GSK Gains FDA Approval for its PARP Inhibitor Cancer Treatment

May 06, 2020 - GSK recently announced that the FDA approved its PARP inhibitor monotherapy maintenance treatment for women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to chemotherapy. 

Zejula is indicated for patients whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either a deleterious BRCA mutation or genomic instability and progress of more than six months after response to the last platinum-based chemotherapy.

Until now, just 20 percent of women with ovarian cancer or those with BRCA mutation were eligible to be treated with PARP inhibitor as monotherapy in the first-line maintenance setting. 

“Women with advanced ovarian cancer have a five-year survival rate of less than 50%. This expanded indication means that many more women with this devastating disease can receive earlier treatment with Zejula, which can extend the time it takes for their cancer to progress,” Hal Barron, MD, chief scientific officer and president R&D, GSK, said in the announcement. 

According to a study from the University of Pittsburgh and published in Current Medicinal Chemistry, PARP inhibition allows single strand breaks to progress to double-strand break (DSB). In the absence of a functioning hormone receptor (HR), this leads to activation of more error-prone non-homologous end joining (NHEJ). 

A strategy based on this approach would specifically target cells with the primary defect and spare healthy cells. PARP inhibition may be similarly effective in cells in which HR is deficient or impaired, the article concluded. 

The new indication is supported by data from the phase III PRIMA study, which enrolled patients with newly diagnosed advanced ovarian cancer following complete or partial response to chemotherapy, GSK noted.

Zejula is not approved for use in first-line maintenance treatment outside the US.

“PRIMA was designed for patients with ovarian cancer who have a high unmet need. The positive data observed regardless of biomarker status in this study is extremely encouraging and suggests benefit beyond the Bram population,” said Bradley Monk, MD, PRIMA investigator, US oncology, the University of Arizona of Medicine, Phoenix Creighton University School of Medicine at St. Joseph’s Hospital Phoenix. 

“This approval is an important step forward in the treatment of ovarian cancer. In my opinion, maintenance treatment with niraparib should be considered an option for appropriate patients who responded to first-line platinum-based chemotherapy versus active surveillance.”

Patients received 300mg of Zejula once a day, which was later altered based on the patient’s baseline weight and/or platelet count. Researchers stated that the study significantly improved progression-free survival (PFS) for patients treated with Zejula, regardless of biomarker status. 

In the homologous recombination deficient (HRd) population, Zejula saw a 57 percent decrease in the risk of disease progression or death versus placebo and a 38 percent reduction in the risk of disease progression or death versus placebo in the overall population.

The most common grade 3 or higher adverse events that were reported with Zejula were thrombocytopenia (39 percent), anemia (31 percent), and neutropenia (21 percent). 

“It’s so important for patients with ovarian cancer to have treatment options, and this approval is positive news for our community. PARP inhibitors represent a major advancement in the fight against ovarian cancer, and having a new first-line maintenance option for platinum-responsive advanced ovarian cancer patients — regardless of BRCA mutation status — is especially exciting,” said Audra Moran, president and CEO of Ovarian Cancer Research Alliance. 

“We are determined to keep funding research and partnering with scientists who are on the frontline of finding new treatments like this one to help those impacted by this disease.”