SAN FRANCISCO, CA--(Marketwired - September 28, 2016) - Medivation, Inc. (NASDAQ: MDVN) today announced that new data from Company-sponsored and investigator-initiated clinical trials will be presented at the European Society for Medical Oncology (ESMO) 2016 Congress, being held October 7-11, in Copenhagen. Presentations include a pilot study of the company's investigational PARP inhibitor talazoparib in patients with BRCA-mutated breast cancer, and analyses of enzalutamide in the advanced prostate cancer setting, representing research advances in serious diseases for which there are limited options.
"We are excited to share data highlighting the clinical impact and potency of our potential best-in-class PARP inhibitor, talazoparib," said David Hung, M.D., founder, president and CEO of Medivation. "In addition, the breadth of enzalutamide data presentations shows our commitment to fully investigating its utility in patients with advanced prostate cancer."
Data presentations include:
Talazoparib: Investigational data demonstrating potential in BRCA-mutated breast cancer, for which there are no targeted treatment options:
- A pilot study of neoadjuvant talazoparib for early-stage breast cancer patients with a BRCA mutation [Abstract #153P; Saturday, October 8, 15:00 CEST]
Enzalutamide*: Updates on efficacy and safety, and additional analyses, in advanced prostate cancer:
- EMBARK: A Phase 3, randomized, efficacy and safety study of enzalutamide plus leuprolide, enzalutamide monotherapy, and placebo plus leuprolide in men with high-risk nonmetastatic prostate cancer progressing after definitive therapy [Abstract #770TiP; Sunday, October 9, 13:00 CEST]
- Prognostic factors in men with metastatic castration-resistant prostate cancer treated with enzalutamide or bicalutamide in TERRAIN [Abstract #759P; Sunday, October 9, 13:00 CEST]
- Efficacy and safety of enzalutamide plus androgen deprivation therapy vs placebo plus androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: the ongoing ARCHES trial [Abstract #767TiP; Sunday, October 9, 13:00 CEST]
- Efficacy and safety of enzalutamide vs placebo in chemotherapy-naïve patients with progressive metastatic castration-resistant prostate cancer following androgen deprivation therapy: an Asian multinational study [Abstract #749P; Sunday, October 9, 13:00 CEST]
* Enzalutamide is developed through a collaboration between Medivation and Astellas and commercialized under the brand name XTANDI®.
Talazoparib is a potent and specific inhibitor of PARP 1 and 2 that is being developed for the treatment of selected solid tumors. In pre-clinical studies, talazoparib has shown single-agent anti-tumor activity, as well as synergy in combination with lowered doses of DNA-damaging agents, due to its dual mechanisms of cytotoxicity, PARP trapping, and inhibition of PARP enzyme activity. Trapping of PARP on DNA impairs DNA replication resulting in tumor cell death. Talazoparib is in Phase III development for patients with locally advanced and/or metastatic breast cancer who harbor a germline BRCA1/2 mutation.
About XTANDI® (enzalutamide) capsules
XTANDI (enzalutamide) capsules are an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway within the tumor cell. In preclinical studies, enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors as well as inhibit androgen receptor nuclear translocation and interaction with DNA. The clinical significance of this MOA is unknown.
XTANDI is approved by the U.S. Food and Drug Administration for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).
Important Safety Information
Contraindications XTANDI is not indicated for women and is contraindicated in women who are or may become pregnant. XTANDI can cause fetal harm when administered to a pregnant woman.
Warnings and Precautions
Seizure In Study 1, conducted in patients with metastatic castration-resistant prostate cancer (CRPC) who previously received docetaxel, seizure occurred in 0.9% of XTANDI patients and 0% of placebo patients. In Study 2, conducted in patients with chemotherapy-naive metastatic CRPC, seizure occurred in 0.1% of XTANDI patients and 0.1% of placebo patients. There is no clinical trial experience re-administering XTANDI to patients who experienced a seizure, and limited safety data are available in patients with predisposing factors for seizure. Study 1 excluded the use of concomitant medications that may lower threshold; Study 2 permitted the use of these medications. Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity during which sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.
Posterior Reversible Encephalopathy Syndrome (PRES) In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.
The most common adverse reactions (≥ 10%) reported from two combined clinical studies that occurred more commonly (≥ 2% over placebo) in XTANDI patients were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo.
In Study 1, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In Study 2, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups.
- Lab Abnormalities: Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). Grade 1-4 thrombocytopenia occurred in 6% of XTANDI patients (0.3% Grade 3-4) and 5% of placebo patients (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of XTANDI patients (0.2% Grade 3-4) and 16% of placebo patients (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients (0.1% Grade 3-4) and 2% of placebo patients (no Grade 3-4).
- Infections: In Study 1, 1% of XTANDI patients compared to 0.3% of placebo patients died from infections or sepsis. In Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death.
- Falls (including fall-related injuries), occurred in 9% of XTANDI patients and 4% of placebo patients. 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.
- Hypertension occurred in 11% of XTANDI patients and 4% of placebo patients. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of all patients.
Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI. Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.
Effect of XTANDI on Other Drugs 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 http://www.astellas.us/docs/us/12A005-ENZ-WPI.pdf?v=1
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
About Medivation Inc.
Medivation, Inc. is a biopharmaceutical company focused on the development and commercialization of medically innovative 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 http://www.medivation.com.
Certain of the statements made in this press release, including those contained in Dr. Hung's quote, are forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements are subject to risks and uncertainties which may cause actual results to differ significantly from those expressed or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, results of the pilot study with talazoparib may not be reproduced or confirmed in subsequent controlled or pivotal clinical trials; Medivation's dependence on the efforts of and funding by Astellas for the development, manufacturing and commercialization of XTANDI; risks related to the timing, progress and results of Medivation's ongoing or planned clinical trials; the risk that adverse safety findings from ongoing clinical trials could result in the delay or discontinuation of Medivation's product development activities for XTANDI and/or talazoparib; changes in healthcare and pharmaceutical laws and regulations and reimbursement practices; and other risks detailed in Medivation's filings with the Securities and Exchange Commission, or SEC, including its quarterly report on Form 10-Q for the quarter ended June 30, 2016, which was filed on August 9, 2016. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this press release. Medivation disclaims any obligation or undertaking to update, supplement or revise any forward-looking statements contained in this press release.