Meta‐Analysis of <scp>PQ</scp> Grass 27600 <scp>SU</scp> Efficacy and Quality of Life From Phase <scp>III</scp> Trials
Authors: Stefan Zielen, Jonathan A. Bernstein, Oliver Pfaar, Lawrence DuBuske, Ralph Mösges, Sven Becker, Fiona Sellwood, Matthias F. Kramer, Murray Skinner, Pieter‐Jan de Kam
Journal: Allergy (2025)

PQ Grass 27600 SU (PQ Grass) is a modified broad spectrum grass allergen subcutaneous immunotherapy (SCIT) product using MicroCrystalline Tyrosine and Monophosphoryl Lipid-A as an adjuvant system (Supporting Information; Table S1). Two highly comparable randomized double-blind, placebo-controlled field studies with PQ Grass (G309—EudraCT2020-000408-13 [1]; G306—EudraCT2019-001517-16 [2]) have been completed in the US and Europe (Supporting Information 2) and the positive results support a marketing authorisation application. Here, we report the EAACI recommended combined symptom medication score (CSMS0-6) [3] as the primary endpoint and the key secondary endpoint standardized rhinoconjunctivitis quality of life questionnaire score (RQLQ[S]) using a meta-analysis approach for PQ Grass. These results were compared to integrated analyses of adult Phase III studies of two registered sublingual immunotherapy (SLIT) products (Table S1) using Biologics License Applications (BLA) [4, 5] and recently published data [6]. This meta-analysis complied with the European Medicine Agency (EMA) guidance recommendations [7]. G309 [1] was an exploratory Phase II/III field study and G306 the pivotal Phase III study [2], the only two field studies performed with PQ Grass 27600 SU. The selection criteria were essentially equal; both studies used the same primary endpoint (CSMS0-6) averaged over the peak grass pollen season (GPS). For the PQ Grass meta-analysis, the individual data of the single study analyses were combined, and a common effects data integration was performed, using weights determined by study size [8, 9]. For the SLIT studies, the total treatment effect size and 95% CIs were derived from the summary statistics provided in the respective BLA reviews, using an integrated analysis strategy, weighing results based on study size. Although different CSMS endpoint definitions were applied for the SLIT products and PQ Grass, it was assumed that the calculated % change compared to placebo would enable comparison of different studies. In total 674 adult subjects with allergic rhinitis and/or rhinoconjunctivitis were included in this PQ Grass meta-analysis. It was confirmed that the primary outcomes between both studies were sufficiently homogeneous (x2 = 1.55, p = 0.21). The results of this meta-analysis showed a clinically relevant and statistically significant improvement of −22.5% (95% CI: −31.8% to −13.2%, p < 0.00004) compared to placebo on the primary endpoint CSMS0-6 (peak GPS) (Figure 1A). For the single-grass-extract-SLIT product only studies enrolling adults from the BLA [5] were included in the calculations, resulting in a relative treatment effect of −23.7% for the primary endpoint (Figure 1B). However, when considering all studies supporting the BLA [5] of this SLIT tablet (i.e., including pediatric studies), a treatment effect of −19.8% was reported [5]. The improvement calculated for the 5-grass-mix was −22.9% for adult trials (Figure 1C) [4]. In addition, PQ Grass [1, 2] showed a clinically relevant improvement on the RQLQ[S] of −0.51 points (95% CI: −0.72 to −0.29), corresponding to a relative improvement of −28.9% (95% CI: −40.4% to −17.3%; p < 0.00001), whereas an average RQLQ improvement of −0.20 and −0.34 points was calculated for the single-grass-extract-SLIT and 5-grass-mix, respectively [4, 6] (Figure 2). While the designs of the two PQ Grass studies included in this meta-analysis were highly similar, it should be noted that there are known limitations regarding I-squared value and Chi-Square Statistic in a setting with only a few studies, and these statistics should be interpreted cautiously. Furthermore, a long-term pediatric Phase III study was recently started with PQ Grass (EUCT number 2023-508520-36-00) and the 1-year data will soon expand this meta-analysis. In conclusion, PQ Grass 27600 SU is an innovative short-course allergen-specific grass SCIT product applying a potent adjuvant system, showing a clinically meaningful strong primary efficacy response and quality of life improvement for two highly comparable field studies. The meta-analysis demonstrated that the primary endpoint effect size after PQ Grass was highly comparable with that of two registered grass SLIT products. PQ Grass showed a tendency towards more pronounced improvements in rhinitis quality of life compared to grass SLIT. Stefan Zielen, Fiona Sellwood, Matthias F. Kramer, Murray Skinner, Pieter-Jan de Kam: idea and conceptualisation of meta-analysis and integrated data analysis. Pieter-Jan de Kam: data analysis. Stefan Zielen, Jonathan A. Bernstein, Oliver Pfaar, Lawrence DuBuske, Ralph Mösges, Sven Becker, Fiona Sellwood, Matthias F. Kramer, Murray Skinner, Pieter-Jan de Kam: contextualisation of results. Matthias F. Kramer, Murray