SAN FRANCISCO and TOKYO, September 11,
2014 /PRNewswire/ --
Approval based on improved overall
survival, delayed time to radiographic progression and an overall
positive benefit-risk profile
Medivation, Inc. (Nasdaq: MDVN) and Astellas Pharma Inc.
(Tokyo: 4503) have announced that
the U.S. Food and Drug Administration (FDA) has approved a new
indication for the use of XTANDI® (enzalutamide)
capsules to treat patients with metastatic castration-resistant
prostate cancer (CRPC). This new approved use follows a priority
review of the supplemental New Drug Application (sNDA) that was
based on results of the Phase 3 PREVAIL trial.
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The FDA initially approved XTANDI, an oral, once-daily androgen
receptor inhibitor, in August 2012
for use in patients with metastatic CRPC who previously received
docetaxel (chemotherapy). The new indication approves XTANDI for
use in men with metastatic CRPC who have not received chemotherapy.
Metastatic CRPC is defined as a cancer that has spread beyond the
prostate gland and has progressed despite treatment to lower
testosterone (i.e., with a gonadotropin-releasing hormone (GnRH)
therapy or with removal of the testes).
"The FDA's priority review and approval of this new indication
for XTANDI now enables the use of an important therapy by patients
with metastatic castration-resistant prostate cancer at all stages
of their disease," said Sef
Kurstjens, M.D., Ph.D., chief medical officer of Astellas
Pharma Inc. and president of Astellas Pharma Global Development,
Inc. "We are pleased that these patients now have XTANDI
available as a treatment option."
"All of us at Medivation extend our thanks to the clinicians and
patients who participated in the PREVAIL clinical trial culminating
in today's approval," said David
Hung, M.D., founder, president and chief executive officer,
Medivation, Inc. "As a company dedicated to the rapid
development of novel therapies to treat serious diseases, we are
pleased to see XTANDI approved in this important patient
population."
In the Phase 3 PREVAIL trial, men receiving XTANDI and GnRH
therapy exhibited a statistically significant improvement in both
overall survival and delayed time to radiographic progression or
death as compared to those on placebo and GnRH therapy.
- XTANDI significantly reduced the risk of radiographic
progression or death by 83% compared with placebo (HR=0.17; p <
0.0001).
- XTANDI significantly reduced the risk of death by 29% compared
with placebo (HR=0.71; p < 0.0001).
When compared to placebo, treatment with XTANDI also delayed
time to initiation of chemotherapy and time to a skeletal related
event.
The safety profile for XTANDI was updated to reflect data from
both the AFFIRM and PREVAIL Phase 3 trials.
- Seizure occurred in 0.9% of patients receiving XTANDI who
previously received docetaxel and 0.1% of patients who were
chemotherapy-naive.
- The most common adverse reactions (≥ 10%) that occurred more
commonly (≥ 2% over placebo) in the XTANDI-treated patients from
the two randomized 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.
"Enzalutamide has been studied and is approved for patients with
metastatic prostate cancer that is resistant to primary hormonal
therapy, a disease state we call castration-resistant prostate
cancer. In this setting, enzalutamide has been shown to extend
overall survival and significantly delay the progression of
prostate cancer," said Tomasz M.
Beer, M.D., F.A.C.P., co-principal investigator of the
PREVAIL study, deputy director of the Knight Cancer Institute and
professor of medicine at Oregon Health & Science University.
"Furthermore, in the PREVAIL trial, the median time to initiating
chemotherapy was delayed by 17 months with enzalutamide treatment
as compared to placebo, so the result is a meaningful period of
time during which men have their disease controlled without the
need for chemotherapy."
A variation application to amend the European Marketing
Authorisation Application based on the results of PREVAIL was
validated for review by the European Medicines Agency on
April 24, 2014.
The approval of this new indication for XTANDI triggers
$90 million in milestone payments to
Medivation under its collaboration agreement with Astellas.
Note to Editors:
Enzalutamide Mechanism of Action
Enzalutamide is an androgen receptor inhibitor that acts on
three different steps in the androgen receptor signaling
pathway.
About
XTANDI® (enzalutamide)capsules
XTANDI (enzalutamide) was approved by the FDA on September 10, 2014 for the treatment of patients
with metastatic CRPC.
Important Safety Information
Contraindications: XTANDI (enzalutamide) capsules can
cause fetal harm when administered to a pregnant woman based on its
mechanism of action and findings in animals. XTANDI is not
indicated for use in women. XTANDI is contraindicated in women who
are or may become pregnant.
