Grastek Recommended by FDA Panel for Timothy Grass Allergy

Troy Brown

December 12, 2013

The Allergenic Products Committee of the US Food and Drug Administration (FDA) voted unanimously to recommend Timothy Grass Pollen Allergen Extract Tablet for Sublingual Use (MK-7243) (Grastek, Merck Sharp & Dohme Corp) for the treatment of Timothy grass pollen–induced allergic rhinitis, with or without conjunctivitis, in individuals aged 5 to 65 years, with the understanding that autoinjected epinephrine will be available to patients at home.

In North America, grass pollen is one of the most common allergens to provoke allergic symptoms, and Timothy is the most prevalent grass, pollinating heavily throughout the continent. Current treatment consists of allergen avoidance and pharmacotherapies, including antihistamines, leukotriene antagonists, and intranasal corticosteroids.

The most common form of immunotherapy in North America, subcutaneous allergen immunotherapy is the only treatment known to have long-term benefit and change the course of respiratory allergic disease. Sublingual immunotherapy is currently not available in the United States.

MK-7243 has been on the market in Europe since 2006 under the trade name Grazax. Each tablet contains 2800 bioequivalent allergy units of the drug substance. The recommended dose is 1 sublingual tablet daily; patients begin treatment 12 weeks before and continue throughout the grass pollen season. The first dose is given at the healthcare provider's office; all other doses are taken at home. The tablet dissolves in less than 10 seconds, according to the company briefing.

The rapid dissolvability is an advantage of this medication, particularly with young children, who may have difficulty holding a tablet under their tongue for several minutes, said voting committee member Vivian Saper, MD, adjunct associate professor, Department of Pediatrics, Program in Immunology at Stanford University Medical Center, California. "That concern was allayed by having a tablet that instantly dissolves," Dr. Saper explained.

The vote follows a discussion of data from five phase 1 studies, two phase 2 studies, six phase 3 studies, and 2 studies identified as phase 4 European studies.

Efficacy

All studies included patients with concomitant asthma, but none included patients with severe or unstable asthma. Autoinjected epinephrine was provided to all patients enrolled in the US studies.

The primary efficacy endpoint in the phase 3 efficacy studies was the average rhinoconjunctivitis daily symptom score, the average rhinoconjunctivitis daily medication score, or the average combined rhinoconjunctivitis daily symptom score and daily medication score (total combined score) during the entire grass pollen season.

MK-7243 met the primary endpoints in the first grass pollen season in 3 (GT-08, P05238, P08067) of the 4 confirmatory efficacy trials, but not in the first North American trial (GT-14).

Safety

In pooled analyses of adult data, most adverse events occurred within the first 1 to 2 weeks of treatment, and the highest percentage of adverse events occurred on day 1. The treatment-emergent adverse events that were reported most frequently were oral pruritus (26.7%, MK-7243; 3.5%, placebo), throat irritation (22.6%, MK-7243; 2.8%, placebo), ear pruritus (12.5%, MK-7243; 1.1%, placebo), and mouth edema (11.1%, MK-7243; 0.8%, placebo).

A total of 25 (1.5%) MK-7243 and 22 (1.3%) placebo recipients reported at least 1 serious adverse event, none of which were considered treatment-related.

In pooled analyses of data from children and adolescents, most adverse events occurred within the first 1 to 2 weeks of treatment, and the highest percentage of adverse events occurred on day 1. The treatment-emergent adverse events that were reported most frequently were oral pruritus (24.4%, MK-7243; 2.1%, placebo), throat irritation (21.3%, MK-7243; 2.5%, placebo), mouth edema (9.8%, MK-7243; 0.2%, placebo), and tongue pruritus (9.2%, MK-7243; 0.9%, placebo).

A total of 5 (1.1%) MK-7243 and 7 (1.6%) placebo recipients reported at least 1 serious adverse event, including viral myocarditis (1 patient), synovitis (1 patient), and asthma (3 patients). One asthma episode occurred before randomization. None of the serious adverse events were considered treatment-related.

Additional Studies Needed

The committee members would like to see additional studies, particularly in patients with asthma and those in various racial groups, as well as long-term studies of efficacy and safety. None of the studies discussed today included patients older than 65 years.

"We do need some studies on different racial groups," said voting committee member Jane Peterson, RN, PhD, professor emeritus of nursing and anthropology, Seattle University College of Nursing in Washington.

"In addition to studies for persistent asthma for safety, I would like to suggest studies of efficacy for seasonal asthma," said voting committee member Michelle Lierl, MD, adjunct professor of pediatrics, Division of Allergy/Immunology, Cincinnati Children's Hospital Medical Center in Ohio.

The advisory committee members have disclosed no relevant financial relationships.

FDA Allergenic Products Committee Meeting. December 12, 2013.

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