Medivation and Astellas Initiate Phase 2 Study of Enzalutamide in Advanced Breast Cancer That Is Estrogen or Progesterone

Medivation and Astellas Initiate Phase 2 Study of Enzalutamide in Advanced 
Breast Cancer That Is Estrogen or Progesterone Receptor
Positive and HER2 Normal 
SAN FRANCISCO, CA and NORTHBROOK, IL -- (Marketwired) -- 12/04/13 -- 
Medivation, Inc. (NASDAQ: MDVN) and Astellas Pharma US, Inc., a U.S.
subsidiary of Tokyo-based Astellas Pharma Inc. (TSE: 4503) announced
the initiation of a Phase 2 clinical trial evaluating the safety and
efficacy of enzalutamide in combination with exemestane in women with
advanced breast cancer that is estrogen receptor positive (ER+) or
progesterone receptor positive (PgR+) and human epidermal growth
factor receptor 2 (HER2) normal.  
"The androgen receptor is expressed in the majority of patients with
hormone receptor positive breast cancer," said Lynn Seely, M.D.,
chief medical officer of Medivation. "Exemestane is a commonly used
aromatase inhibitor in patients whose tumors express either the
estrogen or progesterone receptor. It is our hope that inhibiting
androgen receptor signaling with enzalutamide in combination with
exemestane will provide benefit beyond the inhibition of estrogen and
progesterone signaling in patients with advanced breast cancer." 
About the Phase 2 Study  
The Phase 2 study is a randomized, double-blind, placebo-controlled,
multicenter trial of enzalutamide in combination with exemestane
versus placebo plus exemestane in 240 postmenopausal women with
advanced breast cancer that is ER+ or PgR+ and HER2 normal that have
received no more than one prior chemotherapy and one prior hormonal
treatment for their advanced disease. The 240 patients will be
assessed in two parallel cohorts of 120 patients each. The first
cohort will enroll patients who have not previously received hormonal
treatment for advanced breast cancer. The second cohort will enroll
patients who have previously progressed following one hormonal
treatment for advanced disease. The primary endpoint of the trial is
progression-free survival in all patients and in the subset of
patients whose tumor expresses the androgen receptor. For more
information on this trial go to www.clinicaltrials.gov. 
About Enzalutamide  
Medivation and Astellas' clinical development plan for enzalutamide
in breast cancer also includes an ongoing Phase 2 trial evaluating
enzalutamide as a single agent for the treatment of advanced androgen
receptor positive, triple-negative breast cancer. The global study
initiated enrollment in June 2013.  
Enzalutamide is an androgen receptor inhibitor that acts on different
steps in the androgen receptor signaling pathway. Enzalutamide has
been shown to competitively inhibit androgen binding to androgen
receptors, and inhibit androgen receptor nuclear translocation and
interaction with DNA.  
About XTANDI(R) (enzalutamide) capsules 
  XTANDI was approved by the
U.S. Food and Drug Administration on August 31, 2012 and is indicated
for the treatment of patients with metastatic castration-resistant
prostate cancer (mCRPC) who have previously received docetaxel.  
Important Safety Information for XTANDI from the approved prescribing
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 for XTANDI (enzalutamide) capsules,
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 
  Astellas Pharma US, Inc., located in Northbrook,
Illinois, is a US 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 focused areas by combining
outstanding R&D and marketing capabilities. For more information
about Astellas Pharma US, Inc., please visit our website at
www.Astellas.us.  
Note Regarding Forward-Looking Statement - Medivation
  This press
release contains forward-looking statements, including statements
regarding the continued clinical development of enzalutamide and
potential future progress related thereto, the therapeutic potential
of enzalutamide among patients advanced breast cancer that is ER+ or
PgR+ and HER2 normal, our strategy, and the continued effectiveness
of, and continuing collaborative activities and benefits under,
Medivation's collaboration agreement with Astellas, which are made
pursuant to the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995. 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, risks related to the timing and results of Medivation's
clinical trials, including the risk that adverse clinical trial
results could alone or together with other factors result in the
delay or discontinuation of some or all of Medivation's product
development activities, the risk that positive results seen in our
clinical trials may not be predictive of the results of our ongoing
or planned clinical trials, difficulties or delays in enrolling and
retaining patients in Medivation's clinical trials, Medivation's
dependence on the efforts of and funding by Astellas for the
development of enzalutamide, the achievement of development,
regulatory and commercial milestones under Medivation's collaboration
agreement with Astellas, the manufacturing of Medivation's product
candidates, the industry and competitive market, the adequacy of
Medivation's financial resources, unanticipated expenditures or
liabilities, Medivation's outstanding convertible senior notes,
intellectual property matters, and 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
September 30, 2013, filed with the SEC on November 12, 2013. 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) 205-5405 
Mike Beyer
Sam Brown, Inc (media for both companies)
(773) 463-4211  
 
 
Press spacebar to pause and continue. Press esc to stop.