TESARO, an oncology focused biopharmaceutical company, announced that the European Commission (EC) has granted marketing authorization for ZEJULA (niraparib) as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete response (CR) or partial response (PR) to platinum-based chemotherapy. ZEJULA is the first once-daily, oral poly (ADP-ribose) polymerase (PARP)1/2 inhibitor to be approved in Europe that does not require BRCAmutation or other biomarker testing.
“We want to express our gratitude to all of the women who selflessly participated in the ZEJULA clinical development program. I would also like to thank our partners at ENGOT for their diligence in conducting the ENGOT-OV16/NOVA trial, which was carried out with the highest level of scientific rigor. The unique design of this trial, which included women both with and without germline BRCA mutations, allowed us to independently determine that ZEJULA provides significant progression-free survival improvement in a very broad patient population,” said Mary Lynne Hedley, Ph.D., President and Chief Operating Officer of TESARO. “The EC approval of ZEJULA marks TESARO’s second product approval in Europe this year. We are committed to working with healthcare providers, payers and patient groups to enable access to this paradigm-changing treatment as quickly as possible.”
ZEJULA was approved by the FDA on March 27, 2017 and is marketed by TESARO in the United States, where it is currently the most frequently prescribed PARP inhibitor for patients with ovarian cancer. TESARO plans to launch ZEJULA in Germany and the UK this December, with launches in additional European countries to follow beginning in 2018, based on local reimbursement and availability timelines. Germany and the UK are two of the 17 countries where TESARO currently has a direct presence in Europe.
“Today’s approval of ZEJULA is an exciting step forward for the ovarian cancer community in Europe. While platinum-based chemotherapy has proven to be effective, its efficacy unfortunately diminishes over time, and progression-free survival becomes shorter after each successive platinum treatment,” said Mansoor Raza Mirza, M.D., ENGOT-OV16/NOVA Study Chair and Chief Oncologist at Rigshospitalet, Copenhagen. “ZEJULA now provides an opportunity to increase progression-free survival after platinum therapy, and will have a profound impact for women and their families.”
The EC approval of ZEJULA was based on data from the clinically rigorous ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled, international Phase 3 study of ZEJULA that enrolled 553 patients with recurrent ovarian cancer who had achieved either a PR or CR to their most recent platinum-based chemotherapy. The primary endpoint of the trial was progression free survival (PFS). Approximately two-thirds of study participants did not have germline BRCA mutations. Progression in the NOVA study was determined by a robust, unbiased, blinded central review to be the earlier of radiographic or clinical progression. ZEJULA significantly increased PFS in patients with or without germline BRCA mutations as compared to the control arm. Treatment with ZEJULA reduced the risk of disease progression or death by 73% in patients with germline BRCAmutations (hazard ration (HR) 0.27) and by 55% in patients without germline BRCAmutations (HR 0.45). The magnitude of benefit was similar for patients entering the trial with a PR or a CR.
“With the introduction of ZEJULA, treatment of women with recurrent ovarian cancer will improve markedly,” said Professor Dr. Andreas Du Bois, Center Director of Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte (Germany) and Co-Founder and Past Chair of the European Network of Gynecological Oncological Trial Groups (ENGOT). “Patients and their physicians are now empowered with an additional option to utilize after a response to chemotherapy, regardless of BRCA mutation status, where the previous alternative for most was a period of watching and waiting instead of actively controlling their disease.”
The approved starting dose of ZEJULA is 300 milligrams once per day. According to the European summary of product characteristics (SmPC), in patients below 58 kilograms, a starting dose of 200 milligrams once per day may be considered. The most commonly administered dose of ZEJULA over the course of the Phase 3 NOVA clinical trial was 200 milligrams once per day, following dose modification. Further exploratory analyses of the NOVA study indicated that individual dose modification maintained efficacy and reduced the rate of new adverse events1.
The most common grade 3/4 adverse reactions to ZEJULA included thrombocytopenia (34%), anemia (25%), neutropenia (20%), and hypertension (8%). Following dose adjustment based on individual tolerability, the incidence of grade 3/4 thrombocytopenia was low, approximately 1% after month three. The majority of hematologic adverse events were successfully managed via dose modification, and discontinuation of therapy due to thrombocytopenia, neutropenia and anemia occurred in 3%, 2% and 1% of patients, respectively.
“We welcome the decision by the EC to approve ZEJULA for women with recurrent ovarian cancer,” said Elisabeth Baugh, Chair of the World Ovarian Cancer Coalition. “This decision will have a real and meaningful impact on women's lives, providing them a new treatment option and greater choice. Globally, we are lacking effective treatments for ovarian cancer, so this is a much-needed addition.”