ORALAIR Tablets Ref.[27771] Active ingredients: Grass pollen

No carcinogenicity studies were conducted in animals. There was no evidence of mutagenic or clastogenic activity in response to ORALAIR in the in vitro bacterial mutagenesis assay and mouse lymphoma thymidine kinase cell assay or the in vivo bone marrow micronucleus and unscheduled DNA synthesis tests in rats.

No fertility study was conducted with ORALAIR.

The efficacy of ORALAIR for the treatment of grass pollen-induced allergic rhinoconjunctivitis was investigated in five double-blind, placebo-controlled clinical trials: four natural field studies and an environmental exposure chamber study.

The natural field studies included these trials, each conducted over a single season (two in adults and one in adolescents and children) and one five-year study (adults). Participants received ORALAIR or placebo daily for four months prior to grass pollen season and throughout grass pollen season.

Study participants reported at least a two grass pollen season history of rhinoconjunctivitis symptoms. For the European studies, subjects had a positive skin prick test to 5-grass pollen extract and positive in vitro testing for timothy grass-specific serum IgE. For the US study, subjects had a positive skin prick test to Timothy grass pollen extract.

With the exception of those with mild intermittent asthma, patients with asthma were excluded. Approximately 16% had asthma at baseline and 65% were polysensitized (i.e., sensitized to the 5-grass pollen allergen extract and at least one other unrelated allergen). Overall, the mean age of study participants was 28 years and 56% were male.

Natural Field Studies

In the natural field studies, efficacy of ORALAIR as immunotherapy to treat symptoms of allergic rhinoconjunctivitis due to the grass pollens included in ORALAIR was assessed via daily recording of symptoms and rescue medication use. The daily Combined Score (CS, range: 0-3) equally weights symptoms and rescue medication use. The daily Rhinoconjunctivitis Total Symptom Score (RTSS, range 0-18) is the total of the six individual symptom scores (sneezing, rhinorrhea, nasal pruritus, nasal congestion, ocular pruritus and watery eyes) each graded by participants on a 0 (no symptoms) to 3 (severe symptoms) scale. The daily Rescue Medication Score (RMS, range 0-3) grades the intake of rescue medication as 0 = absent, 1 = antihistamine, 2 = nasal corticosteroid, 3 = oral corticosteroid. In case of multiple medications, the higher score is retained. Least Squares (LS) means are within-group means adjusted for the covariates in the statistical models (i.e., analyses of covariance for average scores and linear mixed models with repeated measures for daily scores). The Relative Difference is the LS mean difference between ORALAIR and Placebo divided by the LS mean of Placebo, expressed as a percentage.

US Study

In this study, 473 adults aged 18 through 65 years received ORALAIR or placebo, starting approximately four months prior to the expected onset of the grass-pollen season and continuing for the duration of the pollen season. The results of the analysis of the daily Combined Score (CS), daily Rhinoconjunctivitis Total Symptom Score (RTSS), and daily Rescue Medication Score (RMS) are summarized in Table 4.

Table 4. Daily Combined Score (CS), Daily Rhinoconjunctivitis Total Symptom Score (RTSS), and Daily Rescue Medication Score (RMS) during the Grass Pollen Period (US study):

^* LS: Least Squares
^† Primary efficacy analysis
^‡ Secondary efficacy analysis

European Study

In this study, adults aged 18 to 45 years received one of 3 different doses of 5-grass pollen extract sublingual tablet or placebo. A total of 311 subjects received ORALAIR or placebo starting approximately 4 months prior to the expected onset of the grass pollen season and continuing for the duration of the grass pollen season. The results of the analysis of the daily CS, daily RTSS and daily RMS for ORALAIR (300 IR) are shown in Table 5.

Table 5. Daily Combined Score (CS), Daily Rhinoconjunctivitis Total Symptom Score (RTSS), and Daily Rescue Medication Score (RMS) during the Grass Pollen Period (European study):

^* LS: Least Squares

Long Term Study

In this study, adults received ORALAIR or placebo according to two different treatment regimens. A total of 426 subjects received ORALAIR or placebo starting approximately 4 months prior to the grass pollen season and continuing for the entire season. Subjects were treated for three consecutive grass pollen seasons (Year 1 to Year 3). The primary evaluation was the Year 3 pollen period. Participants then entered two years of immunotherapy-free follow-up (Year 4 and Year 5). The results of the analysis of the daily Combined Score for ORALAIR (4M) for treatment Years 1-3 are summarized in Table 6. Data are insufficient to demonstrate efficacy for one or two years after discontinuation of ORALAIR.

Table 6. Analysis of Daily Combined Score for Each Grass Pollen Period (Long Term study):

^* LS: Least Squares

Pediatric Study

In this study, 278 children and adolescents 5 through 17 years of age received ORALAIR or placebo starting approximately 4 months prior to the grass-pollen season and continuing for the duration of the pollen season. The results of the daily CS, daily RTSS, and daily RMS are summarized in Table 7.

Table 7. Daily Combined Score (CS), Daily Rhinoconjunctivitis Total Symptom Score (RTSS), Daily Rescue Medication Score (RMS) during the Grass Pollen Period (Pediatric study):

^* LS: Least Squares

Allergen Environmental Chamber Study

In an allergen environmental chamber study, 89 adults with grass pollen-associated allergic rhinoconjunctivitis were challenged with four of the five grass pollens contained in ORALAIR at baseline and after 4 months of treatment with ORALAIR (n=45) or placebo (n=44). The average Rhinoconjunctivitis Total Symptom Score (RTSS) of each group during the 4 hours of the allergen challenge was assessed; use of rescue medication was not permitted. The results of this study are shown in Table 8.

Table 8. Average Rhinoconjunctivitis Total Symptom Score (RTSS) during Grass Pollen Allergen Challenge in an Environmental Exposure Chamber after 4 months of ORALAIR or placebo:

^* LS: Least Squares
^† Primary efficacy analysis