Zejula Granted FDA’s Breakthrough Therapy Status for Treating Metastatic Castration-resistant Prostate Cancer

The oral ovarian cancer treatment Zejula (niraparib) has been given Breakthrough Therapy status by the U.S. Food and Drug Administration (FDA) for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who carry BRCA mutations and have been previously treated with certain therapies, namely taxane chemotherapy and androgen-receptor targeted therapy.

Breakthrough Therapy designation is expected to accelerate the development and regulatory review of an investigational treatment that’s intended to treat a serious or life-threatening condition. The designation is given when preliminary evidence supports significant benefits of the new therapeutic candidate compared to available treatments.

The FDA based its decision on a preliminary analysis of the ongoing GALAHAD study (NCT02854436), a Phase 2, open-label clinical trial running in multiple countries worldwide and sponsored by Janssen, a company owned by Johnson & Johnson.

The study is evaluating the efficacy and safety of Zejula for the treatment of adults with mCRPC and gene defects in DNA-repair pathways (e.g. BRCA mutations) and whose cancer is hard to treat. Participants have received prior treatment with next-generation androgen-receptor targeting therapies (e.g. Zytiga plus prednisone, Xtandi, Erleada) and the chemotherapy docetaxel.

Positive interim data from GALAHAD was recently presented at the European Society for Medical Oncology (ESMO) 2019 Congress, in Barcelona, in a poster titled “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).”

Among the 165 enrolled patients so far, 81 had a defect in both copies of a DNA repair pathway gene, including 46 with BRCA1/2 mutations — the most common in people with mCRPC — and 35 with alterations in other genes. The minimum follow-up was 16 weeks.

Researchers assessed disease responses in patients whose tumors were measurable at the study’s start. For those with BRCA1/2 mutations, Zejula reduced tumor burden in 41% of patients and led to a 63% composite response rate, defined as a reduction in tumor burden or quantity of circulating tumor cells, or 50% or greater reduction in prostate-specific antigen levels.

Patients positive for BRCA1/2 mutations lived a median of 8.2 months without radiographic progression of the disease. Median overall survival was 12.6 months.

For patients with non-BRCA mutations, Zejula shrunk the tumors in 9% of the patients and led to a composite response in 17%. These patients lived without disease progression for a median of 5.3 months, and their overall survival was 14 months.

Zejula “demonstrates clinical activity in [patients] with treatment-refractory mCRPC with durable responses, particularly in biallelic BRCA mutation carriers,” the researchers wrote.

The study updates are in line with earlier findings presented at this year’s American Society of Clinical Oncology Genitourinary Cancers Symposium. Patient enrollment for GALAHAD is still open. For more information, visit the official site here.

Zejula is an orally-administered poly ADP-ribose polymerase (PARP) inhibitor, which is indicated in the U.S. for the maintenance treatment of certain adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. The medication is marketed by Tesaro, a GSK company. In April 2016, Janssen entered a worldwide (excluding Japan) collaboration and license agreement with Tesaro for exclusive rights to Zejula for treating prostate cancer.

“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,” Kiran Patel, MD, Janssen’s vice president of clinical development, solid tumors, said in a news release.

“We are pleased with the FDA’s Breakthrough Therapy Designation as we continue the clinical development of niraparib, and we look forward to working with the agency in our continued focus and commitment to bring new advancements to patients diagnosed with prostate cancer,” Patel added.

Janssen is currently running two other studies as part of its clinical development of Zejula for metastatic prostate cancer: the MAGNITUDE Phase 3 trial (NCT03748641), which is testing Zejula plus Zytiga (abiraterone acetate) and prednisone; and QUEST, a Phase 1b/2 trial (NCT03431350) evaluating Zejula-based combination therapies for the treatment of mCRPC.

Both trials are currently recruiting patients in several countries worldwide. For more information on contacts and locations, click on the trials’ identifiers.