Sustained Clinical Improvement in Birch Pollen Allergy After Two Pre‐Seasonal Short Courses of Allergen‐Specific Immunotherapy: A Long‐Term Open‐Label Extension Study

BACKGROUND: Mannan-conjugated allergoids represent an effective option for treating allergic diseases. This study evaluated the clinical impact of the mannan-conjugated, polymerised birch pollen allergoid EP-088_T502 in patients with birch pollen-induced allergic rhinoconjunctivitis over 3 years. METHODS: Following up to a double-blind, placebo-controlled dose-finding study, in this open, long-term extension study, 154 birch pollen-allergic patients were enrolled in Germany. Patients were treated with a cumulative dose of 48,000 mTU EP-088_T502 administered subcutaneously over five pre-seasonal visits in each of the two treatment years (2021, 2022) with a subsequent follow-up year in 2023. The primary efficacy endpoint was the combined symptom and medication score (CSMS) during the peak birch pollen season, which was compared with the CSMS of the placebo group during the peak pollen season of 2020. Safety, tolerability, and immunogenicity were also analysed. RESULTS: Compared to the placebo group of the preceding study, median CSMS during the peak birch pollen seasons showed reductions of 47.5% in 2021 (p < 0.001), 51.8% in 2022 (p < 0.001), and 36.5% in 2023 (p < 0.001). Median daily symptom scores were reduced by 40.7% in 2021 (p < 0.001), 40.7% in 2022 (p < 0.001), and 25.6% in 2023 (p < 0.010). Median daily medication scores reached 0.07 in 2021 and 0.04 in 2022 (p < 0.001) and were reduced by 65.9% in 2023 (p < 0.003). Immunological responses showed a 4.82-fold increase in Bet v1 sIgG4 (p = 0.001) and a marked decrease (-65.5%, p = 0.001) in the sIgE/sIgG4 ratio after the first treatment phase. EP-088_T502 demonstrated good safety and tolerability, with only six mild to moderate systemic allergic reactions (Grade I/II). No epinephrine was used. CONCLUSION: In this open-label study, two consecutive years of pre-seasonal short-course allergen immunotherapy (AIT) with EP-088_T502 markedly reduced symptoms and medication need in patients with birch pollen-induced rhinoconjunctivitis. Persistent therapeutic effects observed during the follow-up year, although limited by attrition of the study population, suggest sustained clinical improvement and indicate the potential disease-modifying impact of this treatment regimen.