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How ZEJULA (Niraparib) works

ZEJULA works by inhibiting PARP to prevent the repair of damaged DNA1

Poly (ADP) ribose polymerase (PARP) is a protein that plays a fundamental role in the detection and repair of DNA damage in cells, including damage induced by chemotherapy.2

ZEJULA is a PARP inhibitor, so it works by inhibiting the repair of damaged DNA and inducing cell death.1

How does ZEJULA work?

Diagram showing the mechanism of action of a PARP inhibitor in the DNA repair pathway

Figure adapted from Konecny et al. 20163

DNA and molecules icon

Why are PARP inhibitors especially effective in HRd patients?

Cells defective in the HR pathway are known as HRd cells. They rely heavily on other repair proteins, such as PARP, to survive.4 PARP plays a fundamental part in the detection and repair of DNA damage; therefore, inhibiting PARP in HRd cells results in two defective DNA repair mechanisms and, ultimately, cell death.2

In HRp cells, damaged DNA may be repaired via the HR pathway.4

What proportion of patients are HRD?
What about BRCAmut?

~50% of high-grade serous ovarian tumours are HRd4,5
~25% are BRCAmut4,5

  • BRCA1 and BRCA2 produce proteins essential for repairing DNA damage via the HR pathway5
  • Mutations in BRCA1/2 correlate with an HRd status5

Biomarkers in ovarian cancer

A diagram showing the biomarker statuses in ovarian cancer

WHAT ABOUT ZEJULA EFFICACY?

Find out more

MoA resources

ZEJULA is indicated

  • as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.
  • as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Abbreviations

ADP, adenosine diphosphate; BRCA, breast cancer susceptibility gene; BRCAmut, BRCA mutation; BRCAwt, BRCA wild-type; DNA, deoxyribonucleic acid; FIGO, Federation of Gynaecology and Obstetrics; HR, homologous recombination; HRD (homologous recombination deficiency) and HRd (homologous recombination deficient); MoA, mechanism of action; PARP, poly(ADP-ribose) polymerase; QoL, quality of life.

References

  1. ZEJULA (niraparib). Summary of product characteristics.
  2. Rose M, et al. Front Cell Dev Biol. 2020;8(564601):1-22
  3. Konecny G, Kristeleit R. Br J Cancer. 2016;115(10):1157-1173.
  4. Miller R, et al. Annals on Oncology. 2020;31(12):1606-1622.
  5. Konstantinopoulos P, et al. Cancer Discov. 2015;5:1137-54.

Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk (UK) or search for MHRA Yellow Card in the Google Play or Apple App store. Adverse events should also be reported to GSK Limited on 0800 221 441 or by email at uksafety@gsk.com.

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June 2023 | PM-GB-NRP-WCNT-220018 (V1.0)