- ZEJULA is the first PARP inhibitor approved in
Europefor women with recurrent ovarian cancer, regardless of BRCA mutation or biomarker status
- Approval supported by robust data from a randomized, well-controlled Phase 3 trial
- Only PARPi to offer once-daily, oral dosing to enable convenient administration for maintenance treatment
- First commercial launches planned for
Germanyand the UKthis December
A PDF accompanying this announcement is available at
“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
ZEJULA was approved by the
“Today’s approval of ZEJULA is an exciting step forward for the ovarian cancer community in
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 BRCA mutations (hazard ration (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 PR or a CR.
“With the introduction of ZEJULA, treatment of women with recurrent ovarian cancer will improve markedly,” said Professor Dr.
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
About the ZEJULA® (niraparib) ENGOT-OV16/NOVA Clinical Trial
ENGOT-OV16/NOVA was a double-blind, placebo-controlled, international Phase 3 trial of niraparib that enrolled 553 patients with recurrent ovarian cancer who were in a response to their most recent platinum-based chemotherapy. Patients were enrolled into one of two independent cohorts based on germline BRCA mutation status. One cohort enrolled patients who were germline BRCA mutation carriers (gBRCAmut), and the second cohort enrolled patients who were not germline BRCA mutation carriers (non-gBRCAmut) and included patients with HRD-positive and HRD-negative tumors. Within each cohort, patients were randomized 2:1 to receive niraparib or placebo and were treated continuously with placebo or 300 milligrams of niraparib, dosed as three 100 milligram tablets once per day, until progression. The primary endpoint of this study was progression-free survival (PFS). Secondary endpoints included patient-reported outcomes, chemotherapy-free interval length, PFS 2, overall survival, and other measures of safety and tolerability. More information about this trial is available at http://clinicaltrials.gov/show/NCT01847274.
Among patients who were germline BRCA mutation carriers, the niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a HR of 0.26 (95% CI, 0.173-0.410). The median PFS for patients treated with niraparib was 21.0 months, compared to 5.5 months for control (p<0.0001). Niraparib also showed statistical significance for patients in the non-germline BRCA mutation cohort. The niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a HR of 0.45 (95% CI, 0.338-0.607). The median PFS for patients treated with niraparib was 9.3 months, compared to 3.9 months for control (p<0.0001). Secondary endpoint analyses, including chemotherapy-free interval, time to first subsequent treatment, and PFS 2 were all statistically significant and favored niraparib over control for patients in both the gBRCAmut and non-gBRCAmut cohorts. Patient-reported outcome results from validated survey tools indicated that niraparib-treated patients reported no difference from control in measures associated with quality of life.
The full results of the ENGOT-OV16/NOVA trial were presented in detail at the
Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in patients treated with ZEJULA. Discontinue ZEJULA if MDS/AML is confirmed.
Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with ZEJULA. Monitor complete blood counts (CBCs) weekly for the first month of treatment and modify the dose as needed. After the first month, it is recommended to monitor CBCs for the next 10 months of treatment, and periodically after this time. Based on individual laboratory values, weekly monitoring for the second month may be warranted.
Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA. Pre-existing hypertension should be adequately controlled before starting ZEJULA. Monitor blood pressure monthly for the first year and periodically thereafter during treatment with ZEJULA. ZEJULA should be discontinued in case of hypertensive crisis or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy.
Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the possible risk to a fetus and to use effective contraception during treatment and for six months after receiving the final dose. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for one month after receiving the final dose.
In clinical studies, the most common adverse reactions included: thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, abdominal pain, diarrhea, dyspepsia, urinary tract infection, fatigue/asthenia, decreased appetite, headache, dizziness, dysgeusia, palpitations, insomnia, nasopharyngitis, dyspnea, cough, and hypertension.
Additional Clinical Trials of Niraparib
Additional trials of niraparib in ovarian, breast and lung cancers are planned. The studies will assess the effect of niraparib alone and in combination with other therapies in a variety of treatment settings.
Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in
About Ovarian Cancer in
About ZEJULA (niraparib)
ZEJULA is a once-daily, oral poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor that is indicated in the
Forward Looking Statements
To the extent that statements contained in this press release are not descriptions of historical facts regarding
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1 Wang J et al. The Exposure-Response Relationship of Niraparib in Patients with gBRCAmut and Non-gBRCAmut: Results from the ENGOT-OV16/NOVA Trial. ESMO; 2017
3 EUCAN http://eco.iarc.fr/eucan/Country.aspx?ISOCountryCd=930 (Last accessed
4 ENGAGe, Ovarian Cancer Fact Sheet. https://engage.esgo.org/media/2017/08/ENGAGe_What_is_ovarian_cancer_en_V01.pdf (Last accessed 18 November 2017)
5 Lorusso, D., Mancini, M.,
Source: TESARO, Inc.