First and Only Intravenous NK1
Receptor Antagonist Approved in the U.S. for Use in MEC
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
single-dose EMEND® (fosaprepitant dimeglumine) for injection,
Merck’s substance P/neurokinin-1 (NK1) receptor antagonist, in
combination with other antiemetic medicines, for the prevention of
delayed nausea and vomiting in adults receiving initial and repeat
courses of moderately emetogenic chemotherapy (MEC). EMEND has not
been studied for the treatment of established nausea and
vomiting.
The FDA approval is supported by data from a Phase 3 study that
showed single-dose EMEND for injection, combined with other
anti-vomiting medicines, provided greater protection from delayed
nausea and vomiting following administration of moderately
emetogenic chemotherapy versus an active control regimen. With this
approval, EMEND for injection is the first intravenous single-dose
NK1 receptor antagonist approved in the U.S. for both highly
emetogenic chemotherapy (HEC) as well as MEC.
EMEND for injection is contraindicated in patients who are
hypersensitive to any component of the product and in patients
taking pimozide.
“Despite significant advances in supportive care, nausea and
vomiting has remained a challenge for many cancer patients
undergoing moderately emetogenic chemotherapy – and has
historically required multi-day antiemetic therapy,” said Stuart
Green, vice president, clinical research, Merck Research
Laboratories. “Today’s approval of an expanded indication for EMEND
for injection means that physicians now have a new single-dose
intravenous option, combined with other anti-vomiting medicines,
for the prevention of delayed nausea and vomiting in these
patients.”
Data Supporting the FDA Approval
The FDA approval of this new indication was based in part on
findings from a randomized, parallel, double-blind, active
comparator-controlled study that evaluated EMEND (fosaprepitant
dimeglumine) for injection (150 mg) as a single intravenous
infusion in combination with ondansetron and dexamethasone
(referred to as the EMEND regimen) (n=502) compared with
ondansetron and dexamethasone alone (control regimen) (n=498) in
patients receiving MEC. The primary endpoint was complete response
(defined as no vomiting and no use of rescue therapy) in the
delayed phase (25 to 120 hours following initiation of
chemotherapy) of chemotherapy-induced nausea and vomiting. A 78.9
percent complete response rate was observed with the EMEND regimen
compared to 68.5 percent with the control regimen (p<0.001). The
results of this trial were presented at the 2015 annual meeting of
the American Society of Clinical Oncology, and have now been
published in the journal Annals of Oncology.
The most common adverse reactions reported in the EMEND regimen
versus control regimen were fatigue (15% vs 13%), diarrhea (13% vs
11%), neutropenia (8% vs 7%), asthenia (4% vs 3%), anemia (3% vs
2%), peripheral neuropathy (3% vs 2%), leukopenia (2% vs 1%),
dyspepsia (2% vs 1%), urinary tract infection (2% vs 1%), and pain
in extremity (2% vs 1%).
About EMEND (fosaprepitant dimeglumine) for Injection
EMEND for injection is an intravenous prodrug of the oral
formulation of EMEND® (aprepitant). When EMEND for injection is
administered, fosaprepitant is rapidly converted in the body to
aprepitant. 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 for injection, 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 chemotherapy (HEC) including
high-dose cisplatin and for the prevention of delayed nausea and
vomiting associated with initial and repeat courses of moderately
emetogenic cancer chemotherapy (MEC).
EMEND has not been studied for the treatment of established
nausea and vomiting.
Selected Important Safety Information for EMEND
(fosaprepitant dimeglumine) for Injection
EMEND is contraindicated in patients who are hypersensitive to
any component of the product. Hypersensitivity reactions including
anaphylactic reactions, flushing, erythema, and dyspnea have been
reported. If symptoms occur, discontinue the infusion and
administer appropriate medical therapy. Do not reinitiate the
infusion in patients who experience these symptoms during
first-time use.
EMEND is contraindicated in patients taking pimozide. Inhibition
of CYP3A4 by aprepitant, the active drug, 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.
Fosaprepitant, a prodrug of aprepitant, is a weak inhibitor of
CYP3A4, and aprepitant is a substrate, inhibitor, and 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 (eg,
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 (eg,
rifampin) may result in a reduction in aprepitant plasma
concentrations and decreased efficacy of EMEND.
Reduce the dose of the co-administered corticosteroid on Days 1
and 2 for patients receiving HEC and on Day 1 for patients
receiving MEC as follows: oral dexamethasone by approximately 50%;
oral methylprednisolone by approximately 50%; and intravenous
methylprednisolone by approximately 25%.
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 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 EMEND 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. Advise patients to use effective alternative or backup
methods of contraception during treatment with EMEND (fosaprepitant
dimeglumine) and for 1 month following administration of EMEND.
In the MEC study, the most common adverse reactions reported in
at least 2% of patients treated with the EMEND regimen and at a
greater incidence than the control regimen were: fatigue (15% EMEND
regimen vs 13% control regimen), diarrhea (13% vs 11%), neutropenia
(8% vs 7%), asthenia (4% vs 3%), anemia (3% vs 2%), peripheral
neuropathy (3% vs 2%), leukopenia (2% vs 1%), dyspepsia (2% vs 1%),
urinary tract infection (2% vs 1%), and pain in extremity (2% vs
1%). In the HEC study, the safety profile was generally similar to
that seen in the MEC study with fosaprepitant and prior HEC studies
with aprepitant.
In the MEC study, infusion-site reactions were reported in 2.2%
of patients treated with the EMEND regimen compared to 0.6% of
patients treated with the control regimen, including infusion-site
pain (1.2% EMEND regimen vs 0.4% control regimen), injection-site
irritation (0.2% vs 0.0%), vessel puncture-site pain (0.2% vs
0.0%), and infusion-site thrombophlebitis (0.6% vs 0.0%). In the
HEC study, which compared fosaprepitant to aprepitant,
infusion-site reactions occurred at a higher incidence in the
fosaprepitant group (3.0%) than in the aprepitant group (0.5%). The
following additional infusion-site reactions occurred in the HEC
study and were not reported in the MEC study: infusion-site
erythema (0.5% for fosaprepitant vs 0.1% for aprepitant),
infusion-site pruritus (0.3% vs 0.0%), and infusion-site induration
(0.2% vs 0.1%).
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 health care 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 health care through far-reaching policies, programs and
partnerships. For more information, visit www.merck.com and connect
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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
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industry conditions and competition; general economic factors,
including interest rate and currency exchange rate fluctuations;
the impact of pharmaceutical industry regulation and health care
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The company undertakes no obligation to publicly update any
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Internet site (www.sec.gov).
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.
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