GlaxoSmithKline (GSK) announced the submission of a new drug application to the US Food and Drug Administration and new data from two phase III trials for Rezonic/Zunrisa (casopitant), a novel, investigational NK-1 receptor antagonist.

The data demonstrated a significant and clinically meaningful reduction in the number of patients experiencing chemotherapy-induced nausea and vomiting (CINV). Adding a single oral dose regimen of casopitant to the standard dual therapy of Zofran (ondansetron HCI), and dexamethasone, achieved this effect in patients taking highly emetogenic chemotherapy (HEC) and those on moderately emetogenic chemotherapy (MEC) treatment regimens. CINV can be a serious, feared and distressing side effect of chemotherapy for patients and their families. CINV can last for about five days and the risk of nausea and vomiting without prophylaxis is greater than 90 per cent for patients receiving HEC and 30-90 per cent for patients receiving MEC.

Data from the two phase III clinical trials demonstrated complete response rates of 86 per cent for those patients given a single oral dose of casopitant together with the standard dual therapy in the HEC trial, and 73 per cent for patients given either single oral or three-day oral doses of casopitant together with the standard dual therapy in the MEC trial. This prophylactic treatment resulted in clinically meaningful and statistically significant improvement compared to controls. To achieve complete response, patients had no vomiting or retching and took no rescue medications for five days following chemotherapy treatment. These data for the single dose regimen - in addition to results for three-day oral and three-day IV/oral regimens - were unveiled this week at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

"There are many patients who still suffer from the unfortunate side effects of chemotherapy-induced nausea and vomiting in spite of standard dual therapy. Since it is important to make patients as comfortable as possible, I consider these results for casopitant as a very exciting step toward a convenient and effective oral option to provide much needed relief," said study investigator Steven M. Grunberg, M.D., Vermont Cancer Center at University of Vermont and Fletcher Allen Health Care.

Just one or two episodes of CINV can have a significant impact on quality of life and may cause patients to delay or refuse therapy Even with the current treatments available, CINV is still a large burden on patients and their families - up to 40-50 per cent of chemotherapy patients on standard anti-emetic treatment continue to experience breakthrough nausea and vomiting, particularly in the delayed setting.

A new drug application for casopitant was recently submitted to the US Food and Drug Administration for the proposed indication of prevention of chemotherapy induced nausea and vomiting as an add-on therapy to the standard dual therapy of a 5-HT3 receptor antagonist, such as Zofran, and dexamethasone. Applications have been submitted for both the IV and oral formulations. The NDA submission also included the proposed indication of the prevention of postoperative nausea and vomiting. NK-1 receptor antagonists like casopitant complement 5-HT3 receptor antagonists by acting on a different, but also important neurotransmitter system responsible for nausea and vomiting.

"Our goal is not only to eradicate cancer, but also to help patients cope with their cancer and the often unwanted consequences of treatment, such as CINV, that many patients face. Building on our Zofran heritage, casopitant represents our ongoing commitment to advancing cancer care by providing treatments in the supportive arena," said Paolo Paoletti, M.D., senior vice president, Oncology Research, GSK.

Zofran is a highly selective 5-HT3 receptor antagonist used for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting (CINV/RINV), and for the prevention of postoperative nausea and vomiting (PONV). The most commonly reported adverse events in patients receiving Zofran in clinical trials were headache (5% to 27%), diarrhoea (<1% to 16%), constipation (<1% to 9%), fever (<1% to 8%), and malaise/fatigue (0% to 13%).

Casopitant is an NK-1 receptor antagonist in Phase III development in oral and intravenous formulations for multiple indications, including the prevention of chemotherapy-induced nausea and vomiting. Casopitant is an investigational product and has not yet received approval from any regulatory agency.