Date: 2017-11-16
Type of information: Granting of a Market Authorisation in the EU
Product name: Zejula®
Compound: niraparib
Therapeutic area: Cancer - Oncology
Action mechanism:
- poly ADP ribose polymerase PARP inhibitor/PARP inhibitor. Niraparib is an orally administered poly polymerase (PARP) inhibitor, currently in late-stage development for patients with metastatic breast cancer and ovarian cancer. PARP proteins play a key survival role in DNA repair in cancer cells. By inhibiting PARP, certain defective cancer cells are not able to repair themselves, leading to cell death. A portion of men with prostate cancer have these defective cancer cells and may benefit from use of a PARP inhibitor, either alone, or in combination with other treatments.
Company: Tesaro (USA - MA)
Disease: recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer
Latest news:
- • On September 14, 2017, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for the marketing authorization application 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 a complete response or partial response to platinum-based chemotherapy. Pending the decision by the EC, Zejula® would be the first oral, once-daily poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor approved in Europe for use in patients regardless of BRCA mutation or biomarker status. The marketing authorization application is supported by data from the ENGOT-OV16/NOVA trial that enrolled 553 patients with recurrent ovarian cancer who had achieved either a partial response or complete response to their most recent platinum-based chemotherapy. Approximately two-thirds of study participants did not have germline BRCA mutations. Treatment with Zejula® reduced the risk of disease progression or death by 73% in patients with germline BRCA mutations (HR 0.27) and by 55% in patients without germline BRCA mutations (HR 0.45). The magnitude of benefit was similar for patients entering the trial with a partial response or a complete response.
- • On April 19, 2017, Tesaro announced that Zejula® (niraparib) is now available by prescription in the United States. The National Comprehensive Cancer Network (NCCN) recently added Zejula® to the NCCN Clinical Practice Guidelines in Oncology Ovarian Cancer version 1.2017—April 12, 2017—as maintenance therapy for patients with platinum-sensitive disease who are in partial or complete response after completion of two or more lines of platinum-based therapy.
- • On March 27, 2017, Tesaro announced that the FDA
has approved Zejula® (niraparib) for the maintenance treatment of women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum based
chemotherapy. The drug is the first PARP inhibitor to be approved by the FDA that does not require BRCA mutation or other biomarker testing. Tesaro anticipates launching Zejula® in the United States in late April.
- FDA approval of the drug is based upon data from the international Phase 3 ENGOTOV16/NOVA trial
- The median progression-free survival for patients taking Zejula® who had a germline BRCA mutation was 21 months compared to 5.5 months for the same patient population taking a placebo.
- The median progression-free survival for patients taking Zejula® who did not have a germline BRCA mutation was 9.3 months compared to 3.9 months for the same patient population taking a placebo.
- Treatment with Zejula® reduced the risk of disease progression or death by 74% in patients with germline BRCA
mutations (HR 0.26) and by 55% in patients without germline BRCA mutations (HR 0.45). The magnitude of benefit was similar for patients entering the trial with a PR or a CR.
- The most common grade 3/4 adverse reactions to Zejula® in the NOVA trial included thrombocytopenia (29%), anemia (25%), neutropenia (20%), and hypertension (9%). The majority of hematologic adverse events were successfully managed via dose modification, and discontinuation of therapy due to thrombocytopenia, neutropenia and anemia occurred in 3.3%, 1.9% and 1.4% of patients, respectively. Following dose adjustment based on individual tolerability,
the incidence of grade 3/4 thrombocytopenia was low; approximately <1% after month 2. A Marketing Authorisation Application for niraparib is under review by the European
Medicines Agency (EMA).
- • On November 1, 2016, Tesaro announced that it has completed the niraparib rolling New Drug Application (NDA) submission to the FDA for the maintenance treatment of patients with platinum-sensitive, recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum-based chemotherapy.
- The niraparib NDA is supported by data from the ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled, international Phase 3 study that enrolled 553 patients with recurrent ovarian cancer who were in response to their most recent platinum-based chemotherapy. The trial successfully achieved its primary endpoint in both patient cohorts, demonstrating that niraparib treatment significantly prolonged PFS compared to control. The full results of the ENGOT-OV16/NOVA trial were presented in detail at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen on October 8, 2016 and were published simultaneously in The New England Journal of Medicine. Based upon the results of this trial, the indication proposed in the NDA provides for the use of niraparib regardless of tumor biomarker status, and it is anticipated that the BRACAnalysis® CDx and myChoice® HRD tests would be available to physicians as complementary diagnostics.
- • On October 27, 2016, Tesaro announced that the Marketing Authorisation Application (MAA) for niraparib has been submitted to and accepted for review by the European Medicines Agency (EMA) for the maintenance treatment of patients with platinum-sensitive, recurrent ovarian cancer who are in response to platinum-based chemotherapy. With this acceptance, the review of the niraparib marketing authorisation application in the Centralised Procedure will now begin.
- • On September 12, 2016, Tesaro announced that the FDA has granted Fast Track designation to niraparib for the treatment of patients with recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer. Tesaro has initiated a rolling submission of a New Drug Application (NDA) for niraparib to the FDA, and intends to complete this submission during the fourth quarter.
Patents:
Submission of marketing authorization application USA : 2016-11-01
Submission of marketing authorization application UE: 2016-10-27
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-03-27
UE authorization: 2017-11-16
Favourable opinion UE: 2017-09-14
Favourable opinion USA:
Orphan status USA: 2010-04-30
Orphan status UE: 2010-08-04
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
