Pfizer and Astellas announce positive topline results from
Phase 3 EMBARK trial
YORK and TOKYO,
2023 /PRNewswire/ -- Pfizer Inc. (NYSE: PFE) and
Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today
announced positive topline results from the Phase 3 EMBARK trial
evaluating XTANDI® (enzalutamide) in men with
non-metastatic hormone-sensitive prostate cancer (nmHSPC; also
known as non-metastatic castration-sensitive prostate cancer or
nmCSPC) with high-risk biochemical recurrence (BCR). Patients
enrolled in the trial were randomized to one of three study arms:
XTANDI plus leuprolide, placebo plus leuprolide, or XTANDI
monotherapy. The study met its primary endpoint with a
statistically significant and clinically meaningful improvement in
metastasis-free survival (MFS) for patients treated with XTANDI
plus leuprolide versus placebo plus leuprolide.
At the time of the analysis, a positive trend in the key
secondary endpoint of overall survival (OS) was also observed, but
these data were not yet mature. Patients in the trial will be
followed for a subsequent final OS analysis. The study also met a
key secondary endpoint with a statistically significant and
clinically meaningful improvement in MFS for patients treated with
XTANDI monotherapy versus placebo plus leuprolide. Additional key
secondary endpoints reached statistical significance, including
time to prostate-specific antigen (PSA) progression and time to
first use of new antineoplastic therapy. Other secondary endpoints
are being analyzed. No new safety signals have been observed to
date in the preliminary safety analysis, which is consistent with
the established safety profile of XTANDI.
"As the only novel hormone therapy approved for three disease
states of prostate cancer in the U.S., XTANDI has impacted hundreds
of thousands of men," said Chris
Boshoff, M.D., Ph.D., Chief Development Officer, Oncology
and Rare Disease, Pfizer Global Product Development. "The topline
findings from EMBARK are highly encouraging and we look forward to
engaging with health authorities to potentially bring XTANDI to men
with non-metastatic hormone-sensitive prostate cancer with
high-risk biochemical recurrence."
"While current treatment options for localized prostate cancer
are intended to be curative, some men remain at higher risk for
biochemical recurrence following primary treatment, which may
result in metastases," said Ahsan Arozullah, M.D., MPH, Senior Vice
President and Head of Development Therapeutic Areas, Astellas. "The
EMBARK trial is the first study to demonstrate a statistically
significant improvement in MFS using the combination of XTANDI plus
leuprolide in men with this stage of disease."
Detailed results from EMBARK will be presented at a future
medical meeting. These data will also be discussed with regulatory
authorities, including the U.S. Food and Drug Administration (FDA),
to support a potential regulatory submission for XTANDI in this
The Phase 3, randomized, double-blind,
placebo-controlled, multi-national trial enrolled 1,068 patients
with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also
known as non-metastatic castration-sensitive prostate cancer or
nmCSPC) with high-risk biochemical recurrence (BCR) at sites
in the United States, Canada, Europe, South
America, and the Asia-Pacific region. Patients who were
considered high-risk BCR had a prostate-specific antigen (PSA)
doubling time ≤ 9 months, serum testosterone ≥ 150 ng/dL (5.2
nmol/L), and screening PSA by the central laboratory ≥ 1 ng/mL if
they had a radical prostatectomy (with or without radiotherapy) as
primary treatment for prostate cancer or at least 2 ng/mL above the
nadir if they had radiotherapy only as primary treatment for
prostate cancer. Patients in the EMBARK trial were randomized to
receive enzalutamide 160 mg daily plus leuprolide, enzalutamide 160
mg as a monotherapy, or placebo plus leuprolide.
The primary endpoint of the trial was metastasis-free survival
(MFS) for enzalutamide plus leuprolide and placebo plus leuprolide.
MFS is defined as the duration of time in months between
randomization and the earliest objective evidence of radiographic
progression by central imaging or death. For more information on
the EMBARK (NCT02319837) trial go to www.clinicaltrials.gov.
XTANDI has not been approved for the treatment of patients with
nmHSPC with high-risk BCR.
