SAN FRANCISCO, CA and NORTHBROOK, IL, Dec 04, 2013 (Marketwired via COMTEX) -- Medivation, Inc.MDVN -0.42% and Astellas Pharma US, Inc., a U.S. subsidiary of Tokyo-based Astellas Pharma Inc. 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.
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.