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, Facebook and YouTube.
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.
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