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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

VIEW EFFICACY RESULTS FOR HRD BRCAWT PATIENTS

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

DISCOVER EFFICACY OF ZEJULA IN PRIMA

Learn more about ZEJULA

Efficacy

See ZEJULA efficacy in PRIMA

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. Konstantinopoulos PA, et al. Cancer Discov. 2015;5:1137-54.
  5. Gonzales-Martin A, et al. N Engl J Med. 2019;381;2391-2402

Adverse events should be reported directly to the Health Products Regulatory Authority (HPRA) on their website: www.hpra.ie. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.

Zejula is a registered trademark of the GlaxoSmithKline group of companies.

September 2024 PM-IE-NRP-WCNT-220023