|[April 14, 2014]
FDA Approves Merck's GRASTEK® (Timothy Grass Pollen Allergen Extract) Sublingual Tablet as Immunotherapy to Treat Grass Pollen-Induced Allergic Rhinitis with or without Conjunctivitis in Children and Adults
WHITEHOUSE STATION, N.J. --(Business Wire)--
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 GRASTEK® (Timothy Grass Pollen Allergen Extract)
Tablet for Sublingual Use [2800 Bioequivalent Allergy Units (BAU)].
GRASTEK is an allergen extract indicated as immunotherapy for the
treatment of grass pollen-induced allergic rhinitis with or without
conjunctivitis confirmed by positive skin test or in vitro
testing for pollen-specific IgE antibodies for Timothy grass or
cross-reactive grass pollens. GRASTEK is approved for use in persons 5
through 65 years of age. GRASTEK is not indicated for the immediate
relief of allergic symptoms.
The prescribing information for GRASTEK includes a boxed warning
regarding severe allergic reactions. GRASTEK is contraindicated in
patients with severe, unstable or uncontrolled asthma; a history of any
severe systemic allergic reaction; a history of any severe local
reaction after taking any sublingual allergen immunotherapy; a history
of eosinophilic esophagitis; or hypersensitivity to any of the inactive
ingredients contained in the product.
"Every grass pollen season, many patients with moderate to severe
allergic rhinitis experience nasal and ocular allergy symptoms at their
worst while taking symptom-relieving medication," said Dr. David
Bernstein, professor of medicine and environmental health, Division of
Immunology, Allergy and Rheumatology, University of Cincinnati College
of Medicine. "These patients often have multiple sensitivities. Some of
these patients may be candidates for immunotherapy, but decline allergy
shots. With the FDA approval of GRASTEK, allergy specialists now have a
new sublingual approach to offer these patients for their grass
Symptoms of grass pollen-induced allergic rhinitis with or without
conjunctivitis may include sneezing, runny or itchy nose, stuffy or
congested nose, or itchy and watery eyes, and typically intensify during
the grass pollen season.
"The FDA approval of GRASTEK brings an important new sublingual tablet
for allergy specialists treating adults and children with allergic
rhinitis with or without conjunctivitis caused by Timothy or
cross-reactive grass pollens," said Dr. Sean Curtis, vice president,
Respiratory and Immunology, Merck Research Laboratories. "This important
milestone marks another opportunity for Merck to build on our
respiratory heritage with allergy specialists."
About Timothy grass allergy
Timothy grass is one of the most common grasses in the United States and
has been demonstrated to be cross-reactive with other grasses, including
sweet vernal, orchard (also known as cocksfoot), perennial rye, Kentucky
blue (also known as June grass), meadow fescue and redtop. Timing of the
grass pollen season varies regionally across the United States.
Dosing and administration of GRASTEK (Timothy Grass Pollen Allergen
The recommended dose of GRASTEK is one tablet daily to be placed under
the tongue, where it will dissolve.
The first dose of GRASTEK should be administered in a healthcare setting
under the supervision of a physician with experience in the diagnosis
and treatment of allergic diseases. The physician should observe the
patient for at least 30 minutes after receiving the first dose of
GRASTEK to monitor for signs or symptoms of a severe systemic or a
severe local allergic reaction. If the patient tolerates the first dose,
the patient may take subsequent doses at home. The physician should
prescribe auto-injectable epinephrine, and instruct and train the
patient on its appropriate use. Children must take GRASTEK under adult
Initiate GRASTEK at least 12 weeks before the expected onset of each
grass pollen season and continue treatment throughout the season. The
safety and efficacy of in-season initiation have not been established.
For sustained effectiveness for one grass pollen season after cessation
of treatment, GRASTEK may be taken daily for three consecutive years
(including the intervals between the grass pollen seasons). The safety
and efficacy of in-season initiation have not been established.
GRASTEK will be available in U.S. pharmacies in late April.