Skinner, Pieter-Jan de Kam: manuscript drafting. Stefan Zielen, Jonathan A. Bernstein, Oliver Pfaar, Lawrence DuBuske, Ralph Mösges, Sven Becker, Fiona Sellwood, Matthias F. Kramer, Murray Skinner, Pieter-Jan de Kam: manuscript editing. All authors critically revised the manuscript and approved the submission of the final version. The authors acknowledge the active contribution of the investigators and project teams of both herein analyzed PQ Grass 27600 SU studies and all participating patients. The authors are grateful to A. Graessel and S. Starchenka for their support in writing, editing, formatting, and publishing this manuscript. S.Z. has received personal fees for lectures from Engelhard GmbH, from Böhringer Ingelheim, Allergy Therapeutics, AstraZeneca, SanofiAventis, EryDel SpA, and Lofarma during the last 3 years. J.A.B. is acting as a consultant and PI forAllergy Therapeutics, Stallergens, ALK, Eli Lilly, Novartis, Genentech, Sanofi Regeneron, A.Z., G.S.K., and Amgen. O.P. reports grants for his institution as a clinical trial unit for RESONATE from Allergy Therapeutics PLC, UK; and he reports grants and/or personal fees and/or travel support from AEDA, Alfried Krupp Krankenhaus, ALK-Abelló, Allergopharma, Almirall, Altamira Therapeutics, ASIT Biotech, AstraZeneca, Bencard Allergie GmbH/Allergy Therapeutics, Blueprint, Cliantha, Deutsche AllergieLiga e.V., Deutsche Forschungsgemeinschaft, Dustri-Verlag, ECM Expro&Conference Management GmBH, Forum für Medizinische Fortbildung, Georg-Thieme-Verlag, GSK, HAL Allergy Holding B.V./HAL Allergie GmbH, Immunotek, Ingress Health, Institut für Disease Management (Essen, Germany), IQVIA Commercial, Japanese Society of Allergology, Königlich Dänisches Generalkonsulat, Laboratorios LETI/LETI Pharma, Lilly, Lofarma, Medizinische Hochschule Hannover, med update europe GmbH, Meinhardt Congress GmbH, Novartis, Paul-Ehrlich-Institut, Paul-Martini-Stiftung, PneumoLive, Pohl-Boskamp, Procter & Gamble, Red Maple Trials Inc., R.G. Aerztefortbildung, ROXALL Medizin, Sanofi Aventis, Sanofi Genzyme, Springer Publisher, Stallergenes Greer, streamedup! GmbH, Technical University Dresden, Wiley Publishers, Wort & Bild Verlag, Verlag ME, all outside the submitted work. O.P. is Vice President of the European Academy of Allergy and Clinical Immunology (EAACI), a member of EAACI Excom, as well as a member of the external board of directors of the German Society of Allergy and Clinical Immunology (DGAKI); coordinator, main- or co-author of different position papers and guidelines in rhinology, allergology, and allergen-immunotherapy; and he is Editor-in-Chief of Clinical Translational Allergy and Associate Editor of Allergy. LDB acts as a consultant for Allergy Therapeutics and a Consultant and/or Speakers Bureau for GSK, Sanofi, Regeneron, Astra Zeneca, ALK-Abello, Amgen, Bryn Pharm, and Areteia. JALreports grants via Biomedical Research Funding (Imperial College BRC), all outside the submitted work. R.M. reports grants and personal fees from Allergy Therapeutics Ltd. during the conduct of the study; personal fees from ALK, grants from ASIT biotech, personal fees from Allergopharma, grants and personal fees from Bencard, grants from Leti, grants, personal fees, and non-financial support from Lofarma, non-financial support from Roxall, grants and personal fees from Stallergenes, grants from Optima, personal fees from Friulchem, personal fees from Hexal, personal fees from Servier, personal fees from Klosterfrau, non-financial support from Atmos, personal fees from Bayer, non-financial support from Bionorica, personal fees from FAES, personal fees from GSK, personal fees from MSD, personal fees from Johnson&Johnson, personal fees from Meda, personal fees and non-financial support from Novartis, non-financial support from Otonomy, personal fees from Stada, personal fees from UCB, non-financial support from Ferrero, grants from Hulka, personal fees from Nuvo, grants and personal fees from Ursapharm, personal fees from Menarini, personal fees from Mundipharma, personal fees from Pohl-Boskamp, grants from Inmunotek, grants from Cassella-med GmbH & Co. KG, personal fees from Laboratoire de la Mer, personal fees from Sidroga, grants and personal fees from HAL BV, personal fees from Lek, personal fees from PRO-AdWise, personal fees from Angelini Pharma, grants and non-financial support from JGL, grants and personal fees from bitop, grants from Sanofi, grants and personal fees from Probelte Pharma, grants from Diater, personal fees from Worg Pharmaceuticals, outside the submitted work. S.B. reports about grants and/or personal fees as an advisor and for lectures from Bencard Allergie, Brain, Karl Storz, Altamira, Allergy Therapeutics, HAL Allergy, Allergopharma, ALK Abelló, Sanofi, Novartis, GSK, Astra Zeneca, MSD, Viatris, Ambu, Stryker, and the Federal Ministry of Education and Research. F.S., M.F.K., M.S., and P.J.d.K. are employees of Allergy Therapeutics (UK) Plc., and P.J.d.K., M.F.K., M.S. are named inventors on patents related to PQ Grass. The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.