In Preclinical Studies, ZEJULA-Induced Cytotoxicity Was Observed in Tumor Cell Lines With or Without Deficiencies in BRCA1/21

ZEJULA is an inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, PARP1 and PARP2, which play a role in DNA repair.1 In vitro studies suggest that ZEJULA's cytotoxic effects may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death.1

BRCA1/2, breast cancer susceptibility genes 1 and 2.

Preclinical studies suggest the activity of PARP inhibitors depends on tumor exposure and subsequent PARP1/2 inhibition.5

  • Tumor cells carrying a BRCA mutation have been shown to be significantly more sensitive to PARP inhibition than tumors that do not carry a BRCA mutation6
  • It is hypothesized that in tumors without a BRCA mutation, PARP inhibitors may need to achieve higher tumor concentrations for effect6

Pharmacologic Properties of ZEJULA

ZEJULA has high bioavailability and extensive tissue distribution, as well as a long half-life1

Highly bioavailable - Absolute bioavailability of ~73%, indicating minimal first-pass effect

Highly Bioavailable1

Absolute bioavailability of ≈73%, indicating minimal first-pass effect

Concentrates in tissue - Extensive tissue distribution, with a Vd/F of 1,220 L

Concentrates in Tissue1

Extensive tissue distribution, with a Vd/F of 1,220 L

Long half-life - Mean half-life of 36 h, allowing for once-daily dosing

Long Half-Life1

Mean half-life of 36 hours, allowing for once-daily dosing

BRCA, breast cancer susceptibility gene; PARP, poly(ADP-ribose) polymerase; Vd/F, apparent volume of distribution.

The Distinct Pharmacology of ZEJULA

Watch the following videos to learn more about the therapeutic rationale behind PARP inhibition and aspects of how ZEJULA behaves in the body.

References: 1. ZEJULA [package insert]. Waltham, MA: Tesaro, Inc; 2017. 2. Satoh MS, Lindahl T. Role of poly(ADP-ribose) formation in DNA repair. Nature. 1992;356:356-358. 3. Dale Rein I, Solberg Landsverk K, Micci F, Patzke S, Stokke T. Replication-induced DNA damage after PARP inhibition causes G2 delay, and cell line-dependent apoptosis, necrosis and multinucleation. Cell Cycle. 2015;14(20):3248-3260. 4. Data on file. TESARO, Inc. 5. Ricks TK, Chiu HJ, Ison G, et al. Successes and challenges of PARP inhibitors in cancer therapy. Front Oncol. 2015;5:222. 6. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917-921.

Efficacy summary


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Safety data


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Starting ZEJULA


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Study design


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