Date: 2014-07-10
Type of information: Publication of results in a medical journal
phase: 2-3
Announcement: publication of results in the Annals of Oncology
Company: Helsinn (Switzerland) Eisai (Japan)
Product: oral fixed-dose combination capsule of netupitant 300 mg + palonosetron 0.50 mg (NEPA)
Action
mechanism: NEPA is an investigational single-day, fixed-dose combination of a selective NK1 receptor antagonist, netupitant, and a 5-HT3 receptor antagonist, palonosetron, designed to target two critical pathways thought to be associated with chemotherapy-induced nausea and vomiting (CINV).
Disease: prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) following both highly and moderately emetogenic chemotherapy
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On July 10, 2014, Helsinn Group, the company focused on building quality cancer care, announced that the complete results of the three Phase 2/3 pivotal trials for the investigational oral fixed-dose combination capsule of netupitant 300 mg + oral palonosetron 0.50 mg (NEPA), which is licensed to Eisai Inc. in the United States, have been published, together with an accompanying editorial, in the July issue of Annals of Oncology. The first study (Hesketh, et al) was a pivotal, Phase 2, randomized, double-blind, dose-ranging study in 694 patients undergoing cisplatin-based, highly emetogenic chemotherapy. Three different doses of oral netupitant (100, 200 and 300 mg) in combination with oral palonosetron (0.50 mg) plus dexamethasone were compared with oral palonosetron (0.50 mg) plus dexamethasone. All NEPA doses showed significantly higher overall (0-120 hour) complete response rates (no emesis, no rescue medication), the primary endpoint, compared with oral palonosetron, with the highest NEPA (300 mg) dose studied showing an incremental benefit over lower NEPA doses for all efficacy endpoints. On the basis of these results, this dose combination was selected for continued development. The second study (Aapro, et al) was a multinational, randomized, double-blind, parallel-group Phase 3 study in 1455 chemotherapy-naïve patients receiving anthracycline-cyclophosphamide moderately emetogenic chemotherapy. Patients were randomized to receive either oral NEPA plus dexamethasone or oral palonosetron plus dexamethasone, all administered only on Day 1 prior to chemotherapy. The percentage of patients who met the primary endpoint of complete response in the delayed (25-120 hours) phase was significantly higher in the NEPA group compared with the oral palonosetron group, which was also seen in the acute (0-24 hours) and overall (0-120 hours) phases post chemotherapy. The third multinational, double-blind, Phase 3 study (Gralla, et al) in 413 patients was designed primarily to demonstrate the safety of NEPA over multiple cycles of either highly (24% of patients) or moderately emetogenic chemotherapy (76% of patients). Patients were randomly assigned (at a 3:1 ratio) to receive NEPA plus dexamethasone or aprepitant plus oral palonosetron and dexamethasone. Patients completed 1961 total chemotherapy cycles with 75% of patients completing ?4 cycles. The adverse event profile was consistent with that expected for patients undergoing cytotoxic chemotherapy, with the most frequently reported treatment-related events being headache and constipation. NEPA is currently under review by the FDA and the European Medicines Agency (EMA).
