From #Merck:

Merck Announces Phase 3 Study of Single-Dose EMEND® (fosaprepitant dimeglumine) for Injection Regimen Met Primary Endpoint in Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy

Monday, June 29, 2015 8:30 am EDT

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KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced results from a Phase 3 study investigating the safety and efficacy of single-dose EMEND^® (fosaprepitant dimeglumine) for Injection, Merck’s substance P/neurokinin (NK-1) receptor antagonist, in combination with other anti-vomiting medicines, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adult cancer patients receiving moderately emetogenic (vomit-inducing) chemotherapy (MEC). In the study, the first to evaluate an intravenous NK-1 receptor antagonist for the prevention of CINV associated with MEC, the single-dose EMEND for Injection regimen provided greater protection from nausea and vomiting following administration of chemotherapy versus an active control of placebo with other anti-vomiting medicines. These data were presented in an oral session at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Annual Meeting on Supportive Care in Cancer (Abstract #27-02-O) in Copenhagen (June 25-27, 2015).

“The results from this important Phase 3 trial are very encouraging as they are the first study to evaluate EMEND for Injection in a combination regimen for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy – and show the potential to use a single day antiemetic regimen,” said Dr. Bernardo L. Rapoport, principal investigator for the study and chief medical oncologist, Medical Oncology Centre of Rosebank, Johannesburg, South Africa.

"Nausea and vomiting remain a significant burden for patients receiving chemotherapy and we look forward to submitting these data for EMEND for Injection to the U.S. Food and Drug Administration,” said Stuart Green, vice president, clinical research, Merck Research Laboratories. “This study builds on our decade of research for EMEND and Merck’s overall commitment to help people with cancer.”

EMEND for Injection, 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 (HEC) chemotherapy, including high-dose cisplatin; and for prevention of nausea and vomiting associated with initial and repeat courses of MEC. EMEND has not been studied for treatment of established nausea and vomiting. Chronic continuous administration of EMEND is not recommended.

In the U.S., the single-dose regimen of EMEND for Injection is approved for use associated with HEC. Merck plans to submit these recent data to the Food and Drug Administration in the second half of 2015 to seek approval for a regimen containing single-dose EMEND for Injection for the prevention of CINV associated with MEC.

About Phase 3 Study for Single-Dose EMEND for Injection in MEC

In this global randomized, Phase 3, double-blind study, more than 1,000 patients receiving MEC were randomly assigned to receive either single-dose EMEND for Injection (150 mg) in combination with ondansetron capsules (16 mg) and dexamethasone capsules (12 mg) (n=504) on day one (followed by oral placebo for ondansetron on days two and three) or an active control regimen consisting of placebo (saline IV) in combination with ondansetron (16 mg) and dexamethasone (20 mg) (n=497) on day one (followed by 8 mg ondansetron on days two and three). The primary endpoint of the study was complete response (CR) (as measured by no vomiting and no use of rescue medication for nausea or vomiting) in the delayed phase (25 to 120 hours following initiation of chemotherapy). The secondary endpoints were CR after the first dose of chemotherapy in the acute phase (0 to 24 hours) and in the overall phase (0-120 hours), as well as no vomiting in the overall phase.

Single-Dose EMEND for Injection Regimen Achieved Superior Control of CINV

For the primary study endpoint, EMEND for Injection regimen provided higher incidence of CR in days 2 through 5 – with CR observed in 78.9 percent of patients receiving the EMEND for Injection regimen versus 68.5 percent in the active control group (p <0.001). For the secondary endpoints, in the acute phase, CR was observed in 93.2 percent of patients receiving the EMEND for Injection regimen versus 91 percent in the active control group (p = 0.184). In the overall phase, the incidence of CR was observed in 77.1 percent of patients receiving the EMEND for Injection regimen versus 66.9 percent in the active control group (p <0.001). Additionally, a significantly greater proportion of patients receiving the EMEND for Injection regimen experienced no vomiting in the overall phase (82.7 percent with EMEND vs 72.9 percent in the active control group) and delayed phase (83.9 percent with EMEND vs 75.1 percent in the active control group) (both p <0.001) – with a favorable trend in the acute phase (94.8 percent with EMEND vs 92 percent in the active control group).

The most common adverse events (across all grades) in the EMEND for Injection regimen and active control group included fatigue (15.1 percent and 12.9 percent), diarrhea (12.7 percent and 11.3 percent), and constipation (9.3 percent and 10.5 percent). Treatment-related adverse events were observed in 8.5 percent of patients receiving the EMEND for Injection regimen and in 9.1 percent of patients in the active control group. Serious treatment-related adverse events were observed in 0.2 percent of patients receiving the EMEND for Injection regimen and in 0.4 percent of patients in the active control group.

