Regulatory Decision Summary for Itulatek

For tree pollen allergic patients, symptoms typically comprise allergic rhinitis and/or conjunctivitis (AR/C) and to a lesser extent asthma. Although usually not regarded as a serious disease, AR/C may affect quality of life, social life, school learning performance and work productivity. Furthermore, AR/C is regarded as one of the major risk factors for the development of asthma. 10-40% of people with AR/C suffer from asthma.

Treatment of allergic rhinitis induced by tree pollens in Canada currently consists of allergen avoidance and symptom-relieving medication with agents such as antihistamines and glucocorticoids. These therapies do not treat the underling disorder of the disease. A large proportion of patients on symptom-relieving medication have poor or only partial symptom control. AIT, such as Itulatek, has a potential to modify the natural course of allergic disease by induction of tolerance.

Authorization for Itulatek was based on 4 randomised, double-blind, placebo-controlled clinical trials conducted in Europe and Canada, including a Phase I trial, a Phase II dose-finding field trial, a Phase II dose-finding EEC trial and one pivotal Phase III field trial. The population of theses trials was mostly adult patients who had a history of birch pollen-induced moderate-to-severe rhinoconjunctivitis, with or without asthma, despite having received treatment with symptom relieving medication during the previous two tree pollen seasons.

A total of 1084 subjects (12-65 years) were exposed to any dose of the SQ tree SLIT-tablet during the clinical development program. Of the total population exposed to 12 SQ-Bet, 35 subjects (7%) were adolescents (12-17 years).

The clinical studies demonstrated the efficacy of Itulatek in the birch pollen season (BPS) and alder/hazel pollen season (AHPS). Primary efficacy analysis in the Phase III pivotal trial showed that patients treated with Itulatek (12 SQ-Bet) had a significant reduction (35.69%) in total combined score (TCS) during BPS compared to placebo-treated patients (p<0.0001). Statistically significant reductions were also observed for all key secondary endpoints including daily symptom score (DSS) during the BPS. Treatment with Itulatek (12 SQ-Bet) also resulted in significant reductions in average daily medication score (DMS) by 44.42% in BPS (p<.0001) compared to placebo treatment.

The majority (82.0%) of subjected treated with12 SQ-Bet reported at least 1 AE.

The most frequently reported AEs were local allergic reactions, such as oral pruritus, throat irritation, tongue pruritus, oral paraesthesia and pharyngeal oedema. Majority of most frequently reported IMP-related AEs were mild or moderate in intensity with about 4% subjects experiencing severe AEs. Severe IMP-related AEs reported by ≥ 1% of subjects treated with 12 SQ-Bet were throat irritation (2%) and oral pruritus (1%). The majority of AEs had median onset within the first week of treatment.

During the clinical development program, one subject treated with 8 SQ-Bet experienced an anaphylactic reaction. Severe reactions that affected the throat included throat tightness (n = 1), pharyngeal edema (n = 1) and dysphagia (n = 1). One subject treated with 1 SQ-Bet experienced severe treatment-related asthma. Epinephrine was administered to 3 subjects on active treatment for events of anaphylactic reaction, asthma and angioedema.

Overall, the safety analysis showed that Itulatek at the dose of 12 SQ-Bet was well tolerated and suitable for self-administration in adults, when the first dose is administered under medical supervision for at least 30 minutes, and shown to be tolerable. The observed safety profile of Itulatek was consistent with those of SLIT-tablet products approved in Canada.

In conclusion, the ratio of benefit/risk for Itulatek (12 SQ-Bet) is considered favorable in treatment of moderate to severe seasonal allergic rhinitis, with or without conjunctivitis, induced by tree pollen from birch, alder or/and hazel in adults.