Medivation and Astellas Announce New Data From XTANDI(R) (enzalutamide) Pivotal Study

Sun Sep 30, 2012 7:00am EDT

* Reuters is not responsible for the content in this press release.

  SAN FRANCISCO, CA and TOKYO, Sep 30 (Marketwire) -- 
Medivation Inc. (NASDAQ: MDVN) and Astellas Pharma Inc. (TSE: 4503)
announced that new data for enzalutamide (XTANDI(R) capsules), an oral
androgen receptor inhibitor, were presented today at the 2012 European
Society of Medical Oncology (ESMO) Annual Meeting in Vienna, Austria. The
data from the randomized, global, placebo-controlled phase 3 AFFIRM study
highlight the effect of enzalutamide on pain-related secondary endpoints
and a post hoc analysis of the survival impact of baseline corticosteroid
use among men with advanced prostate cancer.

    "Findings from the corticosteroid analysis showed that patients in both
the enzalutamide and the placebo groups taking glucocorticoids had an
inferior survival compared to those who did not take glucocorticoids,"
said Dr. Howard I. Scher, chief, Genitourinary Oncology Service, Sidney
Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering
Cancer Center, and co-principal investigator for AFFIRM. "Patients on
enzalutamide fared better than those on placebo whether or not they were
taking corticosteroids, which confirmed the survival benefit associated
with enzalutamide while suggesting the impact of corticosteroids on
outcomes be explored further."

    "Additionally, the pain-related data presented today provide additional
information to help those of us who treat prostate cancer on a daily
basis to assess the benefits of enzalutamide for the individual
patients," Scher said.

    Title: Association of baseline corticosteroid with outcomes in a
multivariate analysis of the Phase 3 AFFIRM study of enzalutamide (ENZA),
an androgen receptor signaling inhibitor (Abstract # 899PD) 

    Dr. Scher presented results from a post hoc AFFIRM analysis evaluating
the impact of baseline corticosteroid use on efficacy outcomes. 

    Approximately 30 percent of patients in both the AFFIRM enzalutamide and
placebo arms were receiving corticosteroids at baseline. The analyses
presented showed:


--  Baseline corticosteroid use was associated with reduced survival
    regardless of study treatment (i.e., enzalutamide or placebo).
--  Enzalutamide was consistently superior to placebo on overall survival
    (OS), radiographic progression-free survival (rPFS) and time to PSA
    progression (TTPP) regardless of baseline corticosteroid use.
--  After adjustment for the effects of other prognostic factors, the
    analysis demonstrated baseline corticosteroid use was still associated
    with poorer overall survival outcome.

    

Title: Impact of enzalutamide, an androgen receptor signaling
inhibitor, on time to first skeletal related event (SRE) and pain in the
phase 3 AFFIRM study (Abstract #8960)

    Karim Fizazi, MD, PhD, head of the Department of Cancer Medicine at the
Institut Gustave Roussy, Villejuif, France, presented data on AFFIRM
pain-related quality-of-life endpoints which demonstrate: 


--  Pain reduction assessed by patient diaries was achieved by 45 percent
    of enzalutamide patients vs. 7 percent of placebo patients (p=0.0079).
--  Patients taking enzalutamide demonstrated less pain progression and
    improved median time to pain progression as compared to those taking
    placebo.
--  Enzalutamide-treated patients also experienced improvements over
    placebo in mean reduction in pain severity, and pain interference with
    daily activity.
--  Enzalutamide-treated participants also experienced delayed time to
    first skeletal-related event (SRE): 16.7 months as compared to 13.3
    months for those on placebo (HR=0.69 p=0.0001), representing a 31
    percent reduction in SRE risk.

    

In the Phase 3 AFFIRM trial common side effects observed more
frequently in XTANDI as compared with placebo-treated patients included
fatigue, diarrhea and hot flush. Seizure was reported in < 1% of
enzalutamide-treated patients. Serious adverse events, adverse events
causing patients to stop treatment, and adverse events causing death all
were lower in the enzalutamide group than in the placebo group. 

    About XTANDI 

    XTANDI 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 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.

    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. 

    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 for XTANDI 
 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. 

    Warning and Precautions - In the randomized phase 3 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. 

    Drug Interactions - Enzalutamide is a strong CYP3A4 inducer and a
moderate CYP2C9 and CYP2C19 inducer in humans. 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. 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 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. 

    This press release contains forward-looking statements that are made
pursuant to the safe harbor provisions of the federal securities laws,
including statements regarding therapeutic potential of XTANDI. 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 interfere with the commercialization of XTANDI, 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, 2012, filed on August 9, 2012 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.

    

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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