TOKYO and SAN FRANCISCO, April 2,
2015 /PRNewswire/ -- Astellas Pharma Inc. (TSE:
4503) and Medivation, Inc. (NASDAQ: MDVN) today announced
topline results from the Phase 2 STRIVE trial comparing
enzalutamide with bicalutamide in a study population of men with
non-metastatic or metastatic castration-resistant prostate cancer.
The study achieved its primary endpoint demonstrating a
statistically significant increase in progression-free survival
(PFS) for enzalutamide compared with bicalutamide (Hazard Ratio =
0.24; 95% Confidence Interval, 0.18-0.32; p<0.0001). Median PFS
was 19.4 months in the enzalutamide group compared with 5.7 months
in the bicalutamide group.
The median time on treatment in the STRIVE trial was 14.7 months
in the enzalutamide group versus 8.4 months in the bicalutamide
group. Serious adverse events were reported in 29.4% of
enzalutamide-treated patients and 28.3% of bicalutamide-treated
patients. Grade 3 or higher cardiac adverse events were
reported in 5.1% of enzalutamide-treated patients versus 4.0% of
bicalutamide-treated patients. One seizure was reported in the
trial in the enzalutamide-treated group and none in the
bicalutamide-treated group. The most common side effects noted more
frequently in the enzalutamide-treated versus bicalutamide-treated
patients included fatigue, back pain, hot flush, fall,
hypertension, dizziness, and decreased appetite, consistent with
the known safety profile of enzalutamide.
"These results demonstrate the potential for enzalutamide to
provide a longer duration of disease control compared with
bicalutamide in the studied patient population," said David
Penson, M.D., MPH, co-principal investigator of the STRIVE study,
Director of the Center for Surgical Quality and Outcomes Research
and Chair of the Department of Urologic Surgery of Vanderbilt University Medical Center.
The STRIVE study is the second of two head-to-head studies of
enzalutamide versus bicalutamide, the first of which was TERRAIN.
Additional results from the STRIVE trial, including the secondary
endpoints and safety data, will be submitted for presentation at
upcoming medical conferences.
About STRIVE
The Phase 2 STRIVE trial enrolled 396
castration-resistant prostate cancer patients in the United States. The trial randomized 257
patients with metastatic prostate cancer and 139 patients with
non-metastatic prostate cancer whose disease progressed despite
treatment with a luteinizing hormone-releasing hormone (LHRH)
analogue therapy or following surgical castration. The primary
endpoint of the trial was progression-free survival, defined as
time from randomization to radiographic (bone or soft tissue)
progression, PSA progression (defined by Prostate Cancer Working
Group 2 criteria), or death due to any cause, whichever occurs
first. The trial was designed to evaluate enzalutamide at a
dose of 160 mg taken once daily versus bicalutamide at a dose of 50
mg taken once daily, the approved dose in combination with a LHRH
analogue.
About TERRAIN
The Phase 2 TERRAIN trial enrolled 375
patients in North America and
Europe. The trial randomized
patients with metastatic prostate cancer whose disease progressed
despite treatment with a luteinizing hormone-releasing hormone
(LHRH) analogue therapy or following surgical castration. The
primary endpoint of the trial was progression-free survival,
defined as time from randomization to centrally confirmed
radiographic progression, skeletal related event, initiation of new
anti-neoplastic therapy or death, whichever occurs first. The trial
was designed to evaluate enzalutamide at a dose of 160 mg taken
once daily versus bicalutamide at a dose of 50 mg taken once daily,
the approved dose in combination with a LHRH analogue.
About XTANDI® (enzalutamide) capsules
XTANDI is approved by the U.S. Food and Drug Administration for the
treatment of patients with metastatic castration-resistant prostate
cancer (CRPC).
Enzalutamide Mechanism of Action
Enzalutamide is an androgen receptor inhibitor that acts on three
different steps in the androgen receptor signaling pathway.
Important Safety Information (from currently approved U.S.
prescribing 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-naive
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 readministering 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.
For Full Prescribing Information for XTANDI (enzalutamide)
capsules, please visit http://www.XtandiHCP.com/PI
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
www.astellas.com/en.
About Medivation, Inc.
Medivation, Inc. is a
biopharmaceutical company focused on the rapid development of
medically innovative 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 www.medivation.com.
About the Medivation/Astellas Collaboration
In
October 2009, Medivation (NASDAQ:
MDVN) 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 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.
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