AstraZeneca and MSD have announced that a supplemental New Drug Application for Lynparza (olaparib) has been accepted and granted Priority Review in the US for patients with metastatic castration-resistant prostate cancer (mCRPC) and deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene mutations, who have progressed following prior treatment with a new hormonal agent.
A Prescription Drug User Fee Act (PDUFA) date is set for the second quarter of 2020. The Priority Review by the US Food and Drug Administration (FDA) is based on results from the Phase III PROfound trial, which were presented during the Presidential Symposium at the 2019 European Society of Medical Oncology congress.
Results of the PROfound trial showed Lynparza significantly reduced the risk of disease progression or death by 66% based on a hazard ratio of 0.34 (p<0.0001) vs. abiraterone or enzalutamide in patients with BRCA1/2 or ATM-mutated mCRPC, the primary endpoint of the trial.
The trial also showed that Lynparza reduced the risk of disease progression or death by 51% based on a hazard ratio of 0.49 (p<0.0001) vs. abiraterone or enzalutamide in the overall trial population of patients with HRR-mutated (HRRm) mCRPC (those with mutations in the genes for BRCA1/2, ATM, CDK12 or 11 other HRRm genes; key secondary endpoint).
The safety and tolerability profile of Lynparza in the PROfound trial was in line with that observed in previous clinical trials.
Prostate cancer is the second-most common cancer in men, with an estimated 1.3 million new cases diagnosed worldwide in 2018 and is associated with a significant mortality rate. Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone. mCRPC occurs when prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.
Approximately 10-20% of men with advanced prostate cancer will develop CRPC within five years, and at least 84% of these will have metastases at the time of CRPC diagnosis. Of men with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years. Despite an increase in the number of available therapies for men with mCRPC, five-year survival remains low.
Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for the treatment of advanced ovarian cancer, metastatic breast cancer and metastatic pancreatic cancer and has been used to treat more than 30,000 patients worldwide. Lynparza has the broadest and most advanced clinical-trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types.