FDA Grants Breakthrough Therapy Designation to Niraparib for mCRPC

The agency granted breakthrough therapy designation to niraparib for the treatment of men with BRCA1/2-mutant positive metastatic castration-resistant prostate cancer.

The FDA has granted a breakthrough therapy designation to niraparib (Zejula) for the treatment of men with BRCA1/2-mutant positive metastatic castration-resistant prostate cancer (mCRPC) who have previously received taxane-based chemotherapy and an androgen receptor (AR) inhibitor, according to Janssen, the drug’s developer.

The agency based its action on the PARP inhibitor – which is already approved for use in ovarian and other gynecologic cancers – from an interim analysis of the ongoing, multicenter, open-label phase II GALAHAD trial, designed to evaluate the efficacy and safety of niraparib in patients with mCRPC who have BRCA biallelic DNA-repair gene defects (DRD)and had received treatment with next-generation AR-targeting therapies and docetaxel.

Trial results were recently presented at the European Society of Medical Oncology 2019 Congress

The primary endpoint was objective response rate (ORR), while secondary endpoints included median progression-free survival (PFS) and overall survival (OS). 

As of May 23, among 165 enrolled patients, 81 had biallelic DRD, and a minimum of 16 weeks of follow up, including 29 with BRCAmutant-positive disease and 22 non-BRCA mutant-positive.

The ORR was 41% in the 29 BRCAcases, and it corresponded with a complete response rate (CRR) of 63%. The median duration of the ORR was 5.5 months, and 7 of the 12 BRCA responses were ongoing at the time of reporting. Meanwhile, the non-BRCA group showed a 9% ORR and a 17% CRR.

Janssen said in a statement that they believe niraparib will be an important treatment for certain prostate cancers. 

“Niraparib is a PARP inhibitor that we believe may help address an important unmet need for patients with metastatic castration-resistant prostate cancer who have mutations in DNA-repair genes,” said Kiran Patel, MD, vice president, clinical development, solid tumors, at Janssen Research and Development, LLC. “…we look forward to working with (the FDA) in our continued focus and commitment to bring new advancements to patients diagnosed with prostate cancer.”

Janssen also has other ongoing studies for niraparib in treating prostate cancer. The MAGNITUDE study is a phase III look into the use of the drug with abiraterone acetate (Zytiga) and prednisone versus just abiraterone acetate and prednisone for the treatment of patients with metastatic prostate cancer. The QUEST trial is also underway, a phase Ib/II look into niraparib combination therapies.


Smith MR, Sandhu S, Kelly WK, et al. Pre-specified interim analysis of GALAHAD: a phase 2 study of niraparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and biallelic DNA-repair gene defects (DRD). Presented at: 2019 ESMO Congress; September 27-October 1, 2019; Barcelona, Spain. Abstract LBA50.