing our internal scientific resources and
collaborating with other companies, government and academic
institutions, as well as patients and non-profit and professional
organizations, we are bringing together the brightest and most
enterprising minds to take on the toughest cancers. Together we can
accelerate breakthrough treatments to patients around the world and work
to redefine life with cancer.

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 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 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.

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.

Pfizer Disclosure Notice

The information contained in this
release is as of August 22, 2018. 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 potential new indications being evaluated for the
treatment of men with metastatic hormone-sensitive prostate cancer and
the treatment of men with high-risk non-metastatic hormone-sensitive
prostate cancer, amendments to protocols of the ARCHES and EMBARK
clinical trials and the expected primary completion dates of those
trials, 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, uncertainties regarding the
commercial success of XTANDI; the uncertainties inherent in research and
development, including the ability to meet anticipated clinical trial
commencement and 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; the risks associated with interim data; whether and
when drug applications for any of the potential new indications for
XTANDI will be filed in any jurisdictions; whether and when regulatory
authorities in any jurisdictions may approve any such other
applications, which will depend on the assessment by such regulatory
authorities of the benefit-risk profile suggested by the totality of the
efficacy and safety information submitted and, if approved, whether
XTANDI for any such potential new indications will be commercially
successful; 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, 2017 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.



Contact: 

Pfizer:
For Media
Jessica Smith, 212-733-6213
[email protected]
or
For Investors
Ryan Crowe, 212-733-8160
[email protected]
or
Astellas:
For Media
Colin McBean, 847-420-3421
[email protected]
or
For Investors
Shin Okubo, 81-3-3244-3202
[email protected]