Selected Important Safety Information for EMEND (fosaprepitant dimeglumine) For Injection

EMEND for Injection is contraindicated in patients who are hypersensitive to EMEND for Injection, aprepitant, polysorbate 80, or any other components of the product. Known hypersensitivity reactions include flushing, erythema, dyspnea, and anaphylactic reactions.

Aprepitant, when administered orally, is a moderate cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitor. Because fosaprepitant is rapidly converted to aprepitant, neither drug should be used concurrently with pimozide or cisapride. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions.

EMEND for Injection should be used with caution in patients receiving concomitant medications, including chemotherapy agents that are primarily metabolized through CYP3A4. Inhibition of CYP3A4 by EMEND for Injection could result in elevated plasma concentrations of these concomitant medications. Conversely, when EMEND for Injection is used concomitantly with another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated. When EMEND for Injection is used concomitantly with medications that induce CYP3A4 activity, aprepitant plasma concentrations could be reduced, and this may result in decreased efficacy of aprepitant.

Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine. In clinical studies, EMEND was administered commonly with etoposide, vinorelbine, or paclitaxel. The doses of these agents were not adjusted to account for potential drug interactions. In separate pharmacokinetic studies, EMEND did not influence the pharmacokinetics of docetaxel or vinorelbine.

Because a small number of patients in clinical studies received the CYP3A4 substrates vinblastine, vincristine, or ifosfamide, particular caution and careful monitoring are advised in patients receiving these agents or other chemotherapy agents metabolized primarily by CYP3A4 that were not studied.

There have been isolated reports of immediate hypersensitivity reactions, including flushing, erythema, dyspnea, and anaphylaxis, during infusion of fosaprepitant. These hypersensitivity reactions have generally responded to discontinuation of the infusion and administration of appropriate therapy. It is not recommended to reinitiate the infusion in patients who have experienced these symptoms during first-time use.

Coadministration of EMEND for Injection with warfarin (a CYP2C9 substrate) may result in a clinically significant decrease in international normalized ratio (INR) of prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of EMEND for Injection with each chemotherapy cycle.

The efficacy of hormonal contraceptives (including birth control pills, skin patches, implants, and certain IUDs) may be reduced during coadministration with and for 28 days after the last dose of EMEND for Injection. Alternative or backup methods of contraception should be used during treatment with and for 1 month after the last dose of EMEND for Injection.

Chronic continuous use of EMEND for Injection for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during chronic continuous use.

In clinical trials of EMEND in patients receiving HEC, the most common adverse events reported at a frequency greater than with standard therapy, and at an incidence of 1% or greater, were hiccups (4.6% EMEND vs 2.9% standard therapy), asthenia/fatigue (2.9% vs 1.6%), increased ALT (2.8% vs 1.5%), increased AST (1.1% vs 0.9%), constipation (2.2% vs 2.0%), dyspepsia (1.5% vs 0.7%), diarrhea (1.1% vs 0.9%), headache (2.2% vs 1.8%), and anorexia (2.0% vs 0.5%).

In a clinical trial evaluating safety of the 1-day regimen of EMEND for Injection compared with the 3-day regimen of EMEND, the safety profile was generally similar to that seen in prior HEC studies with aprepitant. However, infusion-site reactions occurred at a higher incidence in patients who received fosaprepitant (3.0%) than in those who received aprepitant (0.5%). Those infusion-site reactions included infusion-site erythema, infusion-site pruritus, infusion-site pain, infusion-site induration, and infusion-site thrombophlebitis.

About Chemotherapy Induced Nausea and Vomiting (CINV)

Chemotherapy Induced Nausea and Vomiting (CINV) is a common side effect of chemotherapy caused by injured stomach cells that start the process of nausea and vomiting and can directly activate the area of the brain responsible for producing nausea and vomiting. The two main types of CINV are acute and delayed. Acute happens within the first 24 hours of receiving chemotherapy. Delayed happens from day 2 to day 5 after chemotherapy. The amount and timing of CINV can vary. Some chemotherapies cause acute nausea and vomiting. Others cause acute nausea and vomiting followed by another period of delayed nausea and vomiting.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology, and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

Today’s Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include, but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation in the United States and internationally; global trends toward healthcare cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2014 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Please see Prescribing Information for EMEND (aprepitant) athttp://www.merck.com/product/usa/pi_circulars/e/emend/emend_pi.pdf and Patient Information for EMEND (aprepitant) at http://www.merck.com/product/usa/pi_circulars/e/emend/emend_ppi.pdf

Please see Prescribing Information for EMEND (fosaprepitant dimeglumine) for Injection athttp://www.merck.com/product/usa/pi_circulars/e/emend_iv/emend_iv_pi.pdf and Patient Information for EMEND (fosaprepitant dimeglumine) for Injection athttp://www.merck.com/product/usa/pi_circulars/e/emend_iv/emend_iv_ppi.pdf.