The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have agreed to review Pfizer’s application for talazoparib, a candidate for the treatment of metastatic breast cancer in patients with inherited BRCA mutations.
The request for the oral medicine’s approval to the FDA was accepted with priority review status, meaning talazoparib addresses an unmet patient need. A decision is expected by December.
Talazoparib is an investigational, once-daily PARP (poly ADP ribose polymerase) inhibitor, meaning it belongs to a drug class targeting DNA repair processes. The anti-cancer medicine has been shown in preclinical studies to be highly potent due to its dual mechanism of action, with potential to induce tumor cell death by blocking PARP enzyme activity and trapping PARP on sites of DNA damage.
In patients with BRCA mutations, the PARP enzyme is particularly important in repairing damage to DNA. When this enzyme is prevented from doing its job, cells — particularly fast-growing cancer cells — can accumulate enough DNA damage to kill them.
“Women with a hereditary BRCA mutation are typically diagnosed with breast cancer at a younger age than the overall breast cancer population and have limited treatment options when they develop advanced disease,” Mace Rothenberg, MD, chief development officer of oncology at Pfizer, said in a press release. “We are now one step closer to offering a potential alternative to chemotherapy for these patients.”
Talazoparib is currently being evaluated in patients with germline (inherited) BRCA-mutated (gBRCAm), HER2-negative and locally advanced or metastatic breast cancer in the Phase 3 EMBRACA trial (NCT01945775). The FDA submission was based on results from this trial, which concludes in December 2019.
The study met its primary endpoint already, demonstrating superior progression-free survival with talazoparib treatment — 1.0 mg capsules taken once daily — versus chemotherapy. This benefit was consistent across pre-specified patient subgroups, including patients with a history of brain metastases, patients previously treated with chemotherapy, patients with triple negative (a tumor not producing estrogen, progesterone, or HER2 receptors) and those with hormone receptor-positive breast cancer.
Severe adverse reactions that occurred with a frequency of at least 10 percent when administering talazoparib included anemia (35% of treated patients), low neutrophil — a type of white blood cell — counts (neutropenia, 17%) and low platelet levels (thrombocytopenia, 17%).
At that symposium, investigators showed that patients treated with talazoparib lived a median of 8.6 months without their disease worsening, a significantly longer time than the 5.6 months observed in patients given standard chemotherapy. This difference translates to a 46% reduction in the risk of cancer progression.
EMBRACA is the largest study to date examining a PARP inhibitor in patients with advanced or metastatic breast cancer and inherited BRCA mutations.