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Merck announces data from investigational Phase 3 study on EMEND® (aprepitant) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in children undergoing emetogenic chemotherapy

Posted: 1 July 2014 | | No comments yet

Merck planning regulatory submissions in the U.S. for EMEND® in pediatric setting including new suspension formulation in second half of 2014…

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Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced results from a global, investigational Phase 3 study to evaluate the safety and efficacy of EMEND® (aprepitant) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in pediatric cancer patients, aged 6 months to 17 years. In this study in pediatric cancer patients undergoing very highly, highly, or moderately emetogenic (vomit-inducing) chemotherapy, the use of the EMEND regimen for CINV prevention was significantly more effective than a control regimen in achieving Complete Response, defined as no vomiting or retching and no use of rescue medication for nausea and vomiting, in all phases of CINV (acute, delayed, and overall). These new data were presented in an oral session at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Annual International Symposium on Supportive Care in Cancer (Abstract #0286) by Dr. Hyoung Jin Kang, M.D., Ph.D., lead investigator and associate professor, Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

“Nausea and vomiting are common complications of cancer chemotherapy and can be particularly distressful and debilitating to pediatric cancer patients,” said Dr. Stuart Green, vice president, clinical research, Merck Research Laboratories. “In this large pediatric study, adding EMEND to a standard regimen for prevention of CINV resulted in significant reduction of emetic events.”

Based on these data, Merck plans worldwide regulatory submissions for EMEND (aprepitant), beginning in the United States, for use in the prevention of CINV in pediatric and adolescent cancer patients (ages 6 months to 17 years). In the United States, Merck plans to submit a New Drug Application (NDA) for a new pediatric formulation (powder for suspension) and a supplemental NDA for use of the current formulation (capsules). Both filings are planned for the second half of 2014.

EMEND, a Substance P/Neurokinin-1 (NK1) receptor antagonist approved for use in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin; and for prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. EMEND has not been studied for treatment of established nausea and vomiting. Chronic continuous administration of EMEND is not recommended. Safety and efficacy of EMEND in pediatric patients have not been established.

Efficacy and Safety Findings for Investigational, Phase 3 CINV Prevention Study of EMEND in Pediatric Patients

The Phase 3 randomized, double-blind, active-comparator study of 302 participants evaluated EMEND for prevention of CINV in children (ages 6 months to 17 years of age). In the study, patients receiving emetogenic chemotherapy were randomly assigned to receive an EMEND plus ondansetron regimen (n=152) or a control regimen (placebo plus ondansetron) (n=150). The EMEND regimen included either EMEND capsules or an investigational powder for suspension formulation of aprepitant dosed based on weight. Ondansetron dosing was based on the approved pediatric dose (as per the local label). The primary endpoint of the study was complete response (no vomiting, no retching, and no use of rescue medication for nausea and vomiting) in the delayed phase (25 to 120 hours following initiation of chemotherapy). The secondary endpoints were complete response in the acute phase (0 to 24 hours) and overall phase (0-120 hours), and no vomiting in the overall phase. In both groups, the first dose of EMEND (plus ondansetron) was administered on day 1 of chemotherapy, then subsequently (without ondansetron) later on days 2 and 3. Dexamethasone could be administered intravenously per investigator discretion (the dose was based on weight). Administration of dexamethasone was similar in patients receiving the EMEND regimen and the control regimen (44 vs. 42 patients, respectively).

EMEND Regimen Increased Complete Response in Days 2 through 5 (primary endpoint)

In the study, 51 percent of patients receiving the EMEND (aprepitant) regimen achieved the primary endpoint of complete response in the delayed phase of CINV, versus 26 percent of those in the control group (p <0.0001). For the secondary endpoints, 66 percent of patients receiving the EMEND regimen achieved a complete response in the acute phase of CINV, versus 52 percent of those receiving the control regimen (p = 0.0135). In addition, complete response in the overall phase was higher in patients receiving the EMEND regimen versus the control regimen (40% vs. 20%, p =0.0002). No vomiting in the overall phase was observed in 47 percent vs. 21 percent of patients receiving the EMEND regimen compared to the control regimen, respectively (p <0.0001).

Overall, 79 percent of patients receiving the EMEND regimen and 77 percent receiving the control regimen experienced one or more adverse events. The most common adverse events (across all grades) with the EMEND regimen compared to the control regimen included anemia (17% vs. 25%), febrile neutropenia (16% for both groups), vomiting (15% for both groups), neutropenia (14% vs. 12%), thrombocytopenia (10% vs. 11%), decreased neutrophil count (9% vs. 13%), nausea (9% vs. 11%), and a decreased platelet count (8% vs. 10%). Treatment-related adverse events were observed in 3 percent (5/152) of patients receiving the EMEND regimen and in 2 percent (3/150) of patients receiving the control regimen. Serious treatment-related adverse events were observed in 1 percent (2/152) of patients on an EMEND regimen and in 0 percent (0/150) of patients receiving the control regimen.

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