FDA Approves Merck’s RAGWITEK™ (Short Ragweed Pollen Allergen Extract) Sublingual Tablet as Immunotherapy to Treat Short Ragweed Pollen-Induced Allergic Rhinitis with or without Conjunctivitis in Adults
April 17, 2014 5:22 pm ET
RAGWITEK is the First and Only FDA Approved Sublingual Allergen Immunotherapy Tablet Indicated for the Treatment of Short Ragweed Pollen Allergies
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 RAGWITEK™ (Short Ragweed Pollen Allergen Extract) Tablet for
Sublingual Use (12 Amb a 1-U). RAGWITEK is an allergen extract indicated
as immunotherapy for the treatment of short ragweed pollen-induced
allergic rhinitis with or without conjunctivitis confirmed by positive
skin test or in vitro testing for pollen-specific IgE antibodies
for short ragweed pollen. RAGWITEK is approved for use in adults 18
through 65 years of age. RAGWITEK is not indicated for the immediate
relief of allergic symptoms.
The prescribing information for RAGWITEK includes a boxed warning
regarding severe allergic reactions. RAGWITEK 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.
“RAGWITEK provides a new sublingual approach to allergen immunotherapy
for adult patients suffering from moderate to severe ragweed pollen
allergies who have declined allergy shots,” said Dr. David Skoner,
director, Division of Allergy and Immunology, Allegheny Health Network,
and a clinical investigator in Merck’s sublingual allergen immunotherapy
tablet program. “While there are regional variations, ragweed season
typically starts in mid-August across the United States. During the
season, many patients with moderate to severe allergic rhinitis
experience nasal and ocular allergy symptoms at their worst while taking
symptom-relieving medication. These patients often have multiple
sensitivities. To help prepare for the upcoming ragweed season, I would
encourage patients diagnosed with ragweed pollen allergies to make an
appointment now with an allergy specialist to discuss options.”
Symptoms of short ragweed pollen-induced allergic rhinitis with or
without conjunctivitis may include sneezing, a runny or itchy nose,
stuffy or congested nose, or itchy and watery eyes, and typically
intensify during the ragweed pollen season.
“The FDA approval of RAGWITEK brings an important new option for allergy
specialists treating adults with allergic rhinitis with or without
conjunctivitis caused by short ragweed pollen,” said Dr. Sean Curtis,
vice president, Respiratory and Immunology, Merck Research Laboratories.
“Merck is proud to add this second sublingual allergen immunotherapy
tablet to our respiratory portfolio.”
About short ragweed pollen allergy
While regional variation exists, in many areas of the United States
ragweed pollen season occurs from August to November. Ragweed pollen
levels usually peak in mid-September in many parts of the country.
Dosing and administration of RAGWITEK (Short Ragweed Pollen Allergen
The recommended dose of RAGWITEK is one tablet daily to be placed under
the tongue, where it will dissolve.
The first dose of RAGWITEK 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 RAGWITEK 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.
Initiate RAGWITEK at least 12 weeks before the expected onset of ragweed
pollen season and continue throughout the season. The safety and
efficacy of initiating treatment in season have not been established.
RAGWITEK will be available in U.S. pharmacies by the end of April.
About the clinical study program for RAGWITEK (Short Ragweed Pollen
The efficacy of RAGWITEK was supported by two Phase 3 clinical studies
over a single ragweed pollen season in patients 18 through 50 years of
age. In both randomized, double-blind, parallel group, multi-center
Patients had a history of short ragweed pollen-induced allergic
rhinitis with or without conjunctivitis, and sensitivity to short
ragweed confirmed by positive skin test or in vitro testing for
pollen-specific IgE antibodies for short ragweed;
Patients with non-ragweed sensitivities were included as long as the
patients did not require treatment as a result of symptoms from those
non-ragweed allergies during the ragweed season;
RAGWITEK or placebo was administered as a sublingual tablet and
initiated approximately 12 weeks before the start of the ragweed
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 score (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.
