The European Commission has approved Zejula (niraparib) as a first-line maintenance therapy for people with advanced ovarian, fallopian tube, or primary peritoneal cancer, who respond to platinum-based chemotherapy.
This decision follows a positive recommendation issued by the Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency (EMA).
Zejula is now the first PARP inhibitor to be approved in Europe as a stand-alone therapy for women with advanced ovarian cancer, regardless of whether their tumors are defective in DNA repair genes.
“Over 65,000 women in Europe are diagnosed with ovarian cancer each year. This approval of Zejula means that many more women will have the option to receive this innovative medicine earlier, potentially extending the time they may spend without their devastating cancer progressing,” Hal Barron, chief scientific officer and president of Research and Development at GlaxoSmithKline (GSK), said in a press release.
Zejula, marketed by Tesaro (a GSK subsidiary), works by blocking the activity of PARP enzymes needed for DNA repair. By inhibiting their activity in cancer cells, Zejula effectively prevents these cells from repairing their DNA, eventually killing them. Due to this mechanism, PARP inhibitors like Zejula tend to be more effective in patients whose tumors contain mutations in DNA repair genes, such as the BRCA genes.
The oral therapy had already been approved in the U.S. and Europe as a maintenance therapy for people with recurrent and high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer, who were responding at least partly to platinum-based chemo.
In April, the U.S. Food and Drug Administration (FDA) also approved Zejula as a first-line, maintenance therapy for adults with advanced, platinum-responsive ovarian, fallopian tube, or primary peritoneal cancer, regardless of their tumor mutation status. This indication is now also approved in Europe.
Both approvals were based on data from the pivotal Phase 3 PRIMA trial (ENGOTOV26/GOG-3012; NCT02655016), assessing the safety and efficacy of Zejula, compared with a placebo, when given as a maintenance therapy to people with newly diagnosed advanced ovarian cancer who responded to first-line platinum-based chemo.
Its main goal was evidence that Zejula could prolong the time these patients lived without disease worsening. This endpoint was assessed in trial’s overall population of 733 women, as well as in a subset of 374 patients whose tumors contained DNA repair gene mutations.
Top-line data from PRIMA showed that Zejula significantly prolonged the time treated patients — compared with those given a placebo — lived without worsening, regardless of whether their tumors were defective in DNA repair genes.
In the overall population, Zejula extended the time without disease progression from a median of 8.2 (placebo group) to 13.8 months, lowering the risk of death or disease worsening by 38%.
These benefits were even stronger in the subgroup whose tumors contained mutations in DNA repair genes. Here, Zejula increased the median time treated patients lived without worsening from 10.4 (placebo group) to 21.9 months, lowering the risk of death or disease progression by 57%.
Treatment responses were also found to be strong and durable in all women enrolled in the study, regardless of tumor mutation status.
“Having a new first-line maintenance option for patients with platinum-responsive advanced ovarian cancer in Europe — regardless of BRCA mutation status — speaks to the important role of PARP inhibitors in the fight against ovarian cancer,” said Clara MacKay, CEO of the World Ovarian Cancer Coalition.
“Until now, only women with BRCA-mutant (BRCAm) ovarian cancer, representing just 20% of patients with advanced ovarian cancer, were eligible to be treated with a PARP inhibitor as monotherapy in the first-line maintenance setting,” added Antonio Gonzalez-Martin, primary investigator for PRIMA. “Expanding the potential use of Zejula, regardless of biomarker status, is an important step forward in treating this challenging cancer.”
“We are especially delighted that today’s approval means that more women in Europe who are diagnosed with ovarian cancer will have this new treatment option. We appreciate the commitment and scientific leadership required to develop innovative new therapies that address unmet needs in women’s cancer,” MacKay added.
The therapy’s safety profile in PRIMA was also consistent with that of previous studies. Importantly, lower rates of severe (grade 3) and life-threatening (grade 4) blood abnormalities, including low platelet counts, anemia, and low white blood cell counts, were observed when women started receiving an individualized starting dose of Zejula.
This individualized regimen, in which Zejula was given once daily at a dose of 200 or 300 mg based on patients’ body weight and/or platelet count, replaced the study’s original fixed dose regimen of a once daily, 300 mg dose. Based on these findings, the medication’s European prescribing information, like that for the U.S., includes the individualized starting dose regimen.