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September 2, 2015 7:00 am ET

Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that the U.S. Food and Drug Administration (FDA) has
approved a supplemental New Drug Application (sNDA) for EMEND^®
(aprepitant) capsules, a substance P/neurokinin 1 (NK1) receptor
antagonist. With this expanded indication, EMEND capsules are now
approved for use in combination with other antiemetic agents in patients
12 years of age and older and patients less than 12 years who weigh at
least 30 kg (approximately 66 pounds) for the prevention of acute and
delayed nausea and vomiting associated with initial and repeat courses
of highly emetogenic cancer chemotherapy (HEC) including high-dose
cisplatin, as well as for the prevention of nausea and vomiting
associated with initial and repeat courses of moderately emetogenic
cancer chemotherapy (MEC). EMEND has not been studied for treatment of
established nausea and vomiting. Chronic continuous administration of
EMEND is not recommended because it has not been studied, and because
the drug interaction profile may change during chronic continuous use.

With this approval, EMEND is the first and only NK1 receptor antagonist
to be approved for the prevention of acute and delayed phases of
chemotherapy-induced nausea and vomiting (CINV) in patients 12 to 17
years of age and patients less than 12 years who weigh at least 30 kg
receiving HEC or MEC. The approval was supported by data from a pivotal
Phase 3 study that showed adding EMEND to a standard regimen for
prevention of CINV in HEC or MEC regimens resulted in a reduction of
emetic events.

EMEND is contraindicated in patients with any known sensitivity to any
component of this drug. EMEND is also contraindicated for patients
taking pimozide.

There is no commercially available dosage formulation of EMEND
appropriate for patients less than 12 years of age and weighing less
than 30 kg. Therefore, EMEND is indicated for the prevention of nausea
and vomiting associated with HEC or MEC in patients 12 years of age and
older and patients less than 12 years of age who weigh at least 30 kg.

Data Supporting the Expanded FDA Approval

The FDA approval of this expanded indication for EMEND (aprepitant) was
based in part on findings from a randomized, double-blind,
active-comparator-controlled clinical study that assessed EMEND in
combination with ondansetron (EMEND regimen) compared to ondansetron
alone (control regimen) for the prevention of CINV in patients 12 to 17
years of age and patients less than 12 years of age who weighed at least
30 kg (n=63 and 69, respectively) receiving HEC or MEC. Intravenous
dexamethasone was permitted at the discretion of the physician. The
primary endpoint was complete response (no vomiting, retching and no use
of rescue medication) in the delayed phase (25 to 120 hours following
initiation of chemotherapy). Other pre-specified endpoints included:
complete response in the acute phase (0 to 24 hours following initiation
of chemotherapy), complete response in the overall phase (up to 120
hours following initiation of chemotherapy), and safety and
tolerability. For the population aged 12 to 17 years and patients less
than 12 years who weighed at least 30 kg (n=132), data included in the
label show that in the delayed phase, a 49.2 percent (n=31/63) complete
response rate was observed in the EMEND regimen compared to 18.8 percent
(n=13/69) in the control regimen; in the acute phase, a 55.6 percent
(n=35/63) complete response was observed in the EMEND regimen compared
to 37.7 percent (n=26/69) in the control regimen; and, in the overall
phase, a 34.9 percent (n=22/63) complete response was observed in the
EMEND regimen compared to 13.0 percent (n=9/69) in the control regimen.

The most common adverse reactions reported in pooled studies of 352
pediatric patients receiving HEC or MEC treated with the EMEND regimen
(versus the control regimen) were neutropenia (13% vs 11%), headache (9%
vs 5%), diarrhea (6% vs 5%), decreased appetite (5% vs 4%), cough (5% vs
3%), fatigue (5% vs 2%), hemoglobin decreased (5% vs 4%), dizziness (5%
vs 1%), and hiccups (4% vs 1%).

“The FDA approval of this expanded indication for EMEND is the result of
our commitment to fully realizing the potential of our therapies to help
as many patients as possible,” said Stuart Green, vice president,
clinical research, Merck Research Laboratories. “Historically,
significant improvements in pediatric medicine have been slow due to
many challenges such as clinical trial size. However, at Merck, these
obstacles have invigorated our efforts to bring forward a new option for
these patients.”

About EMEND

EMEND^® (aprepitant) is a selective high-affinity
antagonist of human substance P/neurokinin 1 (NK₁) receptors.
Aprepitant has little or no affinity for serotonin (5-HT₃),
dopamine, and corticosteroid receptors, the targets of existing
therapies for chemotherapy-induced nausea and vomiting (CINV).

EMEND (aprepitant) is indicated in combination with other
antiemetic agents in patients 12 years of age and older and patients
less than 12 years of age who weigh at least 30 kg for the prevention of
acute and delayed nausea and vomiting associated with initial and repeat
courses of HEC including high-dose cisplatin as well as nausea and
vomiting associated with initial and repeat courses of MEC. EMEND has
not been studied for the treatment of established nausea and vomiting.
Chronic continuous administration of EMEND is not recommended because it
has not been studied, and because the drug interaction profile may
change during chronic continuous use.

