Olaparib: First Global Approval

Abstract

Olaparib (Lynparza™) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor being developed by AstraZeneca for the treatment of solid tumours. The primary indication that olaparib is being developed for is BRCA mutation-positive ovarian cancer. A capsule formulation of the drug has received approval for use in this setting in the EU and USA, and a tablet formulation is in global phase III trials (including in the USA, EU, Australia, Brazil, Canada, China, Israel, Japan, Russia and South Korea). In addition, phase III trials in breast, gastric and pancreatic cancer are underway/planned, and phase I/II investigation is being conducted in other malignancies, including prostate cancer, non-small cell lung cancer, Ewing's sarcoma and advanced cancer. This article summarizes the milestones in the development of olaparib leading to this first approval for ovarian cancer.

Olaparib protects cardiomyocytes against oxidative stress and improves graft contractility during the early phase after heart transplantation in rats

“…Exploiting a growing body of preclinical data, showing that PARP inhibitors can suppress DNA repair, and thereby enhancing the anticancer efficacy of various DNA-damaging anticancer therapeutic agents, especially on the background of certain breast cancer mutations, intensive research and development work commenced in the mid 2000s to translate these findings into clinical benefit (see Curtin andSzabó, 2013, Drew, 2015). These efforts resulted in the clinical approval of three PARP inhibitors, olaparib, marketed as Lynparza (Deeks, 2015), rucaparib, marketed as Rubraca and niraparib (MK-4827), marketed as Zejula.…”

Synthesis and Evaluation of a Radioiodinated Tracer with Specificity for Poly(ADP-ribose) Polymerase-1 (PARP-1) in Vivo

“…The combination of PARPi induced deficiency of SSB repair and impaired DSB repair generates synthetic lethality in BRCA mutated cancer cells while healthy tissues with intact BRCA function were not affected. [2][3] Compound 1 (olaparib) ( Figure 1) is a PARPi that has recently been licenced in the EU and US as monotherapy for advanced BRCA deficient ovarian cancer 4 making it the most clinically advanced compound in its class.…”

Effectiveness and Safety of Poly (ADP-ribose) Polymerase Inhibitors in Cancer Therapy: A Systematic Review and Meta-analysis

“…Various inhibitors suppressing PARP enzymes were involved in this study, including Olaparib, Iniparib, and Veliparib. It is worth noting that Olaparib was recently approved for use in human testing by the FDA in 2014 [33]. Will PARP inhibitors be a powerful and safe strategy for personalized cancer treatment in the future?…”