Warnings and Precautions: In Study 1, conducted in
patients with metastatic castration-resistant prostate cancer
(CRPC) who previously received docetaxel, seizure occurred in 0.9%
of patients who were treated with XTANDI and 0% treated with
placebo. In Study 2, conducted in patients with chemotherapy-naïve
metastatic CRPC, seizure occurred in 0.1% of patients who were
treated with XTANDI and 0.1% treated with placebo. Patients
experiencing a seizure were permanently discontinued from therapy
and all seizure events resolved. There is no clinical trial
experience re‐administering XTANDI to patients who experienced a
seizure, and limited clinical trial experience in patients with
predisposing factors for seizure. Study 1 excluded the use of
concomitant medications that may lower threshold, whereas Study 2
permitted the use of these medications. Because of the risk of
seizure associated with XTANDI use, patients should be advised of
the risk of engaging in any activity during which sudden loss of
consciousness could cause serious harm to themselves or others.
Permanently discontinue XTANDI in patients who develop a seizure
during treatment.
Adverse Reactions: The most common adverse reactions (≥
10%) reported from the two combined clinical trials that occurred
more commonly (≥ 2% over placebo) in the XTANDI-treated patients
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.
Other Adverse Reactions include:
• Laboratory Abnormalities: In the two studies, Grade 1‐4
neutropenia occurred in 15% of patients treated with XTANDI (1%
Grade 3-4) and in 6% of patients treated with placebo (0.5% Grade
3-4). The incidence of Grade 1‐4 thrombocytopenia was 6% of
patients treated with XTANDI (0.3% Grade 3-4) and 5% of patients on
placebo (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in
10% of patients treated with XTANDI (0.2% Grade 3-4) and 16% of
patients treated with placebo (0.2% Grade 3-4). Grade 1-4
elevations in bilirubin occurred in 3% of patients treated with
XTANDI (0.1% Grade 3-4) and 2% of patients treated with placebo (no
Grade 3-4).
• Infections: In Study 1, 1% of XTANDI versus 0.3% of placebo
patients and in Study 2, 1 patient in each treatment group (0.1%)
had an infection resulting in death.
• Falls: In the two studies, falls including fall‐related
injuries occurred in 9% of XTANDI patients vs 4% treated with
placebo. 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: In the two studies, hypertension was reported in
11% of patients receiving XTANDI and 4% of patients receiving
placebo. No patients experienced hypertensive crisis. Medical
history of hypertension was balanced between arms. Hypertension led
to study discontinuation in < 1% of XTANDI or placebo treated
patients.
Drug Interactions:
• Effect of Other Drugs on XTANDI ‐ Administration of
strong CYP2C8 inhibitors can increase the plasma exposure to
XTANDI. Co‐administration of XTANDI with strong CYP2C8 inhibitors
should be avoided if possible. If co‐administration of XTANDI
cannot be avoided, reduce the dose of XTANDI. Co‐administration of
XTANDI with strong or moderate CYP3A4 and CYP2C8 inducers may alter
the plasma exposure of XTANDI and should be avoided if
possible.
• Effect of XTANDI on Other Drugs ‐XTANDI is a strong CYP3A4
inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. 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.
About Astellas Pharma Inc.
Astellas Pharma Inc. is a pharmaceutical company dedicated to
improving the health of people around the world through provision
of innovative and reliable pharmaceuticals. The organization is
committed to being a global category leader in Oncology and
Urology, and has several oncology compounds in development in
addition to enzalutamide. For more information on Astellas Pharma
Inc., please visit our website at http://www.astellas.com/en.
About Medivation
Medivation, Inc. is a biopharmaceutical company focused on the
rapid development of novel therapies to treat serious diseases for
which there are limited treatment options. Medivation aims to
transform the treatment of these diseases and offer hope to
critically ill patients and their families. For more information,
please visit us at http://www.medivation.com.
About the Astellas/Medivation Collaboration
In October 2009, Medivation and
Astellas 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 advanced breast cancer. 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.
Forward Looking Statements
This press release contains forward-looking statements that are
made pursuant to the safe harbor provisions of the federal
securities laws, including statements regarding the potential
benefit of XTANDI in the indicated patient population. Any
statements contained in this press release that are not statements
of historical fact may be deemed to be forward-looking statements.
Forward-looking statements involve risks and uncertainties that
could cause Medivation's actual results to differ significantly
from those projected, including, without limitation, the risk that
unanticipated developments could delay or prevent the launch and
commercialization of XTANDI in the new indication, as well as other
risks detailed in Medivation's filings with the Securities and
Exchange Commission, including its quarterly report on Form 10-Q
for the quarter ended June 30, 2014,
filed on August 7, 2014 with the SEC.
You are cautioned not to place undue reliance on the
forward-looking statements, which speak only as of the date of this
release. Medivation disclaims any obligation or undertaking to
update or revise any forward-looking statements contained in this
press release.
