TOKYO, Nov. 25, 2019 /PRNewswire/ -- Astellas
Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today
announced that the China National Medical Products Administration
(NMPA) approved a new drug application (NDA) for XTANDI®
(enzalutamide) on November 18 for the
treatment of adult men with metastatic castration-resistant
prostate cancer (CRPC) who are asymptomatic or mildly symptomatic
after failure of androgen deprivation therapy (ADT) in whom
chemotherapy is not yet clinically indicated.
The approval by the NMPA was based on the results of an Asian
multinational Phase 3, randomized, double-blind, placebo controlled
efficacy and safety study of enzalutamide in asymptomatic or mildly
symptomatic patients with progressive metastatic prostate cancer
who had disease progression despite ADT and a single-dose
pharmacokinetic study in healthy Chinese volunteers (Protocol
9785-CL-0013).1
The study, Asian PREVAIL (also known as
9785-CL-0232), evaluated oral enzalutamide (160 mg/day) versus
placebo plus gonadotropin-releasing hormone (GnRH) therapy or after
bilateral orchiectomy. The study, involving Asian patients
including approximately 200 Chinese patients, showed consistent
results with those in the global pivotal Phase 3 PREVAIL study in
the same target population.2
"Currently the treatment options are limited in China for men with metastatic
castration-resistant prostate cancer," said Andrew Krivoshik, M.D., Ph.D., Senior Vice
President and Global Therapeutic Area Head, Oncology Development,
Astellas. "The approval of enzalutamide in China brings us one step closer to offering
physicians a meaningful treatment option in an area where there is
a high medical need."
Patients treated with enzalutamide demonstrated a statistically
significant reduction in the risk of Prostate Specific Antigen
(PSA) progression (Hazard Ratio of 0.38 [95% confidence interval:
0.27, 0.52], P < 0.0001). The median time to PSA progression was
8.31 months in the enzalutamide group versus 2.86 months in the
placebo group. Treatment with enzalutamide also resulted in a
statistically significant reduction in risk of radiographic disease
progression or death compared with treatment with placebo with a
Hazard Ratio (HR) of 0.31 (95% confidence interval: 0.20, 0.46;
P<0.0001). Additionally, treatment with enzalutamide showed a
statistically significant improvement in overall survival compared
to treatment with placebo, with a 67% decrease in the risk of death
(HR 0.33, [95% CI: 0.16, 0.67]; P=0.0015).
The safety profile observed in the Asian PREVAIL study was
generally consistent with previous clinical studies in patients
with metastatic CRPC.2 The most common adverse reactions
(≥10%) that occurred more frequently (≥2% over placebo) in the
enzalutamide-treated patients from the randomized
placebo-controlled clinical trials were asthenia/fatigue, decreased
appetite, hot flush, arthralgia, dizziness/vertigo, hypertension,
headache, and decreased weight.
In addition to the Asian PREVAIL data involving a Chinese
sub-population, the approval was supported by results from the
global Phase 3 PREVAIL trial, which were published in the New
England Journal of Medicine in 2014. The Phase 3 PREVAIL trial
was a randomized, double-blind, placebo-controlled, multi-national
trial that enrolled more than 1,700 patients at sites in
the United States, Canada, Europe, Australia, Russia, Israel and Asia including Japan.2
Enzalutamide is a standard of care for men with metastatic CRPC
in countries where it is available. Since 2012, it has been
prescribed to more than 420,000 patients worldwide.3
Prostate cancer is the second most common cancer in men
worldwide4 and in China
it has become the most common tumor in male urinary
malignancies.5
"The approval of enzalutamide is an important milestone. Tens of
thousands of Chinese patients with metastatic castration-resistant
prostate cancer could potentially benefit from the reduced risk of
disease progression and death found in the Asian PREVAIL study,"
said Hiroshi Hamaguchi, President,
Astellas Greater China Commercial. "The approval also demonstrates
a significant step forward for Astellas, with enzalutamide being
the first Astellas oncology treatment approved in China."
About Asian PREVAIL (9785-CL-0232)
The Asian PREVAIL
study involving a Chinese sub-population was a multinational Phase
3, randomized, double-blind, placebo-controlled efficacy and safety
study of oral enzalutamide (formerly MDV3100) in asymptomatic or
mildly symptomatic participants with progressive metastatic
prostate cancer who have disease progression despite ADT. The study
enrolled 388 participants who were not previously treated with
cytotoxic chemotherapy. The trial was designed to evaluate
enzalutamide at a dose of 160 mg taken orally once daily on time to
PSA progression as compared to placebo in chemotherapy-naïve
participants with progressive metastatic prostate cancer who had
failed ADT. The study completed its double-blind period and is now
in the open-label period.
About metastatic Castration-Resistant Prostate
Cancer
Prostate cancer is considered metastatic once
the cancer has spread outside of the prostate gland to other parts
of the body.6 Metastatic CRPC is fatal,
with a median survival of approximately 3-4 years for men starting
treatment with ADT.7
About
Enzalutamide8
Enzalutamide is an
oral, once-daily androgen receptor signaling inhibitor.
Enzalutamide directly targets the androgen receptors (AR) and
exerts its effects on three steps of the AR signaling pathway:
- Inhibits androgen binding: Androgen binding induces a
conformational change that triggers activation of the receptor
- Prevents nuclear translocation: Translocation of the AR to the
nucleus is an essential step in AR-mediated gene regulation
- Impairs DNA binding: Binding of the AR to the DNA is essential
for modulation of gene expression
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
enzalutamide in the United States
and Astellas has responsibility for manufacturing and all
additional regulatory filings globally, as well as commercializing
enzalutamide outside the United
States.
Cautionary Notes
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.
References:
_____________________________
1 An Asian Study to Evaluate Efficacy and Safety of
Oral Enzalutamide in Progressive Metastatic Prostate Cancer
Participants
https://clinicaltrials.gov/ct2/show/NCT02294461?term=9785-CL-0232&rank=1.
Last accessed September 2019.
2 Beer T, Armstrong A et al.
Enzalutamide in Metastatic Prostate Cancer before
Chemotherapy. N Engl J Med 2014; 371:424-433.
3 Data on file. Northbrook, IL: Astellas
Inc.
4 American Cancer Society. Key Statistics for
Prostate Cancer.
https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html.
Last accessed September 2019.
5 Chinese guidelines for diagnosis and treatment of
prostate cancer 2018. Chin J Cancer Res. 2019 Feb; 31(1):
67–83.
6 American Society of Clinical Oncology. ASCO
Answers: Prostate Cancer (2018).
http://www.cancer.net/sites/cancer.net/files/asco_answers_guide_prostate.pdf.
Last accessed November 2019.
7 Mottet N, et al. Updated Guidelines for
Metastatic Hormone-sensitive Prostate Cancer: Abiraterone Acetate
Combined with Castration Is Another Standard. Eur Urol.
2018;3:316-321.
8 European Medicines Agency. Summary of Product
Characteristics: Xtandi 40 mg soft capsules.
http://ec.europa.eu/health/documents/community-register/2018/20181023142671/anx_142671_en.pdf.
Last accessed October 2019.
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