Astellas Highlights Progress to Advance Care of Patients with Genitourinary Cancers at ASCO-GU Annual Meeting<4503.T>

Wed Feb 13, 2013 8:00am EST

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NORTHBROOK, Ill.,  Feb. 13, 2013  /PRNewswire/ -- Astellas Pharma US, Inc., a
U.S. subsidiary of  Tokyo-based Astellas Pharma Inc. (Tokyo: 4503), today
announced that more than 10 abstracts from Astellas oncology pipeline agents and
marketed products will be presented at the 2013 American Society of Clinical
Oncology Genitourinary Cancers Symposium (ASCO-GU), to be held  February 14-16 
in  Orlando, Florida.  

"We're committed to delivering new treatment options for patients with GU
cancers," said  Mark Reisenauer, vice president, Astellas Oncology. "The data to
be presented at ASCO GU further illustrates the potential role our products can
play."

Key presentations to be made at ASCO-GU include:

Enzalutamide  

Data from a 25-week, open label, single-arm phase 2 study highlighting the
effect of enzalutamide on prostate-specific antigen (PSA) response in men with
hormone-naive prostate cancer will be presented. Five additional abstracts will
highlight outcomes from a phase 1 study of enzalutamide in combination with
docetaxel chemotherapy, as well as additional findings from the randomized,
global, placebo-controlled phase 3 AFFIRM study of enzalutamide in men with
metastatic castration resistant prostate cancer. XTANDI was approved by the FDA
on  August 31, 2012  for the treatment of patients with metastatic
castration-resistant prostate cancer who have previously received docetaxel
(chemotherapy). A Marketing Authorization Application for XTANDI is currently
under review by the European Medicines Agency (EMA).

Tivozanib

Additional secondary analysis results from the Phase 3 TIVO-1 (tivozanib versus
sorafenib in 1st line advanced RCC) trial will be presented.  Reported data will
include overall survival (OS) results for metastatic renal cell carcinoma (mRCC)
patients who received tivozanib versus patients who received sorafenib in the
TIVO-1 study.  Additionally, four posters with tivozanib data regarding the
safety and efficacy profile of tivozanib will also be presented at the meeting.
A new drug application (NDA) for tivozanib, an investigational agent,  is
currently under review by the FDA for the treatment of patients with advanced
renal cell carcinoma.

"We applaud companies such as Astellas that are committed to developing
medicines for difficult-to-treat cancers," said  Helen Miller, LCSW, CancerCare
CEO. "We share their commitment to put cancer patients first."

About Astellas  

Astellas Pharma US, Inc., located in  Northbrook, Illinois, is a U.S. affiliate
of  Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company
dedicated to improving the health of people around the world through the
provision of innovative and reliable pharmaceutical products. The organization
is committed to becoming a global category leader in oncology, and has several
oncology products on the market and compounds in development. Astellas is proud
to be an award recipient of the CEO Gold Standard Accreditation from the CEO
Roundtable on Cancer. For more information on Astellas Pharma Inc., please visit
our website at  www.astellas.us.

About XTANDI®   

XTANDI (enzalutamide) capsules is an oral, once-daily androgen receptor
inhibitor. XTANDI was approved by the FDA on  August 31, 2012  for the treatment
of metastatic castration-resistant prostate cancer for patients who have
previously received docetaxel (chemotherapy). A Marketing Authorization
Application for XTANDI is currently under review by the European Medicines
Agency (EMA).  

The efficacy and safety of XTANDI were assessed in the randomized,
placebo-controlled, global phase 3 AFFIRM clinical trial. A total of 1,199
patients with mCRPC who had previously received docetaxel were randomized 2:1 to
receive either XTANDI orally at a dose of 160 mg once daily (N = 800) or placebo
(N = 399). Patients with a history of seizure, taking medications known to
decrease the seizure threshold, or with other risk factors for seizure were
excluded from the clinical trial. The primary endpoint of the trial was OS.

XTANDI-treated patients had a statistically-significant improvement in median OS
compared to the placebo group: 18.4 months in the XTANDI group versus 13.6
months in the placebo group (P < 0.0001). XTANDI provided a 37% reduction in
risk of death compared to placebo (hazard ratio = 0.631). Seizure occurred in
0.9% of patients on XTANDI and 0% of the placebo-treated patients. The most
common adverse reactions (≥ 5%) are asthenia/fatigue, back pain, diarrhea,
arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper
respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory
infection, spinal cord compression and cauda equina syndrome, hematuria,
paresthesia, anxiety, and hypertension. Grade 3 and higher adverse reactions
were reported among 47% of XTANDI-treated patients and 53% of placebo-treated
patients.  

The recommended dose of XTANDI is 160 mg (four 40 mg capsules) administered
orally once daily. XTANDI can be taken with or without food and does not require
concomitant steroid (e.g., prednisone) use. In the phase 3 clinical trial, 48%
of XTANDI patients and 46% of patients in the placebo arm were treated with
glucocorticoids.

XTANDI Mechanism of Action  

XTANDI (enzalutamide) is an androgen receptor inhibitor that acts on different
steps in the androgen receptor signaling pathway. XTANDI has been shown to
competitively inhibit androgen binding to androgen receptors, inhibit androgen
receptor nuclear translocation and interaction with DNA. A major metabolite,
N-desmethyl enzalutamide, exhibited similar  in vitro  activity to XTANDI.
XTANDI decreased proliferation and induced cell death of prostate cancer cells 
in vitro, and decreased tumor volume in a mouse prostate cancer xenograft model.
 

Important Safety Information  

Contraindications-  XTANDI can cause fetal harm when administered to a pregnant
woman based on its mechanism of action. XTANDI is not indicated for use in
women. XTANDI is contraindicated in women who are or may become pregnant.  

Warnings and Precautions- In the randomized clinical trial, seizure occurred in
0.9% of patients on XTANDI. No patients on the placebo arm experienced seizure.
Patients experiencing a seizure were permanently discontinued from therapy. All
seizures resolved. Patients with a history of seizure, taking medications known
to decrease the seizure threshold, or with other risk factors for seizure were
excluded from the clinical trial. Because of the risk of seizure associated with
XTANDI use, patients should be advised of the risk of engaging in any activity
where sudden loss of consciousness could cause serious harm to themselves or
others.  

Adverse Reactions-  The most common adverse drug reactions (≥ 5%) reported in
patients receiving XTANDI in the randomized clinical trial were
asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema,
musculoskeletal pain, headache, upper respiratory infection, muscular weakness,
dizziness, insomnia, lower respiratory infection, spinal cord compression and
cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension. Grade
1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and in 6% on
placebo (no Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of
XTANDI patients and 2% on placebo. One percent of XTANDI patients compared to
0.3% on placebo died from infections or sepsis. Falls or injuries related to
falls occurred in 4.6% of XTANDI patients vs 1.3% on 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. Grade 1 or 2 hallucinations occurred in 1.6% of XTANDI
patients and 0.3% on placebo, with the majority on opioid-containing medications
at the time of the event.  

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
can 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, please visit  www.XtandiHCP.com.

About Tivozanib

Tivozanib is a potent, selective and long half-life inhibitor of all three
vascular endothelial growth factor (VEGF) receptors that is designed to optimize
VEGF blockade while minimizing off-target toxicities. Tivozanib is an oral,
once-daily, investigational tyrosine kinase inhibitor for which positive results
from a Phase 3 clinical study in advanced RCC have been reported, and is being
evaluated in other tumors.

SOURCE  Astellas Pharma US, Inc.


Jenny Kite, Astellas, +1-224-205-5405, jenny.kite@astellas.com

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