The FDA criteria for BTD require preliminary clinical evidence that demonstrates a drug may have substantial improvement on at least one clinically significant endpoint over available therapy.
The decision to assign a BTD for Lynparza is based on the results of the TOPARP-A Phase II trial, which found that Lynparza (olaparib) monotherapy in mCPRPC may offer substantial improvement over available therapies for the treatment of the biomarker-selected population with this serious and life-threatening condition.
The TOPARP-A Phase II trial was presented at AACR 2015 and published in the New England Journal of Medicine in October 2015.i It showed that men with prostate cancer with defective DNA damage repair mechanisms responded to Lynparza (olaparib).
The Breakthrough Therapy designation for Lynparza in this patient population means the FDA will expedite review of submission data within 60 days of receipt.
AstraZeneca head of oncology, global medicines development Antoine Yver said: "More than 27,000 men died of prostate cancer last year in the US alone. The Breakthrough Therapy designation for Lynparza is encouraging news for patients, and their families, as there are currently very limited treatment options for metastatic Castration Resistant Prostate Cancer. We will work closely with the FDA to introduce Lynparza as a new treatment option as soon as possible."
Once prostate cancer has progressed to mCPRPC, treatment focuses on extending life, delaying disease progression, and improving symptoms and quality of life.
Overall survival time for patients treated with chemotherapy and newer hormonal agents is 10 months.ii There are also no approved therapies for third line and above (3L+) mCRPC patients, and no targeted therapies are available for mCRPC patients with somatic or germline mutations in BRCA1, BRCA2 or ATM.
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that exploits tumour DNA repair pathway deficiencies to preferentially kill cancer cells. This mode of action gives olaparib the potential for activity in a range of tumour types with DNA repair deficiencies.
Lynparza has been approved by regulatory authorities in 40 countries for the maintenance treatment of women with BRCA-mutated ovarian cancer. AstraZeneca is investigating the potential of olaparib in other PARP dependent tumours.
Phase III studies in gastric cancer, pancreatic cancer and adjuvant and metastatic BRCAm breast cancers are underway, with further studies planned.