About Non-Metastatic Hormone-Sensitive Prostate Cancer with
High-Risk Biochemical Recurrence
hormone- (or castration-) sensitive prostate cancer (nmHSPC or
nmCSPC) means there is no detectable evidence of the cancer
spreading to distant parts of the body (metastases) with
conventional radiological methods (CT/MRI) and the cancer still
responds to medical or surgical treatment to lower testosterone
levels.1,2 Of men who have undergone definitive
prostate cancer treatment, including radical prostatectomy,
radiotherapy, or both, an estimated 20-40% will experience a
biochemical recurrence (BCR) within 10 years.3 About 9
out of 10 men with high-risk BCR will develop metastatic disease,
and 1 in 3 will die as a result of the recurrence.3 The
EMBARK trial focused on men with high-risk BCR. Per the EMBARK
protocol, patients with nmHSPC with high-risk BCR are those
initially treated by radical prostatectomy or radiotherapy, or
both, with a PSA doubling time ≤ 9 months. High-risk BCR patients
with a PSA doubling time of ≤ 9 months have a higher risk of
metastases and death.4
(enzalutamide) is an androgen receptor signaling inhibitor. The
recommended dosage of XTANDI is 160 mg (capsules or tablets)
administered orally once daily with or without food. XTANDI is a
standard of care that has received regulatory approvals for use in
men with mHSPC, mCRPC, and nmCRPC in the
United States and for one or more of these indications in
more than 100 countries, including the European Union and
Japan. More than 720,000 patients
have been treated with XTANDI globally.5
E.U. Important Safety Information
indicated in the European Union for the treatment of adult men
1. Metastatic hormone-sensitive prostate
cancer (mHSPC) in combination with androgen deprivation therapy
2. High-risk non-metastatic castration-resistant prostate
3. Metastatic CRPC who are asymptomatic or mildly symptomatic
after failure of ADT in whom chemotherapy is not yet clinically
indicated. It is also indicated in adult men with metastatic CRPC
whose disease has progressed on or after docetaxel therapy.
For Important Safety Information for enzalutamide please see the
full Summary of Product Characteristics at:
U.S. Important Safety Information
(enzalutamide) is indicated in the U.S. for the treatment of
patients with castration-resistant prostate cancer (CRPC) and
metastatic castration-sensitive prostate cancer (mCSPC).
Warnings and Precautions
in 0.5% of patients receiving XTANDI in seven randomized clinical
trials. In a study of patients with predisposing factors for
seizure, 2.2% of XTANDI-treated patients experienced a seizure. It
is unknown whether anti-epileptic medications will prevent seizures
with XTANDI. Patients in the study had one or more of the following
predisposing factors: use of medications that may lower the seizure
threshold, history of traumatic brain or head injury, history of
cerebrovascular accident or transient ischemic attack, and
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. 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) There have been reports of PRES in patients
receiving XTANDI. PRES is a neurological disorder that 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 seven randomized 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 combined data of four
randomized, placebo-controlled clinical studies, ischemic heart
disease occurred more commonly in patients on the XTANDI arm
compared to patients on the placebo arm (2.9% vs 1.3%). Grade 3-4
ischemic events occurred in 1.4% of patients on XTANDI versus 0.7%
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 occurred in patients receiving
XTANDI. 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. In
the combined data of four randomized, placebo-controlled clinical
studies, falls occurred in 11% of patients treated with XTANDI
compared to 4% of patients treated with placebo. Fractures occurred
in 10% of patients treated with XTANDI and in 4% of patients
treated with placebo.
Embryo-Fetal Toxicity The 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.
Adverse Reactions (ARs) In the data from the four
randomized placebo-controlled trials, the most common ARs (≥ 10%)
that occurred more frequently (≥ 2% over placebo) in XTANDI-treated
patients were asthenia/fatigue, back pain, hot flush, constipation,
arthralgia, decreased appetite, diarrhea, and hypertension. In the
bicalutamide-controlled study, the most common ARs (≥ 10%) reported
in XTANDI-treated patients were asthenia/fatigue, back pain,
musculoskeletal pain, hot flush, hypertension, nausea,
constipation, diarrhea, upper respiratory tract infection, and
In AFFIRM, the placebo-controlled study of metastatic CRPC
(mCRPC) patients who previously received docetaxel, Grade 3 and
higher ARs were reported among 47% of XTANDI-treated patients.
Discontinuations due to adverse events (AEs) were reported for 16%
of XTANDI-treated patients. In PREVAIL, the placebo-controlled
study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 44% of XTANDI patients and
37% of placebo patients. Discontinuations due to AEs were reported
for 6% of XTANDI treated patients. In TERRAIN, the
bicalutamide-controlled study of chemotherapy-naive mCRPC patients,
Grade 3-4 ARs 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.
In PROSPER, the placebo-controlled study of non-metastatic CRPC
(nmCRPC) patients, Grade 3 or higher ARs were reported in 31% of
XTANDI patients and 23% of placebo patients. Discontinuations with
an AE as the primary reason were reported for 9% of XTANDI patients
and 6% of placebo patients.
