The Chinese regulatory agency has agreed to review Zai Lab‘s application asking that Zejula (niraparib) be approved as first-line maintenance therapy for women with ovarian cancer who are responding to platinum-based chemotherapy, the company announced.
The supplemental New Drug Application (sNDA), submitted to the China National Medical Products Administration (NMPA), is for women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.
It follows a similar request for Zejula as a first-line treatment for these patients, made to the U.S. Food and Drug Administration in February by GlaxoSmithKline (GSK) and taken under review.
“The NMPA’s acceptance of our sNDA submission for Zejula as a first-line monotherapy treatment after surgery and platinum-based chemotherapy has the potential to both fundamentally change how women with ovarian cancer are treated in China and significantly expand Zejula’s market opportunity,” Samantha Du, founder and chief executive officer of Zai Lab, said in a press release.
Zejula is an oral therapy that works by blocking the activity of PARP enzymes, which are involved in DNA repair. By blocking these enzymes, Zejula prevents cancer cells from repairing their DNA, eventually killing them.
In the U.S., the therapy is marketed by Tesaro, a GSK subsidiary. Under a license agreement with GSK, Zai Lab owns the rights to Zejula in mainland China, Hong Kong, and Macau. In those countries, as in the U.S., its approval includes use as a maintenance treatment of patients who failed prior therapies, but are currently responding to platinum-based chemotherapy.
The supplemental application, in China and the U.S., is based on clinical data from the PRIMA Phase 3 trial (PRIMA/ENGOTOV26/GOG-3012; NCT02655016).
The trial enrolled 733 women with newly diagnosed advanced ovarian cancer, with or without BRCA mutations. All were responding to first-line platinum-based chemotherapy and were at high risk for relapse.
Within 12 weeks of completing the last dose of chemotherapy, these women were randomized to either 300 mg of Zejula (487 patients) or placebo (246 patients), given once for 36 months or until disease progression.
Half the patients (51%) had tumors positive for homologous recombination deficiency (HRD), a parameter used to identify people most likely to benefit from PARP inhibitors.
HDR status was assessed using Myriad‘s myChoice test, which is also under FDA review as the test of choice to identify chemo-responsive patients likely to benefit from Zejula as a maintenance therapy.
In the overall patient population, Zejula significantly extended the time people lived with no signs of disease progression (progression-free survival, PFS) compared to patients given a placebo — a median of 13.8 months versus 8.2 months. This meant a 38% lower risk of disease progression or death among those given Zejula.
When looking at patients with HRD-positive tumors (including those with BRCA mutations), the survival benefit was even greater: patients treated with Zejula had a median PFS of 21.9 months compared to 10.4 months for a placebo. This corresponded to a 57% reduction in the risk of disease progression or death.
The most common treatment related side effects graded as severe or worse were low red blood cell counts (31.0%), low platelet counts (28.7%), and low levels of neutrophils (a type of white blood cell, 12.8%). No treatment-related deaths occurred.
Zejula is able to cross the blood brain barrier, a highly selective membrane that shields the central nervous system (brain and spinal cord) from general blood circulation. This ability suggests it may help fight brain metastasis in ovarian cancer patients.
“We believe Zejula is a potential best-in-class PARP inhibitor due to its compelling efficacy, once-daily dosing and superior pharmacokinetic properties including its ability to cross the blood brain barrier,” Du said.