About the clinical study program for GRASTEK (Timothy Grass Pollen
The efficacy of GRASTEK was supported by two studies of approximately 24
weeks treatment duration over one grass season each in patients 5
through 65 years of age, and one 5-year grass pollen season study in
patients 18 through 65 years of age. In all three randomized,
double-blind, parallel-group, multi-center studies:
Patients had a history of grass pollen-induced allergic rhinitis with
or without conjunctivitis, and sensitivity to grass confirmed by
positive skin test or in vitro testing for pollen-specific IgE
antibodies for Timothy grass;
Patients with non-grass sensitivities were included as long as the
patients did not require treatment as a result of symptoms from those
non-grass allergies during the grass season;
GRASTEK or placebo was administered as a sublingual tablet and
initiated approximately 12 weeks before the start of the grass pollen
Patients in both arms of the study were allowed to take
symptom-relieving medications (including systemic and topical
antihistamines, and topical and oral corticosteroids) as needed;
Efficacy was established by self-reporting of rhinoconjunctivitis
daily symptom scores (DSS) and daily medication scores (DMS), the sums
of which were combined into the total combined scores (TCS);
Daily rhinoconjunctivitis symptoms included four nasal symptoms (runny
nose, stuffy nose, sneezing and itchy nose), and two ocular symptoms
(gritty/itchy eyes and watery eyes).
The FDA criteria for clinically relevant efficacy of allergen
immunotherapy is based on the TCS, which must have an average difference
relative to placebo of less than or equal to -15 percent, and the upper
bound of the 95 percent confidence interval (CI) must be less than or
equal to -10 percent.
First season efficacy in adults and children
One study compared GRASTEK to placebo in 1,501 patients 5 through 65
years of age, of whom approximately 25 percent had mild, intermittent
asthma and 85 percent were sensitized to other allergens in addition to
grass. Patients treated with GRASTEK had significant reduction f nasal
and ocular symptoms, and reduction in use of symptom-relieving allergy
medication, as measured by a decrease in the TCS for the entire grass
pollen season, compared to placebo; difference for GRASTEK (Timothy
Grass Pollen Allergen Extract) (n=629) relative to placebo (n=672) was
-23 percent (95% CI: -36.0%; -13.0%).
A second study compared GRASTEK to placebo in 344 patients 5 through 17
years of age, of whom 26 percent had mild, intermittent asthma and 89
percent were sensitized to other allergens in addition to grass.
Patients treated with GRASTEK had significant reduction of nasal and
ocular symptoms, and reduction in use of symptom-relieving allergy
medication, as measured by a decrease in the TCS for the entire grass
pollen season, compared to placebo; difference for GRASTEK (n=149)
relative to placebo (n=158) was -26 percent (95% CI: -38.2%; -10.1%).
In one 5-year study, 634 patients 18 through 65 years of age received
GRASTEK or placebo for three consecutive years and were then observed
for two years during which they did not receive study drug. Patients
treated with GRASTEK had a decrease in TCS throughout the grass pollen
season during the three years of active treatment. This effect was
sustained during the grass pollen season in the first year after
discontinuation of GRASTEK, but not in the second year.
TCS difference (GRASTEK relative to placebo) per year:
Year 1: -34% (95% CI: -42.0%;-26.3%); (n=568*)
Year 2: -41% (95% CI: -51.8%;-29.5%); (n=316*)
Year 3: -34%;(95% CI: -45.5%;-21.4%); (n=287*)
Post Treatment Year 1: -27% (95% CI: -39.9%;-12.4%); (n=257*)
*Number of patients in analysis in both treatment groups (GRASTEK and
About allergic rhinitis due to Timothy and cross-reactive grasses
It is estimated that approximately 7.5 million U.S. children and adults
ages 5 to 64 have been diagnosed with moderate to severe allergic
rhinitis and are sensitized to Timothy and cross-reactive grass pollens.
Selected safety information about GRASTEK (Timothy Grass Pollen
WARNING: SEVERE ALLERGIC REACTIONS
GRASTEK can cause life-threatening allergic reactions such as
anaphylaxis and severe laryngopharyngeal restriction. Do not administer
GRASTEK to patients with severe, unstable or uncontrolled asthma.
Observe patients in the office for at least 30 minutes following the
initial dose. Prescribe auto-injectable epinephrine, instruct and train
patients on its appropriate use, and instruct patients to seek immediate
medical care upon its use. GRASTEK may not be suitable for patients with
certain underlying medical conditions that may reduce their ability to
survive a serious allergic reaction. GRASTEK may not be suitable for
patients who may be unresponsive to epinephrine or inhaled
bronchodilators, such as those taking beta-blockers.
GRASTEK is contraindicated in patients with severe, unstable, or
uncontrolled asthma; a history of any severe systemic allergic reaction;
a history of any severe local reaction after taking sublingual allergen
immunotherapy; a history of eosinophilic esophagitis; or
hypersensitivity to any of the inactive ingredients (gelatin, mannitol
and sodium hydroxide) contained in the product.
