GSK’s Zejula (Niraparib) Approved in EU as First-Line Monotherapy Maintenance Treatment for Platinum-Sensitive Advanced Ovarian Cancer Regardless of Biomarker Status

October 30, 2020 /Bio ValleyBIOON/ --GlaxoSmithKline(GSK) recently announced that the European Commission (EC) has approved Zejula (Chinese brand name: Zeler, generic name: niraparib), a targeted anticancer drug, as a first-line monotherapy maintenance treatment for patients with advanced ovarian cancer (including epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer) who have achieved complete or partial response after platinum-based chemotherapy, regardless of theirBiomarkersStatus update. In terms of U.S. regulatory affairs, in late April this year, the supplemental New Drug Application (sNDA) for Zejula for the same indication was approvedFDAApproved.

Notably, this approval makes Zejula the first single-agent PARP inhibitor in the European Union for first-line maintenance treatment of patients with advanced ovarian cancer who have responded to platinum-based chemotherapy, marking a significant advancement in the treatment of ovarian cancer. Previously, only 20% of ovarian cancer patients—those with BRCA mutations (BRCAm)—were eligible for single-agent PARP inhibitor therapy as first-line maintenance treatment.

This approval was supported by the results of the Phase III PRIMA study (ENGOT-OV26/GOG-3012). In this study, patients with advanced-stage (Stage III or IV) disease who achieved a response to first-line platinum-based chemotherapy were randomized in a 2:1 ratio to receive maintenance therapy with Zejula or placebo. The primary endpoint was progression-free survival (PFS). The study incorporated an individualized starting dose regimen for Zejula: patients with a baseline body weight <77 kg and/or a platelet count <150K/μL received a starting dose of 200 mg once daily; all other patients received a starting dose of 300 mg once daily.

Data show that in the homologous recombination deficiency (HRd) population, the entire study population (regardless ofBiomarkersIn the BRCA-mutated population, Zejula as first-line monotherapy maintenance treatment reduced the risk of disease progression or death by 57% (HR=0.43; 95% CI: 0.31–0.59; p<0.0001), 38% (HR=0.62; 95% CI: 0.50–0.76; p<0.001), and 60% (HR=0.40; 95% CI: 0.27–0.62; p<0.001), respectively, compared with placebo.

The safety profile demonstrated in this study was consistent with the previously observed clinical safety profile of Zejula. Compared with the overall population, the incidence of Grade 3/4 hematologic treatment-emergent adverse events (TEAEs) was lower with the implementation of an individualized dosing regimen based on body weight and/or platelet count, including thrombocytopenia (21% vs. 39%),Anemia(23% vs 31%) and neutropenia (15% vs 21%). Validated patient-reported outcomes indicated that quality of life was similar between the Zejula treatment group and the placebo group.

Globally, ovarian cancer is the eighth most common cause of cancer-related death among women. In the United States and Europe, approximately 22,000 and 65,000 women are diagnosed with ovarian cancer each year, respectively. Although first-line platinum-based chemotherapy has a high response rate, approximately 85% of patients will experience disease recurrence. Once recurrent, the disease is difficult to cure, and the interval between recurrences shortens with each relapse.

The PRIMA study enrolled patients who responded to first-line platinum-based chemotherapy, including those at high risk of disease progression—a population with significant unmet medical needs that has been underrepresented in previous first-line ovarian cancer studies. This landmark study demonstrated the importance of Zejula as first-line maintenance therapy and its clinical benefits for women with ovarian cancer. Monotherapy with Zejula as first-line maintenance treatment following surgery and first-line platinum-based chemotherapy provides patients with an important new therapeutic option, potentially fundamentally transforming the treatment paradigm for ovarian cancer.

The active pharmaceutical ingredient of Zejula is niraparib, an oral small-molecule poly(ADP-ribose) polymerase (PARP) inhibitor that leverages defects in DNA repair pathways to preferentially kill cancer cells. This mechanism of action endows the drug with the potential to treat a broad range of tumors harboring DNA repair deficiencies. PARP is associated with a wide spectrum ofTumorType-related, especiallyBreast Cancerand ovarian cancer. Zejula was developed by Tesaro,GlaxoSmithKlineIn December 2018, Tesaro was acquired for $5.1 billion (approximately £4 billion). In late September 2016, Zai Lab entered into a licensing agreement with Tesaro, securing the rights to Zejula in mainland China, Hong Kong, and Macau.

Zejula was approved for marketing in March 2017. The currently approved indications include: (1) maintenance treatment of patients with recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have achieved a complete or partial response to platinum-based chemotherapy. (2) Treatment of patients with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have previously received three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either of the following two criteria: (a) deleterious or suspected deleterious BRCA mutation; (b) genomic instability score (GIS) positivity and disease progression more than 6 months after responding to the last platinum-based chemotherapy.

In Hong Kong and Macau, China, Zejula (Zele) was approved for marketing in October 2018 and June 2019, respectively. In mainland China, the National Medical Products Administration (NMPA) approved Zejula (Zele) on December 27, 2019. The drug is indicated for maintenance treatment of adult patients with recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have achieved a complete or partial response to platinum-based chemotherapy. (Bioon.com)

Original source: European Commissionapproves Zejula (niraparib) as first-line monotherapy maintenance treatment in advanced ovarian cancer