In ARCHES, the placebo-controlled study of metastatic CSPC
(mCSPC) patients, Grade 3 or higher AEs were reported in 24% of
XTANDI-treated patients. Permanent discontinuation due to AEs as
the primary reason was reported in 5% of XTANDI patients and 4% of
Lab Abnormalities: Lab abnormalities that occurred in ≥
5% of patients, and more frequently (> 2%) in the XTANDI arm
compared to placebo in the pooled, randomized, placebo-controlled
studies are neutrophil count decreased, white blood cell decreased,
hyperglycemia, hypermagnesemia, hyponatremia, and
Hypertension: In the combined data from four
randomized placebo-controlled clinical trials, hypertension was
reported in 12% of XTANDI patients and 5% of placebo patients.
Hypertension led to study discontinuation in < 1% of patients in
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 coadministration 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
About Pfizer Oncology
At Pfizer Oncology, we are
committed to advancing medicines wherever we believe we can make a
meaningful difference in the lives of people living with cancer.
Today, we have an industry-leading portfolio of 24 approved
innovative cancer medicines and biosimilars that generated
$12.1 billion in revenue in 2022,
including the best-selling therapies for metastatic breast cancer
and prostate cancer. Our in-line portfolio is focused on four
broad, key areas where we have pioneered several breakthroughs:
breast cancer, genitourinary cancer, hematology, and precision
medicine, and we are advancing an extensive pipeline of 33 programs
in clinical development.
Astellas Pharma Inc. is a
pharmaceutical company conducting business in more than 70
countries around the world. We are promoting the Focus Area
Approach that is designed to identify opportunities for the
continuous creation of new drugs to address diseases with high
unmet medical needs by focusing on Biology and Modality.
Furthermore, we are also looking beyond our foundational Rx focus
to create Rx+® healthcare solutions that combine our expertise and
knowledge with cutting-edge technology in different fields of
external partners. Through these efforts, Astellas stands on the
forefront of healthcare change to turn innovative science into
VALUE for patients. For more information, please visit our website
About the Pfizer/Astellas Collaboration
October 2009, Medivation, Inc., which
is now part of Pfizer (NYSE:PFE), and Astellas (TSE: 4503) entered
into a commercial agreement to jointly develop and commercialize
XTANDI® (enzalutamide) in the
United States, while Astellas has responsibility for
manufacturing and all additional regulatory filings globally, as
well as commercializing the product outside the United States. Pfizer receives alliance
revenues as a share of U.S. profits and receives royalties on sales
outside the U.S.
Pfizer Disclosure Notice
The information contained in
this release is as of March 16, 2023.
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 indication
being evaluated for the treatment of men with non-metastatic
hormone-sensitive prostate cancer with high-risk biochemical
recurrence (BCR), 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 endpoints, commencement and/or
completion dates for clinical trials, regulatory submission dates,
regulatory approval dates and/or launch dates, as well as the
possibility of unfavorable new clinical data and further analyses
of existing clinical data; the risk that clinical trial data are
subject to differing interpretations and assessments by regulatory
authorities; whether regulatory authorities will be satisfied with
the design of and results from the clinical studies; whether and
when drug applications for any of the potential new indications for
XTANDI or any potential indications for XTANDI may be filed in any
jurisdictions; whether and when regulatory authorities in any
jurisdictions may approve any such applications, which will depend
on a myriad of factors, including making a determination as to
whether the product's benefits outweigh its known risks and
determination of the product's efficacy and, if approved, whether
XTANDI for any such potential new indications will be commercially
successful; decisions by regulatory authorities impacting labeling,
manufacturing processes, safety, and/or other matters that could
affect the availability or commercial potential of XTANDI,
including for the potential new indications; dependence on the
efforts and funding by Astellas Pharma Inc. for the development,
manufacturing and commercialization of XTANDI; uncertainties
regarding the impact of COVID-19 on Pfizer's business, operations
and financial results; 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, 2022 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
1 Cancer.net. Prostate Cancer: Types of Treatment
Accessed March 16, 2023.
2 American Society of Clinical Oncology. ASCO Answers:
Prostate Cancer (2021).
Accessed March 16, 2023.
3 Ward JF, Moul JW. Rising prostate-specific antigen
after primary prostate cancer therapy. Nat Clin Pract Urol. 2005
Apr;2(4):174-82. doi: 10.1038/ncpuro0145. PMID: 16474760.
4 Paller, Channing J et al. "Management of patients with
biochemical recurrence after local therapy for prostate cancer."
Hematology/oncology clinics of North
America vol. 27,6 (2013): 1205-19, viii.
5 Data on file. Northbrook,
IL: Astellas Inc.
View original content to download
SOURCE Astellas Pharma Inc.; Pfizer Inc.