- Enzalutamide is the first androgen
receptor-inhibitor to demonstrate a statistically significant
improvement in metastasis-free survival (MFS) in this patient
population in a randomized, controlled clinical trial
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.
[i]
American Cancer Society. Key Statistics
for Prostate Cancer (01-05-2017).
https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html.
Accessed 01-31-2017.
[ii]
Urology Care Foundation. Advanced Prostate
Cancer Patient Guide. www.urologyhealth.org/educational-materials.
Accessed 02-16-2017.
[iii] Luo J, Beer T, Graff J. Treatment of Non-metastatic
Castration Resistant Prostate Cancer. Oncology. April 2016,
30(4):336-344. [iv] Kirby M, Hirst C, Crawford ED. Characterising
the castration-resistant prostate cancer population: a systematic
review. Int J Clin Pract 2011;65(11):1180-1192.
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Pfizer:For MediaSally Beatty,
212-733-6566sally.beatty@pfizer.comorFor InvestorsChuck Triano,
212-733-3901charles.e.triano@pfizer.comorAstellas:For
MediaTyler Marciniak, 847-736-7145tyler.marciniak@astellas.comorFor
InvestorsSo Sekine, 847-224-9557sou.sekine@astellas.com