Background: Subcutaneous immunotherapy has emerged as an effective option for treating allergic diseases. Here, we assessed the clinical impact of the mannan‐conjugated birch pollen polymerized allergoid T502 in birch pollen‐induced allergic rhinoconjunctivitis. Methods: In this prospective, randomized, double‐blind placebo‐controlled phase III trial, 298 birch pollen–allergic adult patients were treated across 28 trial sites in Germany. Patients received either placebo or 23,000 mTU T502 subcutaneously over five pre‐seasonal visits. Efficacy was assessed by comparing the combined symptom and medication score (CSMS) between placebo and T502 during the peak birch pollen season 2022. Safety, tolerability and immunologic effects were also analyzed. Results: During the peak birch pollen season, the median CSMS of the T502 group was reduced by 33% ( p = 0.002) compared to placebo. The median daily symptom score and daily medication score were reduced by 30.4% ( p < 0.001) and 56.3% ( p = 0.045), respectively. Health related quality of life improved as reflected by reduction of RQLQ values by 31.5% ( p < 0.0001). Production of Bet v 1 sIgG4 and Bet v 1 sIgG increased up to 6.2‐fold and 3‐fold respectively in the T502 group ( p < 0.0001). The sIgE/sIgG4 ratio was strongly reduced in the T502 group at V7 (−62.9%, p < 0.0001). No fatalities nor serious adverse events were reported. In total, 16 systemic allergic reactions occurred (Grade I/II). Conclusions: Treatment with T502 significantly reduced symptoms and medication need in rhinoconjunctivitis patients. The treatment is well tolerated and safe.

Background/Objectives: Allergen immunotherapy (AIT) is the only disease-modifying treatment for grass pollen allergy. However, the proportion of patients interested in AIT who meet guideline-defined eligibility criteria remains unclear. This study aimed to characterise symptom burden, medication use, and AIT eligibility in adult patients with grass pollen allergy during the peak pollen season. Methods: In this multicentre, prospective, non-interventional epidemiological study, 479 adults with confirmed grass pollen allergy recorded daily nasal, ocular, and systemic symptoms, as well as anti-allergic medication use, via a validated electronic diary (CCC STUDY Diary) over a 30-day period in June/July 2025. A combined symptom–medication score (CSMS) was calculated daily, with a predefined threshold of ≥1.5 indicating clinically relevant symptom severity and potential eligibility for AIT. Both additive and weighted calculation approaches for the CSMS and the daily medication score (dMS) were evaluated to assess methodological robustness and reproducibility. Results: The mean additive CSMS was 2.14, indicating moderate symptom burden. Overall, 63.3% of participants exceeded the CSMS threshold of 1.5 and were considered eligible for AIT. Sensitivity analyses demonstrated excellent concordance between additive and weighted CSMS/dMS calculations (Spearman’s ρ >0.98; p < 0.001), and Bland–Altman analysis confirmed minimal bias (0.157) and narrow limits of agreement. Asthma was reported as a comorbidity in 36% of patients, generally associated with mild to moderate daily respiratory symptoms. Limitations included the self-reported nature of the data and a slightly reduced sample size; however, the results are representative of adult patients seeking care in specialised allergy centres in Germany. Conclusions: The CSMS also in its additive and therefore modernised form is a reliable, reproducible, and clinically meaningful tool for quantifying symptom severity and identifying patients suitable for AIT. Approximately two-thirds of adults interested in grass pollen AIT exhibited moderate to severe symptoms and were eligible for treatment according to current guideline recommendations.

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.

Background/Objectives: The guideline on allergen-specific immunotherapy of the European Academy of Allergy and Clinical Immunology recommends subcutaneous allergen-specific immunotherapy for the treatment of allergic rhinitis in children and adults with moderate to severe symptoms. The five years cohort study described below was designed in 2020 to demonstrate non-inferiority in terms of safety, tolerability and efficacy in a paediatric population compared with adult patients treated with microcrystalline tyrosine-adsorbed allergoids for their tree and grass pollen allergy in a perennial setting. Here, we present the preliminary findings from the first year. Methods: The Combined Symptom and Medication Score was chosen as the primary endpoint of this therapy. Secondary endpoints include the Rhinoconjunctivitis Quality of Life Questionnaire, the retrospective Rhinoconjunctivitis score, the Asthma Control Test and the Rhinitis Control Test, as well as an analysis of adverse drug reactions. Results: A total number of 320 patients were enrolled into this study, with 129 of these patients in the age group between 5 and 17 years and 191 patients in the adult age group. Mean Combined Symptom and Medication Score values did not differ significantly between minors and adults in the first pollen season after treatment induction. The retrospective score showed a strong and significant reduction in rhinoconjunctivitis and asthma symptoms. Treatment was well tolerated, with more than 80% of patients reporting no adverse drug reactions. Conclusions: The validity of this study approach of a cohort study has been confirmed by this first interim analysis for the initial course of therapy in the first year.

