FDA Approves Merck’s Single-Dose EMEND® (fosaprepitant dimeglumine) for Injection, in Combination with Other Antiemetic Agents, for the Prevention of Delayed Nausea and Vomiting in Adults Receiving Moderately Emetogenic Chemotherapy (MEC)
February 4, 2016 8:00 am ET
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.
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“company”) includes “forward-looking statements” within the meaning of
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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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