sNDA Seeks to Expand the Indication of XTANDI to include Men with
Non-metastatic CRPC
NEW YORK & TOKYO--(BUSINESS WIRE)--
Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President
and CEO: Yoshihiko Hatanaka, “Astellas”) announced today that a
supplemental New Drug Application (sNDA) for XTANDI®
(enzalutamide) has been accepted for filing and granted Priority Review
designation by the U.S. Food and Drug Administration (FDA). If approved,
the sNDA would expand the indication of XTANDI to include men with
non-metastatic Castration-Resistant Prostate Cancer (CRPC), based on
data from the Phase 3 PROSPER trial. XTANDI is currently indicated for
the treatment of patients with metastatic CRPC.
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The FDA grants Priority Review designation to applications for drugs
that, if approved, may offer significant improvements in the safety and
effectiveness of the treatment of serious conditions when compared to
standard applications. Under Priority Review, the FDA aims to take
action on an application within six months of receipt, as compared to
ten months under standard review. The Prescription Drug User Fee Act
(PDUFA) goal date assigned by the FDA is July 2018. In addition, the
European Medicines Agency (EMA) has validated the Type II Variation
submitted for XTANDI seeking to expand the current indication to the
same patient population and started the review process on March 5.
“Once cancer spreads and metastasizes, men with castration-resistant
prostate cancer face a daunting prognosis and challenging odds,” said
Steven Benner, M.D., senior vice president and global therapeutic area
head, Oncology Development, Astellas. “We’re pleased to see the FDA’s
Priority Review designation as we work to potentially bring XTANDI to
men living with non-metastatic CRPC.”
“Treatment options have been limited for men with non-metastatic CRPC,
in whom the only evidence of progressive disease is a rapidly rising
PSA,” 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. This milestone marks an
important step toward our ability to bring XTANDI to CRPC patients in an
earlier setting.”
The PROSPER trial evaluated XTANDI plus androgen deprivation therapy
(ADT) versus ADT alone in 1,401 patients with non-metastatic CRPC. The
study met its primary endpoint, demonstrating that the use of XTANDI
plus ADT significantly reduced the risk of developing metastasis or
death compared to ADT alone. Adverse events in the PROSPER trial were
higher in the enzalutamide plus ADT arm compared to ADT alone (87% vs.
77%), and were generally consistent with those reported in prior
enzalutamide clinical trials in patients with metastatic CRPC. Results
from the PROSPER trial were presented at the 2018 Genitourinary Cancers
Symposium (ASCO GU) in February.1 For more information on the
PROSPER trial, go to www.clinicaltrials.gov.
The FDA approved XTANDI in 2012 for the treatment of patients with
metastatic CRPC who had previously received docetaxel. In 2014, the FDA
approved XTANDI to treat patients with metastatic CRPC.
About Prostate Cancer
Prostate cancer is the second most common cancer in men worldwide.2
More than 164,000 men in the United States are estimated to be newly
diagnosed with prostate cancer in 2018.3 In the European
Union, the estimated number of new prostate cancer cases in 2015 was
365,000.4
Castration-resistant prostate cancer (CRPC) refers to the subset of men
whose prostate cancer progresses despite castration levels of
testosterone.5 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.6 Many men with non-metastatic CRPC and a rapidly
rising PSA level go on to develop metastatic CRPC.7
About XTANDI® (enzalutamide) capsules
XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for
the treatment of patients with metastatic castration-resistant prostate
cancer.
Important Safety Information for XTANDI®
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 the Enzalutamide Development Program
Pfizer and Astellas are collaborating on a comprehensive development
program that includes studies of enzalutamide across the full spectrum
of advanced prostate cancer. Ongoing studies of enzalutamide in prostate
cancer include the ARCHES trial in metastatic hormone-sensitive prostate
cancer and the EMBARK trial in non-metastatic hormone-sensitive prostate
cancer.
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 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 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.
Pfizer Disclosure Notice
The information contained in this release is as of March 19, 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 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; the risks associated
with interim data; whether and when any supplemental drug applications
may be filed for XTANDI for the potential indication in any other
jurisdictions; whether and when the FDA and the EMA may approve the
pending applications and whether and when regulatory authorities in any
other 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 the
potential indication 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.
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.
_________________________
1 Hussain M, Fizazi K, Saad F,
et al. PROSPER: a phase 3, randomized, double-blind, placebo
(PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic
castration-resistant prostate cancer (M0 CRPC). ASCO GU Meeting Library. https://meetinglibrary.asco.org/record/157683/abstract.
Accessed 02-07-2018.
2 American Cancer Society. Global
Cancer Facts and Figures (2015). https://www.cancer.org/content/dam/cancerorg/research/cancer-factsand-statistics/global-cancerfacts-and-figures/globalcancer-facts-and-figures-3rdedition.pdf.
Accessed 01-11-2018.
3 American Cancer Society. Key
Statistics for Prostate Cancer. https://www.cancer.org/cancer/prostate-cancer/about/keystatistics.html.
Accessed 01-08-2018.
4 European Commission. Epidemiology
of prostate cancer in Europe (03-17-2017). https://ec.europa.eu/jrc/en/publication/epidemiology-prostate-cancereurope.
Accessed 01-19-2018.
5 Kirby M, Hirst C, Crawford ED.
Characterising the castration resistant prostate cancer population: a
systematic review. Int J Clin Pract 2011;65(11):1180-92.
6
Luo J, Beer T, Graff J. Treatment of nonmetastatic castration-resistant
prostate cancer. Oncology 2016;30(4):336-44.
7
Smith MR, Kabbinavar F, Saad F, Hussain A et al. Natural history of
rising serum prostate-specific antigen in men with castrate
nonmetastatic prostate cancer. J Clin Oncol 2005;23:2918–2925.
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Source: Pfizer Inc.