Ragwitek by Merck & Co, Inc, and Catalent Pharma

Pharmacy Times, October 2014 Diabetes, Volume 80, Issue 10

The FDA has approved sublingual Ragwitek (Short Ragweed Pollen Allergen Extract) tablets as an immunotherapy option for selected patients with confirmed ragweed pollen—induced allergic rhinitis.

On April 17, 2014, the FDA announced approval of Ragwitek, a sublingual immunotherapy treatment for patients with pollen-induced allergic rhinitis, with or without conjunctivitis. Qualifying patients include adults 18 through 65 years of age who have a positive test result for ragweed (Ambrosia artemisiifolia) allergy through skin testing or through IgE antibody testing.1,2

Ragwitek carries a Black Box warning for life-threatening allergic reactions, including anaphylaxis and severe laryngopharyngeal restriction. Importantly, this Black Box warning precludes use of Ragwitek in patients with severe, unstable or uncontrolled asthma and other medical conditions that may diminish the ability to survive an anaphylactic reaction. Other contraindications for use include a history of eosinophilic esophagitis or a severe systemic allergic reaction to sublingual allergen immunotherapy.2

Mechanism of Action

As with any allergen immunotherapy, the precise mechanism of action of Ragwitek is unknown. Pharmacologists report that the treatment may mediate immune cell development, including T and B regulatory cells, and IgG4 antibodies that recognize allergens.2,3

How Supplied

Sublingual Ragwitek tablets are white to off-white tablets supplied in blister-pack sheets containing 10 tablets each, which are packed in 30- and 90-tablet boxes. To protect the medication from moisture, tablets should be stored in the original blister pack until they are used.2

Dosage and Administration

Each tablet of Ragwitek contains 1 Antigen E unit of short ragweed pollen allergen extract. When administered, tablets should be removed from the foil packaging with dry hands and immediately placed under the tongue. Patients should be advised not to eat or drink anything for at least 5 minutes after the tablet has dissolved.2,4

Patients receiving their first dose of Ragwitek should be observed in a physician’s office for at least 30 minutes, and should be monitored for signs of local or systemic allergic reaction. Subsequent daily doses may be administered at home, starting a minimum of 12 weeks before the start of ragweed season and continuing throughout the season.2

All patients receiving Ragwitek should have access to an epinephrine autoinjector, and all patients and/or caregivers should be familiarized with its proper use.2

Clinical Trials

Using a patient self-reported questionnaire of 4 types of nasal and 2 types of ocular symptoms, scientists evaluated the safety and efficacy of Ragwitek in a series of two 52-week trials, each of which started 12 weeks before ragweed season and included patients aged 18 to 50 years. On each of the 6 symptom dimensions, symptoms were rated from 0 (no symptoms) to 3 (severe symptoms) to arrive at a total combined score, or TCS.2,5,6

In the first trial, patients with allergic rhinitis induced by ragweed pollen were assigned to receive Ragwitek (n = 187) or placebo (n = 188) daily. Of these patients, 85% had sensitivities to allergens other than short ragweed. Peak TCSs were reduced by an average of 2.24 points, constituting a 26% reduction in the severity of symptoms.2,5

Unlike the first trial, the second trial excluded patients with allergies to types of pollen other than short ragweed pollen allergens. Patients with allergic rhinitis induced by ragweed pollen were assigned to receive Ragwitek (n = 194) or placebo (n = 198) daily. Peak TCSs were reduced by an average of 2.04 points, constituting a 24% reduction in the severity of symptoms.2,6

Warnings and Precautions

As no animal reproduction studies on Ragwitek have been performed to date, it is a Pregnancy Category C medication.2

Ragwitek may cause serious adverse events, including asthma exacerbation, anaphylactic reactions, oral inflammation, and impaired healing of oral wounds after oral surgery. Of 1057 patients treated in clinical trials, a single patient experienced a severe systemic allergic reaction but recovered fully.2

Common adverse events with Ragwitek included throat irritation, oral pruritus, ear pruritus, oral paraesthesia, mouth edema, and tongue pruritus.2

Michael R. Page earned his PharmD from the Ernest Mario School of Pharmacy at Rutgers University. He has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times

References

1. FDA approves Ragwitek for short ragweed pollen allergies. www.fda.gov/newsevents/newsroom/pressannouncements/ucm393820.htm. Published April 17, 2014. Accessed September 5, 2014.

2. RAGWITEK (Short Ragweed Pollen Allergen Extract) Tablet [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2014.

3. Cavkaytar O, Akdis CA, Akdis M. Modulation of immune responses by immunotherapy in allergic diseases. Curr Opin Pharmacol. 2014.

4. The Unified Code for Units of Measure. Amb a 1 Units - an arbitrary unit for the major allergen in short ragweed. http://unitsofmeasure.org/trac/ticket/30. Accessed September 5, 2014.

5. Nolte H, Hébert J, Berman G, et al. Randomized controlled trial of ragweed allergy immunotherapy tablet efficacy and safety in North American adults. Ann Allergy Asthma Immunol. 2013;110(6):450-456.

6. Creticos PS, Maloney J, Bernstein DI, et al. Randomized controlled trial of a ragweed allergy immunotherapy tablet in North American and European adults. J Allergy Clin Immunol. 2013;131(5):1342-1349.