FDA Approves EMEND® , in Combination with Other Antiemetics, for the Prevention of Nausea and Vomiting in Cancer Patients Undergoing Moderately Emetogenic Chemotherapy

Business Wire, Jan 11, 2006

WHITEHOUSE STATION, N.J. -- Merck & Co., Inc. announced today that the Food and Drug Administration (FDA) has approved EMEND(R) (aprepitant) for use with other antiemetic medicines for the prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy, which are likely to cause nausea and vomiting. EMEND, in combination with other antiemetics, is also approved for the prevention of nausea and vomiting caused by initial and repeat courses of highly emetogenic chemotherapy treatments, which are highly likely to cause nausea and vomiting, including high dose cisplatin.

The FDA approval for EMEND is based on the findings of a study published in April 2005 in the Journal of Clinical Oncology (JCO) that enrolled 866 breast cancer patients, of whom 99.5 percent were women. The study compared a regimen including EMEND (EMEND in combination with ondansetron, a 5-HT3 receptor antagonist, and dexamethasone, a corticosteroid, on day 1 followed by EMEND on day 2 and 3) and a standard regimen (ondansetron and dexamethasone on day 1 followed by ondansetron on day 2 and 3).

Results from this study of breast cancer patients who received moderately emetogenic chemotherapy treatments, which are likely to cause nausea and vomiting, showed that a significantly higher proportion of patients treated with the regimen including EMEND in Cycle 1 reported a complete response (defined as no vomiting and no use of other therapies for nausea or vomiting) in the five days after initiation of chemotherapy compared to a standard regimen (51% vs. 42% , p=0.015). The difference between treatment groups was primarily driven by the "No Emesis Endpoint", a principal component of this composite primary endpoint. In addition, a higher proportion of patients receiving the regimen including EMEND in Cycle 1 had a complete response during the acute (0-24 hours) and delayed (25-120 hours) phases compared with patients receiving the standard regimen; however, the treatment group differences failed to reach statistical significance after multiplicity adjustments.

"Patients with cancer are not only facing a serious illness, they also face the possibility of distressing side effects such as nausea and vomiting from their chemotherapy, and breast cancer patients are particularly susceptible to these side effects," said Kelly Pendergrass, M.D., clinical investigator and medical oncologist at the Kansas City Cancer Center. "The good news is that, with this expanded indication, EMEND can now be used with other antiemetics in the wider population of patients receiving moderately emetogenic chemotherapy to help prevent these worrisome and challenging side effects before they occur."

The study also showed that more patients receiving EMEND reported minimal or no impact of nausea and vomiting on their daily life (64% vs. 56%). This difference between treatment groups was primarily driven by the "No Vomiting Domain" of this composite endpoint. Patients were permitted to continue into a multiple-cycle extension of the study for up to three additional cycles of chemotherapy. Results showed that antiemetic effectiveness for the patients receiving the regimen including EMEND was maintained during all cycles.

In Cycle 1, clinical adverse experiences were reported in approximately 73 percent of patients treated with the regimen including EMEND compared with approximately 75 percent of patients treated with the standard regimen. Adverse events reported at an equal to or higher incidence in Cycle 1 with the regimen including EMEND vs. standard regimen, respectively, were hair loss (24% vs. 22.2%), fatigue (21.9% vs. 21.5%), headache (16.4% vs. 16.4%), neutropenia (8.9% vs. 8.4%), dyspepsia (8.4% vs. 4.9%), stomatitis (5.3% vs. 4.4%), pharyngolaryngeal pain (3% vs. 2.3%), and hot flush (3% vs. 1.4%). The adverse experience profile was generally comparable to the highly emetogenic chemotherapy studies.

In the highly emetogenic studies, the most common side effects reported in Cycle 1 with the regimen including EMEND vs. standard regimen, respectively, were tiredness (17.8% vs. 11.8%), nausea (12.7% vs. 11.8%), hiccups (10.8% vs. 5.6%), constipation (10.3% vs. 12.2%), diarrhea (10.3% vs. 7.5%), and loss of appetite (10.1% vs. 9.5%).

About the study

This multicenter, randomized, double-blind, parallel-group study enrolled 866 breast cancer patients (99.5 percent women) who had never before undergone emetogenic chemotherapy. Patients were randomized to receive either the regimen including EMEND (N=438) or a standard regimen (N=428). Patients in the group who received the regimen including EMEND ranged from 25-78 years of age with a mean age of 53. Approximately 80 percent of the patients were White, eight percent Black, eight percent Asian, four percent Hispanic and less than one percent were other. Patients in the study received chemotherapy regimens that included cyclophosphamide 750-1500 mg/m2; or cyclophosphamide 500-1500 mg/m2 and doxorubicin ((less than or equal to 60 mg/m2) or epirubicin (less than or equal to 100 mg/m2). In this study, the most common combinations were cyclophosphamide plus doxorubicin (60.6%); and cyclophosphamide plus epirubicin plus fluorouracil (21.6%).