Talazoparib (unofficial Chinese translation: talazoparib/talazoparib), brand name Talzenna, is an oral poly ADP ribose polymerase (PARP) inhibitor developed by Pfizer for the treatment of advanced breast cancer with germline BRCA mutations.
Talazoparib is similar to the comparable PARP inhibitor Olaparib. It was approved in the United States in October 2018 and in the European Union in June 2019 for the treatment of locally advanced or metastatic breast cancer with germline BRCA mutations and HER2 negativity.
The most serious side effects in the study were related to the blood-forming system and included anemia (low red blood cell count), neutropenia (low neutrophil count) and thrombocytopenia (low platelet count). Severe forms of these conditions (grades 3 to 4) occurred in 39%, 21% and 15% of patients, respectively. Other adverse effects, such as headache, nausea, hair loss and fatigue were mostly mild.
Combination with drugs that inhibit P-glycoprotein or BCRP may increase the concentration of Talazoparib in the body.
Talazoparib acts as an inhibitor of poly ADP ribose polymerase (PARP) and contributes to single-stranded DNA repair. Cells with BRCA1/2 mutations are susceptible to the cytotoxic effects of PARP inhibitors due to accumulated DNA damage. It is hypothesized that Talazoparib is more potent than olaparib due to an additional mechanism of action called PARP trapping, a mechanism of action in which PARP molecules are trapped in DNA and interfere with the cell’s ability to replicate. talazoparib was found to be approximately 100-fold more efficient than olaparib at trapping PARP . However, this increase in potency may not translate directly into clinical effects due to the many other factors that must be considered.
Talazoparib was originally developed by BioMarin Pharmaceuticals, Inc. However, Medivation acquired all global rights to talazoparib in August 2015 to expand its global oncology franchise. medivation acquired talazoparib for $410 million and paid up to an additional $160 million in royalties and milestones. Under this agreement, Medivation assumed all financial responsibility for the continued development, stewardship and commercialization of talazoparib. On September 28, 2016, Pfizer completed the acquisition of Medivation.