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Home Pfizer’s PARP Inhibitor Talzenna (Talazoparib) Receives Positive CHMP Opinion for gBRCAm/HER2-Negative Breast Cancer in the EU

Pfizer’s PARP Inhibitor Talzenna (Talazoparib) Receives Positive CHMP Opinion for gBRCAm/HER2-Negative Breast Cancer in the EU

Apr 27, 2019 17:12 CST Updated 17:12
Pfizer

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Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.


April 27, 2019/BioValleyBIOON/--U.S. Pharmaceutical GiantPfizer(Pfizer) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of the oral targeted anticancer drug Talzenna (talazoparib) as a monotherapy for patients with germlineBreast CancerTreatment of adult patients with germline BRCA1/2 (gBRCA) mutations and 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 were deemed inappropriate. Furthermore, patients with hormone receptor-positive (HR+) breast cancer should have previously received endocrine therapy, unless considered unsuitable for such therapy. The CHMP’s opinion will now be submitted to the European Commission (EC), which will take the CHMP’s opinion into account and render a final review decision within the next 2–3 months.

In the U.S. market, Talzenna was approved in October 2018FDAApproved, it became the fourth PARP inhibitor in the U.S. market; the three previously approved PARP inhibitors are:AstraZenecaof Lynparza, Clovis's Rubraca, Tesaro (which has beenGlaxoSmithKlineacquisition) of Zejula.

Talzenna is indicated for the treatment of adult patients with harmful or suspected harmful gBRCA mutations, HER2-negative locally advanced or metastatic breast cancer. The recommended dosage of Talzenna is 1 mg orally once daily, with or without food. At the time of Talzenna's approval,FDAalso approved Myriad Genetic Laboratories' companionDiagnosisThe BRACAnalysis CDx test kit is used to screen patients eligible for talazoparib treatment, specifically breast cancer patients with harmful or suspected harmful gBRCA mutations.

The CHMP’s recommendation to approve Talzenna is 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 germline BRCA (gBRCA) mutations and locally advanced (LA) or metastatic breast cancer (MBC). 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 (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 harmful or suspected harmful gBRCA mutations, had received no more than three prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease, and had previously been treated with an anthracycline and/or a taxane in the neoadjuvant, adjuvant, and/or metastatic settings (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 twofold increase in the proportion of patients achieving complete or partial response (62.6% vs. 27.2%, p<0.0001). Furthermore, the PFS benefit observed 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%).

Pfizer Global Product DevelopmentTumorDr. Chris Boshoff, Chief Development Officer, stated, “There is an urgent need for specifically designedHeredityNew effective drugs developed for patients with BRCA mutations, who are often diagnosed at a young ageDiagnosis...out, with limited treatment options for advanced disease. The results of the EMBRACA study provide evidence supporting the use of Talzenna in these patients, and we look forward to working with the European Commission to provide an alternative treatment option to chemotherapy.”

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 shown that talazoparib is highly effective and has a dual mechanism of action, inducing cell death by blocking PARP enzyme activity and trapping PARP at DNA damage sites.TumorCell Death. Currently, talazoparib is being evaluated for the treatment of gBRCAm breast cancer, early-stage triple-negative breast cancer (TNBC), and other types of cancer with DNA damage repair (DDR) deficiencies. (Bioon.com)