Enzalutamide Data Presented at ASCO GU Symposium

Enzalutamide Data Presented at ASCO GU Symposium 
Six Abstracts Presented Include Data from Phase II Study
Investigating XTANDI(R) (enzalutamide) Capsules in Hormone-Naive
Prostate Cancer 
SAN FRANCISCO, CA and TOKYO -- (Marketwire) -- 02/13/13 -- 
Medivation, Inc. (NASDAQ: MDVN) and Astellas Pharma Inc. (Tokyo:
4503) announced that data for enzalutamide, an oral androgen receptor
inhibitor, will be presented at the American Society of Clinical
Oncology (ASCO) 2013 Genitourinary (GU) Cancers Symposium in Orlando,
Florida.  
Title: Enzalutamide monotherapy: Phase 2 study results in
hormone-naive prostate cancer patients (Abstract #18) 
This phase 2 study assessed the efficacy and safety of enzalutamide
monotherapy (160 mg) in 67 patients who had never received hormone
therapy and presented with normal testosterone levels (≥230
ng/dL). The analysis showed: 


 
--  
Ninety-three percent of study participants experienced a ≥80%
    PSA decrease at week 25.
--  Median change in PSA was -99.6% (range -100% to -86.5%).
--  Serum testosterone increased by a mean of 114% at week 25 compared
    with baseline.
--  Frequent treatment-emergent adverse events (AEs) were mostly Grade 1
    or 2 and included gynecomastia (36%), fatigue (34%), nipple pain
    (19%), and hot flush (18%).
--  Endocrine level changes and the most common drug-related AEs were
    consistent with potent AR signaling inhibition.

  
Title: Enzalutamide in combination with docetaxel in men with
metastatic castration-resistant prostate cancer (mCRPC): preliminary
results from a phase 1 study (Abstract #63) 


 
--  A phase I study of enzalutamide given in combination with docetaxel in
    men with metastatic castration-resistant prostate cancer (mCRPC) who
    are on androgen deprivation therapy is currently ongoing. Preliminary
    data suggest that enzalutamide does not affect tolerability of
    docetaxel or have a clinically meaningful impact on docetaxel
    pharmacokinetics in this patient population.
--  Overall, enzalutamide was well tolerated with no patients
    discontinuing because of an enzalutamide-related adverse event.

  
Title: Impact of on-study corticosteroid use on efficacy and safety in
the phase 3 AFFIRM study of enzalutamide, an androgen receptor
inhibitor (Abstract #6) 


 
--  A post-hoc analysis of AFFIRM, a randomized, multinational,
    placebo-controlled phase 3 study among patients with mCRPC who had
    previously received docetaxel, showed that concomitant corticosteroid
    (CS) use was associated with reduced overall survival (median of 12.8
    months in the CS group vs. median not met in the no CS group) and
    higher rates of grade 3-4 adverse events (63.3% in the CS group vs.
    34.4% in the no CS group) in this population.

  
Title: Improved outcomes in elderly patients with metastatic
castration-resistant prostate cancer (mCRPC) treated with the
androgen receptor inhibitor enzalutamide: results from the Phase 3
AFFIRM trial (Abstract #16) 


 
--  A post-hoc analysis of the phase 3 AFFIRM study showed that outcomes
    in elderly (≥75 years) and younger ( Safety and tolerability
    findings were comparable between the two age groups.

  
Title: Enzalutamide improves health-related quality of life (HRQoL) in
men with metastatic castration-resistant prostate cancer (mCRPC)
following docetaxel-based therapy: results from the AFFIRM study
(Abstract #17) 


 
--  An analysis of patients enrolled in the enzalutamide phase 3 AFFIRM
    study showed that a greater percentage of patients on enzalutamide
    reported health-related quality of life (HRQoL) improvement compared
    to placebo (42.2% vs. 14.5%; p Both enzalutamide and placebo groups
    reported deterioration at some point during the study. However,
    compared with patients receiving placebo, patients receiving
    enzalutamide had a significantly prolonged time to HRQoL
    deterioration.

  
Title: Long-term responders to enzalutamide (ENZA) during the phase 3
AFFIRM trial: baseline characteristics and efficacy outcomes
(Abstract #20) 


 
--  In this post hoc analysis of AFFIRM data, 35% of patients remained on
    enzalutamide for ≥12 months and 22% for ≥18 months.

  
Compared with the all-enzalutamide group and the placebo group,
patients in the long-term exposure subgroup had somewhat less disease
burden at baseline, lower concomitant steroid use, and improved
efficacy outcomes consistently across multiple endpoints. 
About XTANDI(R)  
XTANDI(R) (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
(&#8805; 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 (&#8805;
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 no
t 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 CYP3A
4,
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 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 www.medivation.com.  
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 becoming a global category leader in
oncology, and has several oncology compounds in development in
addition to XTANDI. For more information on Astellas Pharma Inc.,
please visit our website at www.astellas.com/en 
Medivation Contacts:
Patrick Machado
Chief Business & Financial Officer
(415) 829-4101 
Anne Bowdidge
Senior Director, Investor Relations
(650) 218-6900 
Astellas Contacts:
Jenny Kite
Corporate Communications
(224) 204-5405 
Mike Beyer
Sam Brown, Inc (media for both companies)
(773) 463-4211 
 
 
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