NEW YORK – The US Food and Drug Administration has approved GlaxoSmithKline's PARP inhibitor niraparib (Zejula) as a first-line maintenance treatment for women with platinum-responsive advanced ovarian cancer regardless of their biomarker status.
Less than 50 percent of women with advanced ovarian cancer live for five years. "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," GSK CSO Hal Barron said in a statement.
In the Phase III PRIMA trial, data from which supported the latest approval, advanced ovarian cancer patients were stratified based on their homologous recombination deficiency (HRD) status using Myriad Genetics' myChoice CDx. Myriad had filed a supplementary premarket approval application in this setting for myChoice CDx earlier this year.
A Myriad spokesperson said that the FDA has approved its test as a complementary diagnostic and noted that myChoice CDx "helps identify those women with ovarian cancer who are most likely to benefit from PARP inhibitors." According to the FDA, a companion diagnostic is essential for the safe and effective use of a drug. While a complementary diagnostic is not essential, it can still be useful for guiding treatment strategy.
"We will be actively working with all stakeholders to raise awareness so that patients can be tested to determine if they are likely to benefit from these targeted therapies," said Ron Rogers, Myriad's executive VP of corporate communications.
The messaging from GSK, meanwhile, will underscore the broader utility of niraparib. Ahead of submitting its supplementary new drug application with the FDA earlier this year, GSK executives made clear that based on results from the PRIMA trial they would pursue an indication in the first-line ovarian cancer maintenance setting for niraparib that would not require biomarker testing.
Data from that study, which was published in the New England Journal of Medicine, showed that newly diagnosed advanced ovarian cancer patients had longer median progression-free survival on niraparib compared to placebo (13.8 months versus 8.2 months), regardless of their HRD status.
The latest approval makes niraparib the only PAPR inhibitor that can be marketed as a first-line maintenance monotherapy to all advanced, platinum-sensitive ovarian cancer patients. For example, AstraZeneca's PARP inhibitor olaparib (Lynparza), is approved in this setting for women who harbor BRCA1/2 mutations. GSK estimated that prior to the latest approval of niraparib, only 20 percent of ovarian cancer patients had access to PARP inhibitor monotherapy in the first-line maintenance setting based on their BRCA1/2 mutation status.
The PRIMA study, however, also showed that patients with HRD, as determined by myChoice CDx, derived a greater magnitude of benefit than those without this biomarker. Niraparib-treated patients with HRD had a 57 percent reduction in the risk of disease progression or death compared to placebo. In comparison, in the overall population, niraparib treatment reduced the risk of progression or death by 38 percent compared to placebo.
MyChoice CDx sequences BRCA1 and BRCA2 genes, and measures three other processes involved in DNA repair: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions. In October, the FDA approved niraparib as a fourth-line treatment for ovarian cancer patients who are platinum sensitive and have HRD. The agency approved myChoice CDx alongside niraparib in this setting to identify patients with HRD who might respond best to treatment.
Myriad is also seeking FDA approval for myChoice CDx as a companion diagnostic to identify advanced ovarian cancer patients with HRD who are likely to benefit from the combination of olaparib and bevacizumab (Genentech's Avastin) in the first-line maintenance setting. The FDA is slated to issue a decision before year end.