|Drug class||PARP inhibitor|
|Main uses||Breast cancer|
|Side effects||Tiredness, low red blood cells, nausea, low white blood cells, low platelets|
|By mouth (capsules)|
|Metabolism||Minimal metabolisation (<30%)|
|Elimination half-life||90 (±58) hrs|
|Excretion||69% in urine, 20% in feces|
|Chemical and physical data|
|Molar mass||380.359 g·mol−1|
|3D model (JSmol)|
Talazoparib, sold under the brand name Talzenna, is a medication used to treat metastatic or advanced breast cancer with BRCA mutation. It is generally used when other treatments are no longer working or suitable. It is taken by mouth.
Common side effects include tiredness, low red blood cells, nausea, low white blood cells, and low platelets. Other severe side effects may include myelodysplastic syndrome. Use during pregnancy may harm the baby. Lower doses may be used in people with kidney problems. It is a poly ADP ribose polymerase (PARP) inhibitor and works by blocking DNA repair.
Talazoparib was approved for medical use in the United States in 2018 and in Europe in 2019. In the United States a typical doses costs about 16,000 USD per month as of 2021. This amount in the United Kingdom costs the NHS about £5,000.
The most serious side effects in studies were related to the blood forming system and included anaemia (low red blood cell count), neutropenia (low neutrophil blood cell count) and thrombocytopenia (low platelet count). Serious forms of these conditions (grade 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.
Mechanism of action
Talazoparib acts as an inhibitor of poly ADP ribose polymerase (PARP) which aids in single strand DNA repair. Cells that have BRCA1/2 mutations are susceptible to the cytotoxic effects of PARP inhibitors because of an accumulation of DNA damage. Talazoparib is theorized to have a higher potency than olaparib due to the additional mechanism of action called PARP trapping. PARP trapping is the mechanism of action where the PARP molecule is trapped on the DNA, which interferes with the cells ability to replicate. Talazoparib is found to be ~100 fold more efficient in PARP trapping than olaparib. However, this increased potency may not translate directly to clinical effectiveness as many other factors must be considered.
Society and culture
Talazoparib was originally developed by BioMarin Pharmaceutical Inc. However, Medivation Inc. acquired all worldwide rights to talazoparib in August 2015, to expand their global oncology franchise. Medivation acquired talazoparib for $410 million with additional payments of up to $160 million in royalties and milestones. Under this agreement, Medivation assumed all financial responsibilities for the continued development, regulatory, and commercialization of talazoparib.
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