ZEJULA (niraparib) mechanism of action

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.1

ZEJULA is a PARP inhibitor, so it works by inhibiting the repair of damaged DNA and inducing cell death.2

How ZEJULA works

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

Figure adapted from Konecny et al. 2016.3

Homologous recombination deficient (HRd) cells are sensitive to PARP inhibitors

Cells defective in the homologous recombination (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.1

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

DNA and molecules icon

Biomarkers in ovarian cancer

HRd is an important therapeutic target in ovarian cancer4,5

A diagram showing the biomarker statuses in ovarian cancer

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

~25% are BRCAmut4,5

ZEJULA as first-line maintenance therapy for platinum-responsive advanced ovarian cancer patients extends PFS, regardless of biomarker status2,5,6

ZEJULA is indicated:2

  • 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.

Footnotes

BRCA, breast cancer susceptibility gene; BRCAmut, BRCA mutation; BRCAwt, BRCA wild-type; DNA, deoxyribonucleic acid; HR, homologous recombination; HRd, homologous recombination deficient; HRp, homologous recombination proficient; MoA, mechanism of action; PARP, poly(ADP-ribose) polymerase; PFS, progression-free survival. ; QoL, quality of life

References

  1. Rose M, et al. Front Cell Dev Biol. 2020;8(564601):1-22.
  2. ZEJULA Summary of Product Characteristics.
  3. Konecny GE, Kristeleit RS. Br J Cancer.2016;115(10):1157-1173.
  4. Miller RE, et al. Annals on Oncology. 2020;31(12):1606-1622.
  5. Konstantinopoulos PA, et al. Cancer Discov. 2015;5:1137-54.
  6. Gonzales-Martin A, et al. N Engl J Med. 2019;381;2391-2402

Adverse events should be reported.
Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ or search for MHRA Yellowcard in the Google Play or Apple App store.

Adverse events should also be reported to GlaxoSmithKline on 0800 221 441.

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March 2022 | PM-GB-NRP-WCNT-210021 (V1.0)

February 2022 | PM-GB-NRP-WCNT-210016 v1.0