Background/Objectives: Allergen immunotherapy (AIT) is the only disease-modifying treatment for grass pollen allergy. However, the proportion of patients interested in AIT who meet guideline-defined eligibility criteria remains unclear. This study aimed to characterise symptom burden, medication use, and AIT eligibility in adult patients with grass pollen allergy during the peak pollen season. Methods: In this multicentre, prospective, non-interventional epidemiological study, 479 adults with confirmed grass pollen allergy recorded daily nasal, ocular, and systemic symptoms, as well as anti-allergic medication use, via a validated electronic diary (CCC STUDY Diary) over a 30-day period in June/July 2025. A combined symptom-medication score (CSMS) was calculated daily, with a predefined threshold of ≥1.5 indicating clinically relevant symptom severity and potential eligibility for AIT. Both additive and weighted calculation approaches for CSMS and the daily medication score (dMS) were evaluated to assess methodological robustness and reproducibility. Results: The mean additive CSMS was 2.14, indicating moderate symptom burden. Overall, 63.3% of participants exceeded the CSMS threshold of 1.5 and were considered eligible for AIT. Sensitivity analyses demonstrated excellent concordance between additive and weighted CSMS/dMS calculations (Spearman’s ρ >0.98; p<0.001), and Bland–Altman analysis confirmed minimal bias (0.157) and narrow limits of agreement. Asthma was reported as a comorbidity in 36% of patients, generally associated with mild to moderate daily respiratory symptoms. Limitations included the self-reported nature of the data and a slightly reduced sample size; however, the results are representative of adult patients seeking care in specialised allergy centres in Germany. Conclusions: The CSMS also in its additive and therefore modernized form is a reliable, reproducible, and clinically meaningful tool for quantifying symptom severity and identifying patients suitable for AIT. Approximately two-thirds of adults interested in grass pollen AIT exhibited moderate to severe symptoms and were eligible for treatment according to current guideline recommendations.

Background/Objectives: Previous studies have demonstrated the safety of pre-seasonal treatment with the mannan-conjugated birch pollen allergoid EP-088-T502. However, the safety of a combined pre- and co-seasonal treatment regimen has not yet been investigated. As climate change is associated with earlier and less predictable onset of birch pollen seasons, planned pre-seasonal allergen immunotherapy may unintentionally overlap with natural pollen exposure. Therefore, evaluation of the safety of treatment administered during the pollen season is of increasing clinical relevance. This study aimed to compare, in a purely descriptive manner, the safety and tolerability of pre-seasonal versus pre- and co-seasonal treatment with EP-088-T502. Methods: In this prospective, open-label, phase III trial (T502-SIT-059) (EudraCT No.: 2022-004082-20), patients (N = 109) who had participated in a preceding pivotal phase III study were offered continuation treatment with active EP-088-T502 (10,000 mTU/mL) across five treatment visits. For the subgroup analysis, all patients who completed their last treatment visit before 9 April 2023 (and, thus, before the start of the birch pollen season in Germany) were assigned to the pre-seasonal group (N = 20). Those who performed the last treatment visit thereafter were assigned to the pre-/co-seasonal group (N = 83). Due to post hoc subgroup allocation and unequal subgroup sizes, all subgroup analyses were purely descriptive. Results: No deaths nor serious adverse events (SAEs) were reported during the study. No epinephrine administration was required. Systemic adverse drug reactions (SADRs, N = 3) occurred in two patients who had previously received placebo. No grade III or IV systemic reactions, according to the German AWMF classification, were observed. Patients receiving pre- and co-seasonal treatment developed smaller wheals (mean diameter) compared with the pre-seasonal group (immediate reactions: 0.6 vs. 0.7 cm; late-phase reactions: 0.3 vs. 0.4 cm at the last treatment visit). This was also reflected in the medians (immediate reactions: 0.2 cm vs. 0.4 cm; late-phase reactions: 0.2 vs. 0 cm at the last treatment visit). Of all AEs that were (possibly) related to EP-088-T502 (N = 89), 74 (83%) occurred at the first three treatment visits (before the birch pollen season). The frequency of AEs appeared descriptively similar between groups for the last two treatment visits. Patients who had received placebo in the previous trial experienced more treatment-related side effects compared to patients who had already received EP-088-T502 in the previous year. Conclusions: These data suggest that EP-088-T502 is safe and well-tolerated, even when administered during the birch pollen season, regardless of prior exposure to EP-088-T502.