Selected Safety Information

EMEND is contraindicated in patients who are hypersensitive to any
component of the product. Hypersensitivity reactions including
anaphylactic reactions have been reported.

EMEND is contraindicated in patients taking pimozide. Inhibition of
CYP3A4 by aprepitant could result in elevated plasma concentrations of
this drug which is a CYP3A4 substrate, potentially causing serious or
life-threatening reactions, such as QT prolongation.

Aprepitant is a substrate, a weak-to-moderate (dose-dependent)
inhibitor, and an inducer of CYP3A4. Use of EMEND with other drugs that
are CYP3A4 substrates, may result in increased plasma concentrations of
the concomitant drug. Use of EMEND with strong or moderate CYP3A4
inhibitors (e.g., ketoconazole, diltiazem) may increase plasma
concentrations of aprepitant and result in an increased risk of adverse
reactions related to EMEND. Use of EMEND with strong CYP3A4 inducers
(e.g., rifampin) may result in a reduction in aprepitant plasma
concentrations and decreased efficacy of EMEND.

Co-administration with oral dexamethasone: reduce the dose of oral
dexamethasone by approximately 50%. Co-administration with intravenous
methylprednisolone: reduce the dose of intravenous methylprednisolone by
approximately 25%. Co-administration with oral methylprednisolone:
reduce the dose of oral methylprednisolone by approximately 50%.

Monitor patients taking vinblastine, vincristine, or ifosfamide or other
chemotherapeutic agents that are metabolized by CYP3A4 for
chemotherapeutic-related adverse reactions. No dosage adjustments are
needed when etoposide, vinorelbine, paclitaxel, or docetaxel are
administered.

Coadministration of EMEND (aprepitant) 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, monitor the INR in the 2-week period,
particularly at 7 to 10 days, following initiation of the 3-day regimen
of EMEND (aprepitant) with each chemotherapy cycle.

Upon coadministration with EMEND, the efficacy of hormonal
contraceptives (including birth control pills, skin patches, implants,
and certain IUDs) may be reduced during administration of and for 28
days following the last dose of EMEND. Advise patients to use
alternative or back-up methods of contraception during treatment with
EMEND and for 1 month following the last dose of EMEND.

In HEC and MEC clinical studies with adults, EMEND in combination with
ondansetron and dexamethasone (EMEND regimen) was compared with
ondansetron and dexamethasone alone (standard therapy). The most common
adverse reactions reported in at least 3% of patients treated with the
EMEND regimen and at a greater incidence than standard therapy, were:
fatigue (13% EMEND regimen vs 12% standard therapy), diarrhea (9% vs 8%
), asthenia (7% vs 6%), dyspepsia (7% vs 5%), abdominal pain (6% vs 5%),
hiccups (5% vs 3%), decreased white blood cell count (4% vs 3%),
dehydration (3% vs 2%), and increased alanine aminotransferase (3% vs
2%).

In HEC and MEC clinical studies in pediatric patients, EMEND in
combination with ondansetron with or without dexamethasone (EMEND
regimen) was compared to ondansetron with or without dexamethasone
(control regimen). The most common adverse reactions reported in at
least 3% of patients treated with the EMEND regimen and at a greater
incidence than the control regimen, were: neutropenia (13% EMEND regimen
vs 11% control regimen), headache (9% vs 5%), diarrhea (6% vs 5%),
decreased appetite (5% vs 4%), cough (5% vs 3%), fatigue (5% vs 2%),
decreased hemoglobin (5% vs 4%), dizziness (5% vs 1%), and hiccups (4%
vs 1%).

Dosing of EMEND Capsules

EMEND is administered as part of a 3-day regimen for the prevention of
nausea and vomiting associated with HEC or MEC in adults and pediatric
patients 12 years of age and older and patients less than 12 years of
age who weigh at least 30 kg, who can swallow oral capsules. The
recommended dosage of EMEND is a 125-mg capsule given on Day 1 of
chemotherapy, followed by 80-mg capsules given on each of Days 2-3. In
adults, the regimen includes coadministration with dexamethasone and a
5-HT₃ antagonist. In pediatric patients receiving HEC or MEC
who are 12 years and older or weighing at least 30 kg, and who can
swallow oral capsules, the regimen includes coadministration of a 5-HT₃
antagonist and may include coadministration of a corticosteroid such as
dexamethasone. Please refer to the package insert for EMEND (aprepitant)
for detailed dosing instructions regarding the coadministration of a
corticosteroid. Please also refer to the package insert of the selected
5-HT₃ antagonist for the recommended dosage of the 5-HT₃
antagonist.

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,
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Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the
“company”) includes “forward-looking statements” within the meaning of
the safe harbor provisions of the U.S. Private Securities Litigation
Reform Act of 1995. These statements are based upon the current beliefs
and expectations of the company’s management and are subject to
significant risks and uncertainties. There can be no guarantees with
respect to pipeline products that the products will receive the
necessary regulatory approvals or that they will prove to be
commercially successful. 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 health care legislation in the
United States and internationally; global trends toward health care cost
containment; technological advances, new products and patents attained
by competitors; challenges inherent in new product development,
including obtaining regulatory approval; the company’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 the company’s patents
and other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory actions.

The company 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 the company’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.

Merck
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