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)
at
http://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 at
http://www.merck.com/product/usa/pi_circulars/e/emend_iv/emend_iv_ppi.pdf.
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