Pfizer's PARP Inhibitor Talzenna Approved by EU as Fourth-in-Class Therapy for gBRCAm/HER2- Breast Cancer
Jun 22, 2019 09:59
CST Updated
09:59
Pfizer
Pharmaceutical R&D Developer
European Commission
The European Commission, abbreviated as the EU Commission, is a supranational body under the European Union. Within the EU political system, the European Commission primarily undertakes executive tasks, thus being roughly equivalent to the government in a national system. However, the European Commission has other functions as well. In particular, except for the few circumstances specified in the treaties, the European Commission is the only institution with legislative power in the EU legislative process.
June 22, 2019 /BioValleyBIOON/ -- U.S. pharmaceutical giantPfizer(Pfizer) recently announced that the European Commission (EC) has approved the targeted anticancer drug Talzenna (talazoparib), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, indicated as a monotherapy for the treatment of patients with germlineBreast CancerTreatment of adult patients with germline BRCA1/2 (gBRCA) mutations, HER2-negative locally advanced (LA) or metastatic breast cancer (MBC). It should be noted that patients should have previously received (neo)adjuvant, locally advanced, or metastatic treatment with anthracyclines and/or taxanes, unless such treatments are deemed inappropriate. Additionally, patients with hormone receptor-positive (HR+) breast cancer should have previously received endocrine therapy, unless considered unsuitable for endocrine therapy. Regarding dosage, the recommended dose of Talzenna is 1 mg orally once daily, with or without food.
It is worth mentioning that Talzenna is approved in Europe for the treatment ofGeneticsHereditary breast cancer (HBC) is the only once-daily oral PARP inhibitor, and it is also the fourth PARP inhibitor approved globally. In the United States, the drug was approved in October 2018.FDAApproved. The other three PARP inhibitors already approved for marketing are:AstraZenecaLynparza, Clovis’s Rubraca, Tesaro (which has beenGlaxoSmithKlineAcquisition) Zejula.
The approval of Talzenna was based on data from the pivotal, randomized Phase III clinical study EMBRACA (NCT01945775), which is the largest Phase III study conducted to date in patients with locally advanced (LA) or metastatic breast cancer (MBC) harboring germline BRCA (gBRCA) mutations. The study was conducted at 145 sites across 16 countries.Clinical TrialsA total of 431 patients with gBRCA1/2-mutated, triple-negative, or HR+/HER2− locally advanced or metastatic breast cancer (LA/MBC) were enrolled to evaluate the efficacy and safety of talazoparib versus physician’s choice of standard single-agent chemotherapy (initial chemotherapy [PCT]: capecitabine, eribulin, gemcitabine, or vinorelbine). In the study, patients were randomized in a 2:1 ratio to receive either talazoparib (1.0 mg once daily) or PCT. All patients had known deleterious or suspected deleterious gBRCA mutations, had received no more than three prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease, and had been treated with an anthracycline and/or a taxane in the neoadjuvant, adjuvant, and/or metastatic setting (unless contraindicated). The primary endpoint was progression-free survival (PFS), as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Data showed that, compared with the PCT treatment group, the talazoparib treatment group had a significantly prolonged progression-free survival (PFS) (median PFS: 8.6 months vs. 5.6 months; HR = 0.54 [95% CI: 0.41–0.71]; p < 0.0001), a significant 46% reduction in the risk of disease progression, and a doubled overall response rate (ORR: 62.6% vs. 27.2%; p < 0.0001). Furthermore, the PFS benefit associated with talazoparib treatment was consistent across all prespecified subgroups, including patients with a history of brain metastases, those who had previously received chemotherapy, patients with triple-negative breast cancer (TNBC), and patients with hormone receptor-positive (HR+) disease. In this study, the incidence of grade 3 or higher adverse events in the talazoparib treatment group was ≥10%.Adverse ReactionsIncludingAnemia(35%), neutropenia (17%), thrombocytopenia (17%).
PfizerTumorAndreas Penk, President of International Developed Markets, stated: “The European Union’s approval today of Talzenna for the treatment of patients with advanced breast cancer carrying germline BRCA mutations is the latest example of our success in developing precision medicines. This important milestone builds on Pfizer’s decades-long commitment to developing therapies that improve outcomes for patients with breast cancer.”HeredityPatients with BRCA mutations are often diagnosed at a young ageDiagnosis...limited treatment options for advanced-stage disease. The results of the EMBRACA study confirmed the robust efficacy of Talzenna in these patients, offering an effective, once-daily, chemotherapy-free treatment option.”
Talzenna was acquired by Pfizer through its acquisition of Medivation. The active pharmaceutical ingredient of this drug is talazoparib, a poly(ADP-ribose) polymerase (PARP) inhibitor. Preclinical studies have demonstrated that talazoparib is highly effective and exhibits a dual mechanism of action, inducing effects by blocking PARP enzyme activity and trapping PARP at sites of DNA damage.TumorCell Death. Currently, talazoparib is being evaluated for the treatment of gBRCAm breast cancer, early-stage TNBC, and other types of cancer with DNA damage repair (DDR) deficiencies. (Bioon.com)