Type of information: Granting of a Market Authorisation in the US
Product name: Talzenna®
Compound: talazoparib (BMN 673)
Therapeutic area: Cancer - Oncology
- enzyme inhibitor/poly ADP ribose polymerase PARP inhibitor/PARP inhibitor. Talazoparib is a potent and specific inhibitor of PARP 1 and 2 that is being developed by Medivation for the treatment of selected solid tumors. In pre-clinical studies, talazoparib has shown single-agent anti-tumor activity, as well as synergy in combination with lowered doses of DNA-damaging agents, due to its dual mechanisms of cytotoxicity, PARP trapping, and inhibition of PARP enzyme activity. Trapping of PARP on DNA impairs DNA replication resulting in tumor cell death.
Company: Pfizer (USA - NY)
- deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2?negative locally advanced or metastatic breast cancer
- • On October 16, 2018, the FDA approved talazoparib (Talzenna®), a poly (ADP-ribose) polymerase (PARP) inhibitor, for patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2?negative locally advanced or metastatic breast cancer. Patients must be selected for therapy based on an FDA-approved companion diagnostic for talazoparib.
- Approval was based on EMBRACA, an open?label trial randomizing 431 patients (2:1) with gBRCAm HER2?negative locally advanced or metastatic breast cancer to receive talazoparib (1 mg) or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine). All patients were required to have a known deleterious or suspected deleterious gBRCA mutation and must have received no more than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease. Patients were required to have received treatment with an anthracycline and/or a taxane (unless contraindicated) in the neoadjuvant, adjuvant, and/or metastatic treatment setting.
- The primary efficacy outcome was progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, as assessed by blinded independent central review. Estimated median PFS was 8.6 and 5.6 months in the talazoparib and chemotherapy arms, respectively (HR 0.54; 95% CI: 0.41, 0.71; p<0.0001).
- The prescribing information includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity. Most common (?20%) adverse reactions of any grade were fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, decreased appetite.
- FDA also approved the BRACAnalysis CDx test (Myriad Genetics) to identify patients with breast cancer with deleterious or suspected deleterious gBRCAm who are eligible for talazoparib. The effectiveness of the BRACAnalysis CDx test was based on the EMBRACA trial population for whom deleterious or suspected deleterious gBRCAm status was confirmed with either prospective or retrospective testing with BRACAnalysis CDx.
- The recommended talazoparib dose is 1 mg taken as a single oral daily dose, with or without food.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2018-10-16
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: