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

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June 29, 2015 7:30 am ET

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
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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 at
http://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.

Merck
Media:
Doris Li, 908-740-1903
or
An Phan, 908-255-6325
or
Investor:
Joseph Romanelli, 908-740-1986
or
Justin Holko, 908-740-1879

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