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 polallergoid 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 analysed. Results: During the peak birch pollen season, the median CSMS of the T502 group was reduced by 33.00% (p=0.002) compared to placebo. The median daily symptom score and daily medication score were reduced by 30.43% (p<0.001) and 56.25% (p=0.045), respectively. Health related quality of life improved as reflected by reduction of RQLQ values by 31.54% (p<0.0001). Production of Bet v 1 sIgG4 and 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 (-62.90%, 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.

Response to Correspondence ALL-2023-01107 “Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy”P.J. de Kam1, S. Zielen2, J.A. Bernstein3, U. Berger4, M. Berger5, M. Cuevas6, D. Cypcar7, A. Fuhr-Horst8, W.A. Greisner9, M. Jandl10, S. Laßmann11, M. Worm12, J. Matz13, E. Sher14, C. Smith15, G.C. Steven16, R. Mösges17,18, M.H. Shamji19,20, L. DuBuske21, F. Borghese1, K. Oluwayi1, T. Zwingers1, M. Seybold1, O. Armfield1, M.D. Heath1, S.J. Hewings1, M.F. Kramer1, M.A. Skinner1Allergy Therapeutics plc, Worthing, United KingdomChildren and Adolescents Dept., Allergology, Pulmonology & Cystic fibrosis, Goethe University, Frankfurt, GermanyBernstein Clinical Research Center, LLC, Cincinnati, OH, United States of AmericaAerobiology and Pollen Research Unit, Dept. Oto-Rhino-Laryngology, Medical University Vienna, Vienna, Austria.Wiener Gesundheitsverbund, Hospital Hietzing, Department of Otorhinolaryngology, Vienna, AustriaClinic and Polyclinic of Otorhinolaryngology, University Clinic Carl Gustav Carus, TU Dresden, GermanyAllergy Partners of Western North Carolina, Asheville, NC, United States of AmericaENT Research- Institut für klinische Studien, Essen, GermanyBluegrass Allergy Research, Lexington, KY, United States of AmericaHamburger Institut für Therapieforschung GmbH, Hamburg, GermanyStudienzentrum Dr. Sabine Laßmann, Saalfeld, GermanyUniversitätsmedizin Berlin, Department of Dermatology and Allergy - Charite Campus Mitte, Berlin, GermanyChesapeake Clinical Research, Inc. White Marsh, MD, United States of AmericaAllergy Partners of New Jersey, Ocean, NJ, United States of AmericaCertified Research Associates, Cortland, NY, United States of AmericaAllergy Asthma & Sinus Center, S.C., Greenfield, WI, United States of AmericaIMSB (Institute of Computational Biology and Medical Statistics), University at Cologne, Cologne, GermanyClinCompetence, Cologne, GermanyImmunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College London, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, United KingdomDivision of Allergy and Immunology, Department of Internal Medicine, George Washington University Hospital, Washington, DC, United States of America

CORRIGENDUMDate: 09 Feb 2024Manuscript number: ALL-2023-01229.R1Title of Article: Response to Correspondence ALL-2023-01107 “Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy”Authors: P.J. de Kam1, S. Zielen2, J.A. Bernstein3, U. Berger4, M. Berger5, M. Cuevas6, D. Cypcar7, A. Fuhr-Horst8, W.A. Greisner9, M. Jandl10, S. Laßmann11, M. Worm12, J. Matz13, E. Sher14, C. Smith15, G.C. Steven16, R. Mösges17,18, M.H. Shamji19,20, L. DuBuske21, F. Borghese1, K. Oluwayi1, T. Zwingers1, M. Seybold1, O. Armfield1, M.D. Heath1, S.J. Hewings1, M.F. Kramer1, M.A. Skinner1Allergy Therapeutics plc, Worthing, United KingdomChildren and Adolescents Dept., Allergology, Pulmonology & Cystic fibrosis, Goethe University, Frankfurt, GermanyBernstein Clinical Research Center, LLC, Cincinnati, OH, United States of AmericaUniversity of Innsbruck, Department of Botany, Innsbruck, AustriaWiener Gesundheitsverbund, Hospital Hietzing, Department of Otorhinolaryngology, Vienna, AustriaClinic and Polyclinic of Otorhinolaryngology, University Clinic Carl Gustav Carus, TU Dresden, GermanyAllergy Partners of Western North Carolina, Asheville, NC, United States of AmericaENT Research- Institut für klinische Studien, Essen, GermanyBluegrass Allergy Research, Lexington, KY, United States of AmericaHamburger Institut für Therapieforschung GmbH, Hamburg, GermanyStudienzentrum Dr. Sabine Laßmann, Saalfeld, GermanyUniversitätsmedizin Berlin, Department of Dermatology and Allergy - Charite Campus Mitte, Berlin, GermanyChesapeake Clinical Research, Inc. White Marsh, MD, United States of AmericaAllergy Partners of New Jersey, Ocean, NJ, United States of AmericaCertified Research Associates, Cortland, NY, United States of AmericaAllergy Asthma & Sinus Center, S.C., Greenfield, WI, United States of AmericaIMSB (Institute of Computational Biology and Medical Statistics), University at Cologne, Cologne, GermanyClinCompetence, Cologne, GermanyImmunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College London, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, United KingdomDivision of Allergy and Immunology, Department of Internal Medicine, George Washington University Hospital, Washington, DC, United States of AmericaName of the Corresponding Author: Pieter-Jan De Kam