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Emend Approved for use with Moderately Emetogenic Chemotherapy

FDA Approves Emend (aprepitant), in Combination with Other Antiemetics, for the Prevention of Nausea and Vomiting in Cancer Patients Undergoing Moderately Emetogenic Chemotherapy

WHITEHOUSE STATION, N.J., January 11, 2006 -- Merck & Co., Inc. announced today that the Food and Drug Administration (FDA) has approved Emend (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%).

Dosing for the regimen including Emend was Emend 125 mg orally one hour before chemotherapy, ondansetron 8 mg orally 30-60 minutes before chemotherapy followed by ondansetron 8 mg orally eight hours after the first ondansetron dose, and dexamethasone 12 mg orally 30 minutes before chemotherapy (dose chosen to account for drug interactions) on day 1 and Emend 80 mg once daily in the morning on days 2-3. Dosing for the standard regimen was ondansetron 8 mg 30-60 minutes before chemotherapy, dexamethasone 20 mg 30 minutes before chemotherapy and ondansetron 8 mg eight hours after the first ondansetron dose on day 1 and ondansetron 8 mg every 12 hours on days 2-3. Patients reported incidences of nausea, vomiting and use of other medications for nausea or vomiting in a diary for five days.

Important information about Emend

Emend is only used to help prevent nausea and vomiting caused by chemotherapy. It is not used to get rid of nausea and vomiting after they start.

Patients should tell their doctor about all other medicines they are taking, if they are pregnant or plan to become pregnant, or if they have liver problems. Patients should not take Emend with Orap (pimozide), Seldane (terfenadine), Hismanal (astemizole) or Propulsid (cisapride) as Emend may cause serious or life-threatening problems if taken with these medicines. Emend may also affect some medicines, including chemotherapy, causing them to work differently in the body. Women who use birth control medicines during treatment with Emend and for up to one month after using Emend should also use a backup method of contraception to avoid pregnancy.

Source: Merck & Co., Inc.

Posted: January 2006


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