XTANDI is Now FDA-Approved for the Treatment
of Metastatic Castration-Sensitive Prostate Cancer in Addition to
Non-Metastatic and Metastatic Castration-Resistant Prostate
Cancer
Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503,
President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) announced
today that the U.S. Food and Drug Administration (FDA) has approved
a supplemental New Drug Application (sNDA) for XTANDI®
(enzalutamide) for the treatment of patients with metastatic
castration-sensitive prostate cancer (mCSPC). In 2019, it is
estimated that just over 40,000 men in the United States are living
with mCSPC, a form of prostate cancer that has spread to other
parts of the body and still responds to a medical or surgical
treatment that lowers testosterone.1,2,3
With this approval, XTANDI is now the first and only oral
treatment approved by the FDA in three distinct types of advanced
prostate cancer – non-metastatic and metastatic
castration-resistant prostate cancer (CRPC) and mCSPC. The approval
is based on results from ARCHES, a randomized Phase 3 study which
evaluated 1,150 men with mCSPC and met its primary endpoint of
radiographic progression-free survival (rPFS).
“Men with metastatic castration-sensitive prostate cancer face
complex treatment decisions and it is critical for physicians and
patients to have as much information as possible when deciding on
all of the options available,” said Andrew Armstrong, M.D.,
Professor of Medicine, Surgery, Pharmacology and Cancer Biology,
Director of Research in the Duke Cancer Institute’s Center for
Prostate and Urologic Cancers and lead investigator of ARCHES. “The
research supporting the FDA approval and updated treatment
guidelines provide physicians and patients with compelling evidence
to consider enzalutamide as a treatment option for men with this
disease.”
Data from the ARCHES trial demonstrated that the use of XTANDI
plus androgen deprivation therapy (ADT) significantly reduced the
risk of radiographic progression or death by 61 percent compared to
placebo plus ADT (n=1,150; hazard ratio [HR]: 0.39 [95% confidence
interval (CI): 0.30-0.50]; p<0.0001). Overall survival data were
not mature at the time of final rPFS analysis.
The safety analysis of the ARCHES trial is generally consistent
with the safety profile of XTANDI in previous clinical trials in
CRPC. In ARCHES, common adverse reactions (Grade 1 to 4 ARs;
occurring in at least 5% of patients) that were reported more
frequently in patients treated with XTANDI plus ADT vs placebo plus
ADT included hot flush (27% vs 22%), asthenic conditions (24% vs
20%), hypertension (8.0% vs 5.6%), fractures (6.5% vs 4.2%), and
musculoskeletal pain (6.3% vs 4.0%).
“XTANDI has been established as a standard of care for men with
castration-resistant prostate cancer and has been prescribed to
more than 420,000 patients worldwide since it was first approved in
2012,” said Andrew Krivoshik, M.D., Ph.D., Senior Vice President
and Oncology Therapeutic Area Head at Astellas. “This approval in
metastatic castration-sensitive prostate cancer means physicians
can now offer XTANDI to men earlier in their advanced prostate
cancer treatment journey.”
“Today’s approval adds to over a decade of global clinical
research aimed at better understanding the potential benefit of
XTANDI for men with advanced prostate cancer,” said Andy Schmeltz,
Global President, Pfizer Oncology. “The FDA approval marks
continued progress to help meet the needs of patients, including
men living with metastatic castration-sensitive prostate
cancer.”
Pfizer and Astellas are committed to helping patients access
XTANDI by providing them with access and reimbursement support
resources, including information regarding patient healthcare
coverage options and financial assistance options that may be
available to help patients with financial needs. Patients can visit
www.XTANDI.com or call XTANDI Support Solutions at 1-855-898-2634
to learn more.