GRASTEK can cause systemic allergic reactions including anaphylaxis
which may be life-threatening. In addition, GRASTEK can cause severe
local reactions, including laryngopharyngeal swelling, which can
compromise breathing and be life-threatening. Educate patients to
recognize the signs and symptoms of these allergic reactions and
instruct them to seek immediate medical care and discontinue therapy
should any of these occur. Allergic reactions may require treatment with
epinephrine. Prescribe auto-injectable epinephrine to patients receiving
GRASTEK. Instruct patients to recognize the signs and symptoms of a
severe allergic reaction, and in the proper use of emergency
auto-injectable epinephrine. Instruct patients to seek immediate medical
care upon use of auto-injectable epinephrine and to stop treatment with
GRASTEK. Review the epinephrine package insert for complete information.
Administer the initial dose of GRASTEK in a healthcare setting under the
supervision of a physician with experience in the diagnosis and
treatment of allergic diseases, and prepared to manage a
life-threatening systemic or local allergic reaction. Observe patients
in the office for at least 30 minutes following the initial dose of
GRASTEK can cause local reactions in the mouth or throat that could
compromise the upper airway. Consider discontinuation of GRASTEK in
patients who experience persistent and escalating adverse reactions in
the mouth or throat.
Eosinophilic esophagitis has been reported in association with
sublingual tablet immunotherapy. Discontinue GRASTEK (Timothy Grass
Pollen Allergen Extract) and consider a diagnosis of eosinophilic
esophagitis in patients who experience severe or persistent
gastro-esophageal symptoms including dysphagia or chest pain.
GRASTEK has not been studied in patients with moderate or severe asthma
or any patients who required daily medication to treat asthma. Withhold
immunotherapy with GRASTEK if the patient is experiencing an acute
GRASTEK has not been studied in patients who are receiving concomitant
allergen immunotherapy. Concomitant dosing with other allergen
immunotherapy may increase the likelihood of local or systemic adverse
reactions to either subcutaneous or sublingual allergen immunotherapy.
Stop treatment with GRASTEK to allow complete healing of the oral cavity
in patients with oral inflammation (e.g., oral lichen planus, mouth
ulcers or thrush) or oral wounds, such as those following oral surgery
or dental extraction.
The most common adverse reactions reported in clinical studies for
patients 18 through 65 years of age with Timothy grass pollen-induced
allergic rhinitis with or without conjunctivitis and treated with
GRASTEK vs. placebo included oral pruritus (26.7% vs. 3.5%), throat
irritation (22.6% vs. 2.8%), ear pruritus (12.5% vs. 1.1%) and mouth
edema (11.1% vs. 0.8%).
The most common adverse reactions for GRASTEK vs. placebo in clinical
studies for pediatric patients between 5 and 17 years of age with grass
pollen-induced allergic rhinitis with or without conjunctivitis included
oral pruritus (24.4% vs. 2.1%), throat irritation (21.3% vs. 2.5%), and
mouth edema (9.8% vs. 0.2%).
Because systemic and local adverse reactions with immunotherapy may be
poorly tolerated during pregnancy, GRASTEK should be used during
pregnancy only if clearly needed.
Find an allergy specialist
To find an allergy specialist, please visit the websites of the American
Academy of Allergy, Asthma, and Immunology (AAAAI); the American
College of Allergy, Asthma & Immunology (ACAAI); or the American
Academy of Otolaryngic Allergy (AAOA).
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well. Merck is known as MSD outside the United States and Canada.
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more information, visit www.merck.com
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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
Risks and uncertainties include but are not limited to, general industry
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rate and currency exchange rate fluctuations; the impact of
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including obtaining regulatory approval; Merck's ability to accurately
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for innovative products; and the exposure to litigation, including
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Merck undertakes no obligation to publicly update any forward-looking
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found in Merck's 2013 Annual Report on Form 10-K and the company's other
filings with the Securities and Exchange Commission (SEC (News - Alert)) available at
the SEC's Internet site (www.sec.gov).
GRASTEK® is a registered trademark of Merck
& Co., Inc., Whitehouse Station, N.J., USA.
Please see Prescribing Information, including Boxed Warning, for
GRASTEK (Timothy Grass Pollen Allergen Extract) Tablet for Sublingual
Use at http://www.merck.com/product/usa/pi_circulars/g/grastek/grastek_pi.pdf
and Medication Guide for GRASTEK at http://www.merck.com/product/usa/pi_circulars/g/grastek/grastek_mg.pdf.
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