Talazoparib

Talazoparib
Names
Trade namesTalzenna
Other namesBMN-673
IUPAC name
  • (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one
Clinical data
Drug classPARP inhibitor[1]
Main usesBreast cancer[1]
Side effectsTiredness, low red blood cells, nausea, low white blood cells, low platelets[2]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: D
    Routes of
    use    		By mouth (capsules)
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa618070
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • UK: POM (Prescription only) [3]
    • US: ℞-only
    • EU: Rx-only
    • In general: ℞ (Prescription only)
    Pharmacokinetics
    Protein binding74%
    MetabolismMinimal metabolisation (<30%)
    Elimination half-life90 (±58) hrs
    Excretion69% in urine, 20% in feces
    Chemical and physical data
    FormulaC19H14F2N6O
    Molar mass380.359 g·mol−1
    3D model (JSmol)
    SMILES
    • Cn1c(ncn1)[C@H]2c3c4c(cc(cc4N[C@@H]2c5ccc(cc5)F)F)c(=O)[nH]n3
    InChI
    • InChI=1S/C19H14F2N6O/c1-27-18(22-8-23-27)15-16(9-2-4-10(20)5-3-9)24-13-7-11(21)6-12-14(13)17(15)25-26-19(12)28/h2-8,15-16,24H,1H3,(H,26,28)/t15-,16-/m1/s1
    • Key:HWGQMRYQVZSGDQ-HZPDHXFCSA-N

    Talazoparib, sold under the brand name Talzenna, is a medication used to treat metastatic or advanced breast cancer with BRCA mutation.[1][2] It is generally used when other treatments are no longer working or suitable.[2] It is taken by mouth.[1]

    Common side effects include tiredness, low red blood cells, nausea, low white blood cells, and low platelets.[2] Other severe side effects may include myelodysplastic syndrome.[1] Use during pregnancy may harm the baby.[1] Lower doses may be used in people with kidney problems.[1] It is a poly ADP ribose polymerase (PARP) inhibitor and works by blocking DNA repair.[1][2]

    Talazoparib was approved for medical use in the United States in 2018 and in Europe in 2019.[1][2] In the United States a typical doses costs about 16,000 USD per month as of 2021.[4] This amount in the United Kingdom costs the NHS about £5,000.[5]

    Medical uses

    It is used for germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer.[6][7][8][2] It increases the time until disease worsens from 5.6 months to 8.6 months.[2]

    Dosage

    It is generally taken at 1 mg per day.[2] Lower doses may be used it side effects are too great.[2]

    Side effects

    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.[9]

    Interactions

    Combination with drugs that inhibit P-glycoprotein or BCRP may increase talazoparib concentrations in the body.[9]

    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.[10] 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.[11] However, this increased potency may not translate directly to clinical effectiveness as many other factors must be considered.[12][11]

    Society and culture

    Commercialization

    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.[13] 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.[13][14]

    Talazoparib is similar to the first in class PARP inhibitor, olaparib.[6][12]

    References

    1. 1 2 3 4 5 6 7 8 9 "Talazoparib Monograph for Professionals". Drugs.com. Archived from the original on 25 January 2021. Retrieved 13 August 2021.
    2. 1 2 3 4 5 6 7 8 9 10 "Talzenna EPAR". European Medicines Agency (EMA). 8 July 2019. Archived from the original on 19 May 2020. Retrieved 10 March 2020.
    3. ↑ "Talzenna 0.25 mg hard capsules - Summary of Product Characteristics (SmPC)". (emc). 1 June 2021. Archived from the original on 9 July 2021. Retrieved 9 July 2021.
    4. ↑ "Talzenna Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 15 January 2021. Retrieved 13 August 2021.
    5. ↑ BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 1065. ISBN 978-0-85711-369-6.
    6. 1 2 "FDA approves Lynparza to treat advanced ovarian cancer". U.S. Food and Drug Administration (FDA) (Press release). 19 December 2014. Archived from the original on 19 December 2014. Retrieved 9 July 2021.
    7. ↑ Pfizer Inc. "European Commission Approves TALZENNA (talazoparib) for Patients with Inherited (Germline) BRCA-Mutated Locally Advanced or Metastatic Breast Cancer". Archived from the original on 22 September 2020. Retrieved 14 March 2022.
    8. ↑ "Drug Approval Package: Talzenna (talazoparib)". U.S. Food and Drug Administration (FDA). 29 October 2018. Archived from the original on 30 October 2020. Retrieved 10 March 2020.
    9. 1 2 Talzenna FDA Professional Drug Information
    10. ↑ Medivation Inc. "Talazoparib". Archived from the original on 8 June 2017. Retrieved 9 July 2021.
    11. 1 2 Shen Y, Aoyagi-Scharber M, Wang B (June 2015). "Trapping Poly(ADP-Ribose) Polymerase". The Journal of Pharmacology and Experimental Therapeutics. 353 (3): 446–57. doi:10.1124/jpet.114.222448. PMID 25758918. S2CID 9810541.
    12. 1 2 Brown JS, Kaye SB, Yap TA (March 2016). "PARP inhibitors: the race is on". British Journal of Cancer. 114 (7): 713–5. doi:10.1038/bjc.2016.67. PMC 4984871. PMID 27022824.
    13. 1 2 Biomarin (24 August 2015). "Medivation to Expand Global Oncology Franchise With the Acquisition of All Worldwide Rights to Talazoparib (BMN 673), a Potent PARP Inhibitor, From BioMarin". Archived from the original on 5 February 2017. Retrieved 9 July 2021.
    14. ↑ Inman S (25 August 2015). "Medivation Acquires BioMarin's PARP Inhibitor Talazoparib". Archived from the original on 21 November 2016. Retrieved 9 July 2021.
    External sites:
    Identifiers:
    • "Talazoparib tosylate". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 29 August 2021. Retrieved 9 July 2021.
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