About Metastatic Castration-Sensitive Prostate Cancer
Prostate cancer is considered metastatic once it has spread
outside of the prostate gland to other parts of the body, such as
the bones, lymph nodes, bladder, and rectum.2 Men are considered
castration- (or hormone-) sensitive if their disease still responds
to medical or surgical treatment to lower testosterone levels.1 The
prevalence of mCSPC in the U.S. in 2019 is estimated to be just
over 40,000.3
ARCHES Trial
The company-sponsored, Phase 3, randomized, double-blind,
placebo-controlled, multi-national ARCHES trial (NCT02677896)
enrolled 1,150 patients with mCSPC at sites in the U.S., Canada,
Europe, South America, and the Asia-Pacific region. Patients in the
trial were randomized to receive XTANDI 160 mg daily or placebo and
continued on a luteinizing hormone-releasing hormone (LHRH) agonist
or antagonist or had a history of bilateral orchiectomy.
The primary endpoint of the trial was rPFS assessed by blinded
independent central review. Radiographic progression-free survival
was defined as the time from randomization to radiographic disease
progression at any time or death within 24 weeks after study drug
discontinuation. Radiographic disease progression was defined by
identification of two or more new bone lesions on a bone scan with
confirmation (Prostate Cancer Working Group 2 criteria) and/or
progression in soft tissue disease. Patients were stratified by
volume of disease (low vs high) and prior docetaxel therapy for
prostate cancer (no prior docetaxel, 1-5 cycles, or 6 prior
cycles).
About XTANDI® (enzalutamide)
XTANDI (enzalutamide) is an androgen receptor inhibitor
indicated for the treatment of patients with castration-resistant
prostate cancer (CRPC) and metastatic castration-sensitive prostate
cancer (mCSPC).
Important Safety Information for XTANDI®
Warnings and Precautions
Seizure occurred 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 weight loss.
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
placebo patients.
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
hypercalcemia.
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 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 the Enzalutamide Development Program
As part of Pfizer and Astellas' ongoing commitment to the
clinical development of enzalutamide, XTANDI is also being
evaluated in the EMBARK trial, in men with high-risk non-metastatic
CSPC. Details about EMBARK (NCT02319837) are available on
www.clinicaltrials.gov.
The European Medicines Agency (EMA) and the Pharmaceuticals and
Medical Devices Agency (PMDA) in Japan are currently evaluating
XTANDI for men with metastatic hormone-sensitive prostate
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 Pfizer Oncology
At Pfizer Oncology, we are committed to advancing medicines
wherever we believe we can make a meaningful difference in the
lives of patients. Today, Pfizer Oncology has an industry-leading
portfolio of 22 approved innovative cancer medicines and
biosimilars across more than 30 indications, including breast,
prostate, kidney and lung cancers, as well as leukemia and
melanoma. Pfizer Oncology is striving to change the trajectory of
cancer.
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 December 16,
2019. 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 new indication in the U.S. for the treatment
of men with metastatic castration-sensitive 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, 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 our 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 our clinical studies; whether and
when drug applications for the new indication for XTANDI may be
filed in any other jurisdictions and whether and when drug
applications for any other potential indications for XTANDI may be
filed in any jurisdictions; whether and when regulatory authorities
in any jurisdictions may approve any such other applications that
may be pending or filed (including the applications under review by
the EMA and PMDA in Japan for the new indication), which will
depend on myriad 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 new indication; 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, 2018 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.
____________________________
1 Cancer.net. Prostate Cancer: Types of Treatment (03-2018).
https://www.cancer.net/cancer-types/prostate-cancer/types-treatment.
Accessed 912-2019.
2 American Society of Clinical Oncology. ASCO Answers: Prostate
Cancer (2018).
http://www.cancer.net/sites/cancer.net/files/asco_answers_guide_prostate.pdf.
Accessed 10-07-2019.
3 Supplement to: Scher HI, Solo K, Valant J, Todd MB, Mehra M.
Prevalence of prostate cancer clinical states and mortality in the
United States: estimates using a dynamic progression model. PLoS
One 2015;10(10):e0139440.
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version on businesswire.com: https://www.businesswire.com/news/home/20191216005826/en/
Pfizer: For Media Jessica Smith 212-733-6213
jessica.smith2@pfizer.com
For Investors Ryan Crowe 212-733-8160 ryan.crowe@pfizer.com
Astellas: For Media Chris Goldrick 847-224-3014
chris.goldrick@astellas.com
For Investors Shin Okubo 81-3-3244-3202
shin.ohkubo@astellas.com
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