Only once-daily PARP inhibitor approved in Europe for hereditary breast cancer

NEW YORK, NY, USA I June 21, 2019 I Pfizer Inc. (NYSE:PFE) today announced that the European Commission approved TALZENNA® (talazoparib), an oral poly (ADP-ribose) polymerase (PARP) inhibitor, as monotherapy for the treatment of adult patients with germline breast cancer susceptibility gene (gBRCA)1/2-mutations, who have human epidermal growth factor receptor 2-negative (HER2-) locally advanced (LA) or metastatic breast cancer (MBC). Patients should have been previously treated with an anthracycline and/or a taxane in the (neo)adjuvant, locally advanced or metastatic setting unless patients were not suitable for these treatments. Patients with hormone receptor-positive (HR+) breast cancer should have been treated with a prior endocrine-based therapy, or be considered unsuitable for endocrine-based therapy.1 This approval follows the medicine’s approval by the U.S. Food and Drug Administration (FDA) in October 2018.

“Today’s approval of TALZENNA for certain patients with advanced-stage breast cancer and an inherited BRCA mutation is the latest example of our successful precision medicine approach to drug development,” said Andreas Penk, M.D., Regional President, Oncology International Developed Markets at Pfizer. “This important milestone builds on Pfizer’s decades-long legacy of developing therapies that improve outcomes for patients with breast cancer. We are thrilled that we can now offer these patients in Europe, who are often diagnosed at a younger age and have limited treatment options, an effective, once-daily, alternative treatment to chemotherapy.”

The European Commission’s approval of TALZENNA, which was acquired as part of Pfizer’s acquisition of Medivation, is based on results from the EMBRACA trial – the largest Phase 3 study of a PARP inhibitor in gBRCA-mutated, HER2- LA or MBC. The global trial evaluated once-daily TALZENNA compared to physician’s choice standard chemotherapy (capecitabine, eribulin, gemcitabine or vinorelbine) in patients with an inherited BRCA1/2 mutation in triple-negative or HR+/HER2- LA or MBC who may have received up to three prior cytotoxic chemotherapy regimens for their advanced disease. The primary endpoint was progression-free survival (PFS), as assessed by blinded independent central review (BICR).1,2

“In the EMBRACA trial, TALZENNA reduced the risk of disease progression by 46 percent and more than doubled the overall response rate compared to chemotherapy,” said Johannes Ettl, M.D., Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich in Germany and an investigator in the EMBRACA trial. “This improvement in outcomes for patients treated with TALZENNA reinforces the increasingly key role of genetic testing in treatment decision-making for patients with locally advanced or metastatic breast cancer.”

In the EMBRACA trial, TALZENNA significantly outperformed chemotherapy, extending median PFS to 8.6 months compared to 5.6 months for those treated with standard chemotherapy [95% CI: 7.2-9.3 vs. 4.2-6.7, respectively]. The superior PFS benefit with TALZENNA was observed across prespecified patient populations, including patients with triple-negative breast cancer, HR+/HER2- disease, with or without a history of CNS metastasis, and those who received prior cytotoxic chemotherapy regimens. Secondary endpoints from the EMBRACA trial included objective response rate (ORR), overall survival (OS) and safety. TALZENNA demonstrated an ORR of 62.6% (95% CI: 55.8-69.0), more than double that in the standard chemotherapy arm (27.2%) (95% CI: 19.3-36.3). OS is an event-driven endpoint and the data are not yet mature.1

Based on pooled data from patients who received 1 mg TALZENNA in clinical studies for solid tumors, the most common adverse reactions (≥ 25%) of patients receiving TALZENNA were fatigue (57.1%), anemia (49.6%), nausea (44.3%), neutropenia (30.2%), thrombocytopenia (29.6%) and headache (26.5%). Grade 3 or higher adverse reactions (≥ 10%) in patients treated with TALZENNA were anemia (35.2%), neutropenia (17.4%) and thrombocytopenia (16.8%).1

About EMBRACA

The pivotal, Phase 3, open-label, 2:1 randomized EMBRACA trial is the largest Phase 3 trial of a PARP inhibitor in gBRCA-mutated, HER2- LA or MBC. The trial evaluated TALZENNA (1 mg once daily) compared to physician’s choice chemotherapy (capecitabine, eribulin, gemcitabine or vinorelbine) in 431 patients with an inherited BRCA1/2 mutation and locally advanced or metastatic triple-negative or HR+/HER2- breast cancer who may have received up to three prior cytotoxic chemotherapy regimens. Of the patients enrolled, 190 were from European countries, such as Belgium, France, Germany, Ireland, Italy, Poland, Spain and the United Kingdom. The primary endpoint was PFS, as assessed by BICR. Safety, ORR and OS were key secondary endpoints.1,2

Primary results from the EMBRACA trial were published in the New England Journal of Medicine, simultaneous to the online publication of patient-reported outcomes data in Annals of Oncology in August 2018.2,3

For more information on the EMBRACA trial, go to www.clinicaltrials.gov.