The first study compared RAGWITEK (n=187) relative to placebo (n=188) in
patients 18 through 50 years of age of whom approximately 22 percent had
mild asthma of a severity that required, at most, a daily low dose of an
inhaled corticosteroid, and 85 percent were sensitized to other
allergens in addition to short ragweed. Patients treated with RAGWITEK
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 peak ragweed pollen season, compared to placebo;
difference of RAGWITEK (n=159) relative to placebo (n=164) was -26
percent (95% CI: -38.7%; -14.6%).
The second study compared RAGWITEK (Short Ragweed Pollen Allergen
Extract) (n=194) to placebo (n=198) in patients 18 to 50 years of age,
of whom approximately 17 percent had mild asthma of a severity that
required, at most, a daily low dose of an inhaled corticosteroid, and 78
percent were sensitized to other allergens in addition to short ragweed.
The results of Study 2 were similar to Study 1. Patients treated with
RAGWITEK experienced significant reduction of nasal and ocular symptoms,
and significant reduction in use of symptom-relieving allergy
medication, as measured by decrease in the TCS for the peak ragweed
pollen season compared to placebo; difference of RAGWITEK (n=152)
relative to placebo (n=169) was -24 percent (95% CI: -36.5%; -11.3%).
About allergic rhinitis due to short ragweed pollen
It is estimated that approximately 4.5 million adults ages 20 to 64 in
the U.S. have been diagnosed with moderate to severe allergic rhinitis
and are sensitized to short ragweed pollen.
Important safety information about RAGWITEK
WARNING: SEVERE ALLERGIC REACTIONS
RAGWITEK can cause life-threatening allergic reactions such as
anaphylaxis and severe laryngopharyngeal restriction. Do not administer
RAGWITEK 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. RAGWITEK may not be suitable for patients
with certain underlying medical conditions that may reduce their ability
to survive a serious allergic reaction. RAGWITEK may not be suitable for
patients who may be unresponsive to epinephrine or inhaled
bronchodilators, such as those taking beta-blockers.
RAGWITEK 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 (gelatin, mannitol
and sodium hydroxide) contained in the product.
RAGWITEK can cause systemic allergic reactions including anaphylaxis
which may be life-threatening and 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 RAGWITEK (Short
Ragweed Pollen Allergen Extract). 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 RAGWITEK. Review the epinephrine package insert for
Administer the initial dose of RAGWITEK 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 RAGWITEK.
Patients who have persistent and escalating adverse reactions in the
mouth or throat should be considered for discontinuation of RAGWITEK.
Eosinophilic esophagitis has been reported in association with
sublingual tablet immunotherapy. Discontinue RAGWITEK and consider a
diagnosis of eosinophilic esophagitis in patients who experience severe
or persistent gastro-esophageal symptoms including dysphagia or chest
RAGWITEK has not been studied in patients with moderate or severe
asthma. Immunotherapy with RAGWITEK should be withheld if the patient is
experiencing an acute asthma exacerbation. Reevaluate patients who have
recurrent asthma exacerbations and consider discontinuation of RAGWITEK.
RAGWITEK 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 RAGWITEK 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 patients 18 years of age
and older treated with RAGWITEK vs. placebo included throat irritation
(16.6% vs. 3.3%), oral pruritus (10.9% vs. 2.0%), ear pruritus (10.4%
vs. 1.1%) and oral paraesthesia (10.0% vs. 4.0%).
Because systemic and local adverse reactions with immunotherapy may be
poorly tolerated during pregnancy, RAGWITEK 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); American
College of Allergy, Asthma & Immunology (ACAAI); or American
Academy of Otolaryngic Allergy (AAOA).
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# # #
Please see Prescribing Information, including Boxed Warning, for
RAGWITEK [Short Ragweed Pollen Allergen Extract] Tablet for Sublingual
Use at http://www.merck.com/product/usa/pi_circulars/r/ragwitek/ragwitek_pi.pdf
and Medication Guide for RAGWITEK at http://www.merck.com/product/usa/pi_circulars/r/ragwitek/ragwitek_mg.pdf.
RAGWITEK™ is a registered trademark of Merck
& Co., Inc., Whitehouse Station, N.J., USA.
Pamela Eisele, 267-305-3558
Robert Consalvo, 908-423-6595
Carol Ferguson, 908-423-4465
Justin Holko, 908-423-5088