SAN FRANCISCO, CA--(Marketwired - April 17, 2016) - Medivation, Inc. (NASDAQ: MDVN) today announced that Phase I data from its investigational agent talazoparib, a highly-potent PARP inhibitor, was presented at the American Association for Cancer Research (AACR) Annual Meeting 2016 in New Orleans by the study's lead investigator Zev A. Wainberg, M.D., Associate Professor of Medicine at the University of California Los Angeles (UCLA) and Co-Director of the UCLA GI Oncology Program, during a Clinical Trials Mini-Symposium. The primary objective of the study was to determine the maximum tolerated dose (MTD) of talazoparib in combination with either low-dose temozolomide or low-dose irinotecan in heavily pretreated patients with advanced malignancies.
The data from the 40 patient trial demonstrated that combination treatment with talazoparib and low-dose chemotherapy resulted in stable disease or an objective response in 23 of 40 heavily pretreated patients with a variety of advanced cancers (clinical benefit rate of 58%). Most notably, objective responses were seen in four of seven (57%) heavily pre-treated non-BRCA-mutated ovarian cancer patients when talazoparib was used in combination with either low-dose temozolomide or low-dose irinotecan. Six of seven individuals (86%) with non-BRCA ovarian cancer had clinical benefit (four partial responses and two stable disease) and had a reduction in CA 125 levels by 50% or greater.
Importantly, the overall study demonstrated responses to combination talazoparib/low-dose chemotherapy in patients with multiple tumor types in which specific deleterious mutations in certain DNA repair genes extended beyond BRCA deficiency, including one patient who did not meet the criteria of having homologous recombination deficiency (HRD). These effects may be mediated through PARP inhibition, as well as enhanced PARP trapping, which interferes with the tumor cell's ability to replicate DNA by locking PARP molecules onto the DNA strand.
"In non-clinical studies, talazoparib has been shown to have high potency specifically against PARP 1 and 2, and antitumor effects in various solid tumors. With these new results, we now have evidence in humans that suggests talazoparib in combination with low-dose chemotherapy is active in tumors with defects in DNA repair beyond BRCA deficiency, and possibly in patients without evidence of HRD. We feel these data are consistent with talazoparib's potent PARP trapping ability, which we believe makes talazoparib a unique and exciting product candidate with the potential to be used in combination with DNA damaging therapies across a wide variety of tumor types," said David Hung M.D., Founder, President and Chief Executive Officer of Medivation. "With more than half of the ovarian cancer patients demonstrating an objective response, particularly in a heavily pre-treated patient population with advanced disease, these findings are encouraging and support further evaluation of the safety and efficacy of talazoparib."
Talazoparib currently is in Phase III development for patients with locally advanced and/or metastatic breast cancer who harbor a germline BRCA1/2 mutation. It is also being studied in several investigator-sponsored trials across multiple tumor types.
The Phase I investigator-sponsored study evaluated escalating doses of talazoparib ( ‰¥ 0.5 mg given orally once daily) with either temozolomide ( ‰¥ 25 mg/m2 given orally on days 1-5; Arm A) or irinotecan ( ‰¥ 25 mg/m2 given by intravenous infusion every two weeks; Arm B) every 28 days in patients with advanced malignancies. Study participants ranged in age from 21 to 77 years (median: 57 years) and had received one to 15 prior chemotherapy regimens (median: 6). The primary endpoint of the study was the determination of the MTD. Secondary endpoints included pharmacokinetics, tumor response and biomarkers.
A total of 40 patients received escalating doses of talazoparib (0.5-1.0 mg) and either temozolomide or irinotecan (18 patients in Arm A and 22 in Arm B). Results showed the MTD for talazoparib was 1.0 mg. and 37.5 mg/m2 for either temozolomide or irinotecan when combined with 1.0 mg talazoparib. Partial responses were seen in four of seven (57%) germline BRCA wild type ovarian cancer patients who were platinum-resistant. Additional responses were seen in one patient each with Ewing's Sarcoma, cervical adenocarcinoma, small cell lung cancer, and triple negative breast cancer. An association was observed between response and the presence of deleterious somatic mutations in DNA repair genes (PALB2 and RAD51D) distinct from BRCA mutations.
The most common grade 3/4 adverse events ( ‰¥ 5%) observed in patients treated with talazoparib plus temozolomide were neutropenia (28%), anemia (33%), and thrombocytopenia (33%). Among those treated with talazoparib plus irinotecan, the most common adverse events were thrombocytopenia (13%), anemia (27%) and neutropenia (31%). No significant pharmacokinetic interactions were observed between talazoparib and either temozolomide or irinotecan.
About Talazoparib
Talazoparib is a potent and specific inhibitor of PARP 1 and 2
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.
Forward-Looking Statements
This press release contains forward-looking statements, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and 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 risks that the results and responses demonstrated in this Phase I clinical trial and the other correlations and associations observed herein may not be reproduced or confirmed in subsequent pivotal or controlled clinical trials; further investigation of talazoparib in combination with DNA damaging therapies may not occur; the risk that Medivation may observe unfavorable results or unexpected adverse events from other clinical trials involving talazoparib which could cause delay or discontinuation of Medivation's development of talazoparib; and other risks detailed in Medivation's filings with the Securities and Exchange Commission, or SEC, including its annual report on Form 10-K for the year ended December 31, 2015, which was filed on February 26, 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.
Contacts:
Investors
Anne Bowdidge
(650) 218-6900
Media
Ryan Flinn
Brewlife
On behalf of Medivation
(415) 946-1059