About Germline (Inherited) BRCA-Mutated Breast Cancer

BRCA1 and BRCA2 are human genes that produce proteins involved in DNA repair. When either of these genes is altered or mutated, DNA repair may not progress correctly. This can lead to the development of certain types of cancer such as breast cancer.4 BRCA mutations can be hereditary (germline) or occur spontaneously (somatic).5 Together, germline BRCA1 and BRCA2 mutations account for about 25 to 30% of hereditary breast cancers and approximately 3 to 6% of all breast cancers.5,6,7,8,9

Epidemiologic studies indicate that individuals with gBRCA-mutated breast cancer are diagnosed in their 30s-40s, which is approximately 20 years younger than the overall breast cancer population.10,11

BRCA-mutated breast cancer is metastatic if the disease has spread beyond the breast or to other parts of the body, including the bones, liver, lung or brain.12 There is currently no cure for MBC, the most advanced stage (stage IV) of the disease. The goal of treatment is to delay or slow disease progression while maintaining quality of life.13,14

Current European and U.S. clinical guidelines recommend gBRCA testing to inform therapeutic considerations for HER2- LA or MBC patients.15,16

About talazoparib

Talazoparib is an inhibitor of PARP enzymes, which play a role in DNA repair. Preclinical studies suggest that talazoparib may work by blocking PARP enzyme activity and trapping PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death. Talazoparib anti-tumor activity also was observed in human patient-derived xenograft breast cancer tumor models that expressed mutated or wild-type BRCA1/2.1

In addition to gBRCA-mutated LA or MBC, talazoparib is being evaluated in several ongoing clinical trials in breast and other cancers, including early triple-negative breast cancer and prostate cancer, as well as other novel combinations with targeted therapies and studies with immunotherapy in various solid tumors.

Indication in the U.S.

TALZENNA® (talazoparib) is approved in the U.S. for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (gBRCA)‑mutated (gBRCAm) human epidermal growth factor receptor 2‑negative (HER2-), locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA.17

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of patients. Today, Pfizer Oncology has an industry-leading portfolio of 18 approved innovative cancer medicines and biosimilars across more than 20 indications, including breast, prostate, kidney, lung and hematology. Pfizer Oncology is striving to change the trajectory of cancer.

Pfizer Inc: Working together for a healthier world®

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube, and like us on Facebook at Facebook.com/Pfizer.

1 TALZENNA® (talazoparib). Summary of Product Characteristics.
2 Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018;379(8):753-763.
3 Ettl J, Quek R G W, Lee K-H, et al. Quality of life with talazoparib versus physician’s choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018: mdy257. doi:10.1093/annonc/mdy257.
4 National Cancer Institute. BRCA mutations: Cancer risk and genetic testing. https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet. Accessed September 10, 2018.
5 Kleibl Z, Kristensen VN. Women at high risk of breast cancer: molecular characteristics, clinical presentation and management. The Breast. 2016;28:136-144.
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9 Fasching PA, Hu C, Hart SN, et al. Cancer predisposition genes in metastatic breast cancer – association with metastatic pattern, prognosis, patient and tumor characteristics. Paper presented at: San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX.
10 Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA. 2017;317(23):2402–2416. doi:10.1001/jama.2017.7112.
11 Mavaddat N, Barrowdale D, Andrulis IL et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomarkers Prev 2012;21(1):134.
12 American Cancer Society. Treatment of invasive breast cancer, by stage. http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-treating-by-stage. Accessed September 20, 2018.
13 O’Shaughnessy J. Extending Survival with Chemotherapy in Metastatic Breast Cancer. The Oncologist. 2005;10:20-29.
14 Smith I. Goals of treatment for patients with metastatic breast cancer. Semin Oncol. 2006 Feb; 33(1 Suppl 2): S2-5.
15 Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol. 2018;29(8):1634-1657. doi:10.1093/annonc/mdy192.
16 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed May 8, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
17 TALZENNA® (talazoparib) Prescribing Information. New York. NY: Pfizer Inc: 2018.

SOURCE: Pfizer