Sublingual Oralair Recommended for Grass Pollen Allergy

Troy Brown, RN

December 11, 2013

The Allergenic Products advisory committee of the US Food and Drug Administration (FDA) voted unanimously to recommend Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass Mixed Pollens Allergen Extract Tablet for Sublingual Use (Oralair, Stallergenes, Inc) for the treatment of persons aged 10 to 65 years with grass pollen-induced allergic rhinitis or conjunctivitis confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for any of the five grass species included in this product, with the understanding that auto-injected epinephrine be made available at home.

The committee was originally asked to vote on recommending Oralair for those aged 5 years and older, but decided to limit their recommendation because the number of children aged 5-9 studied is small, and studies excluded patients older than 65 years.

Many patients with allergies find that pharmacologic treatments are ineffective or difficult to tolerate. Subcutaneous immunotherapy is currently available in the US but injections cause discomfort and are inconvenient because patients must receive injections in a healthcare provider’s office. Oralair is already approved in Europe and, if approved, it will be the first sublingual allergen immunotherapy in the US.

Oralair is dispensed in 100 index of reactivity (IR) and 300 IR tablets. The company uses index of reactivity as a potency measurement that defines 100 IR as the "concentration that elicits by skin prick test (SPT) a geometric mean wheal size of 7 mm diameter in 30 subjects who are sensitive to the corresponding allergen", according to a company briefing.

A 3-day escalation phase (100 IR on day 1, 200 IR on day 2, and 300 IR on day 3) is followed by the maintenance phase (300 IR once daily). Treatment is begun 4 months before, and throughout, the grass pollen season. The patient receives the first dose at the healthcare provider's office and takes the remaining doses at home.

Clinical Scores Reduced

The vote followed a discussion of data from 1 clinical study conducted in the US under an investigational new drug application (IND), and 5 studies conducted in Europe (not under IND). One of those studies was in pediatric patients.

Across all studies those who took 300 IR for 4 months before, and during, grass pollen season experienced a reduced clinical score as assessed by Average Adjusted Symptom Score (AASS), Average Rhinoconjunctivitis Total Symptom Score (ARTSS), or Average Combined Score (ACS), which is a combined symptom and rescue medication score. The 95% confidence interval upper limit for the change in primary endpoint score was between -13.0% and -19.6% for the grass pollen season during which patients received treatment.


In the adult pooled analysis, the most common treatment emergent adverse events (TEAEs) in patients who received the study drug were oral pruritus (32.6% Oralair; 6.6% placebo) and throat irritation (21.1% Oralair; 3.8% placebo).

In the 300 IR study groups, 13 (1.3%) Oralair recipients and 5 (0.6%) placebo recipients reported at least 1 serious TEAE. Two patients who received Oralair reported laryngopharyngeal disorders that were determined to be related to the drug. A 43-year-old female was hospitalized with gastroenteritis and treated with antibiotics 93 days after starting Oralair. This was determined to be possibly related to the drug. There were no reports of anaphylaxis, epinephrine administration, or deaths.

In the children/adolescents pooled analysis, the most frequently reported TEAEs were oral pruritus (33.1% Oralair; 4.3% placebo), mouth edema (12.9% Oralair; 0.0% placebo), and throat irritation (9.4% Oralair; 5.0% placebo).

One (0.6%) study drug recipient and 2 (1.3%) placebo recipients reported at least 1 serious TEAE, none of which were determined by the investigator to be related to the study drug.

The single serious TEAE in the study drug group was a mild asthma exacerbation. There were no reports of anaphylaxis, epinephrine use, severe laryngopharyngeal disorders, or deaths.

The company reported that in the post-marketing data from outside the US, more than 20 million doses have been given to 112,330 patients including 37,245 children and adolescents. The company has received 662 reports of adverse drug reaction (580 spontaneous reports and 82 reports from post-marketing studies). A total of 104 reports were serious; no deaths or long-term sequelae were reported. The most frequent reports were of mouth edema and throat irritation.

Asthma Concerns

Several committee members questioned whether some reports of oral pruritus, mouth edema, and throat irritation could have been anaphylactic reactions and expressed concern about giving Oralair to those with asthma. For this reason, the committee decided to require patients to have auto-injected epinephrine available.

"I don't think we can confidently say that there's not an issue with asthma because the formal studies specifically excluded anybody who was on a controller medication…we don't have studies formally performed on patients who have persistent asthma," said voting committee member John M. Kelso, MD, from the Division of Allergy, Asthma and Immunology, Scripps Clinic, San Diego, California.

"In addition to safety studies for patients with persistent asthma, I think efficacy studies for allergic asthma would be great," said voting committee member Michelle Lierl, MD, adjunct professor of pediatrics, Division of Allergy/Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. She added that in her practice subcutaneous immunotherapy improves symptoms in many of her patients with allergic asthma.

The advisory committee members have disclosed no relevant financial relationships.

FDA briefing, Stallergenes briefing


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