GRAZAX®: a sublingual immunotherapy vaccine for Hay fever treatment: from concept to commercialization

References

• Bonertz A, Roberts GC, Hoefnagel M, Timon M, Slater JE, Rabin RL, Bridgewater J, Pini C, Pfaar O, Akdis C, Goldstein J. Challenges in the implementation of EAACI guidelines on allergen immunotherapy: a global perspective on the regulation of allergen products. Allergy. 2018;73:64–76. doi:10.1111/all.13266.
   PubMed Web of Science ®Google Scholar
• Bonertz A, Roberts G, Slater JE, Bridgewater J, Rabin RL, Hoefnagel M, Timon M, Pini C, Pfaar O, Sheikh A, Ryan D. Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: an analysis from the EAACI AIT guidelines project. Allergy. 2018;73:816–26. doi:10.1111/all.13357.
   PubMed Web of Science ®Google Scholar
• Ohashi-Doi K, Kito H, Du W, Nakazawa H, Ipsen H, Gudmann P. Bioavailability of house dust mite allergens in sublingual allergy tablets is highly dependent on the formulation. Int Arch Allergy Immunol. 2017;174:26–34. doi:10.1159/000479693.
   PubMed Web of Science ®Google Scholar
• Brimnes J, Kildsgaard J, Jacobi H, Lund K. Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis. Clin Exp Allergy. 2007;37:488–97. doi:10.1111/j.1365-2222.2006.02624.x.
   PubMed Web of Science ®Google Scholar
• van Ree R, Chapman MD, Ferreira F, Vieths S, Bryan D, Cromwell O, et al. The CREATE project: development of certified reference materials for allergenic products and validation of methods for their quantification. Allergy. 2008;63:310–26. doi:10.1111/j.1398-9995.2007.01612.x.
   PubMed Web of Science ®Google Scholar
• Kaul S, Zimmer J, Dehus O, Constanzo A, Daas A, Buchheit KH, et al. Validation of ELISA methods for quantification of the major birch allergen Bet v 1 (BSP090). Pharmeur Bio Sci Notes. 2017;2017:69–87.
   PubMedGoogle Scholar
• Römmelmayer ALL, Larsen JN. GRAZAX®: an oromucosal vaccine for treating grass pollen allergy with immunotherapy. In: Jorgensen L, Nielsen HM, editors. Delivery technologies for biopharmaceuticals: peptides, proteins, nucleic acids and vaccines; 2009.
   Google Scholar
• Berings M, Karaaslan C, Altunbulakli C, Gevaert P, Akdis M, Bachert C, Akdis CA. Advances and highlights in allergen immunotherapy: on the way to sustained clinical and immunologic tolerance. J Allergy Clin Immunol. 2017;140:1250–67. doi:10.1016/j.jaci.2017.08.025.
   PubMed Web of Science ®Google Scholar
• Rosace D, Gomez-Casado C, Fernandez P, Perez-Gordo M, Dominguez MDC, Vega A, Belver MT, Ramos T, Vega F, Marco G, et al. Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling. J Allergy Clin Immunol. 2019;143:681–90 e1. doi:10.1016/j.jaci.2018.03.013.
   PubMed Web of Science ®Google Scholar
• Suarez-Fueyo A, Ramos T, Galan A, Jimeno L, Wurtzen PA, Marin A. Grass tablet sublingual immunotherapy downregulates the TH2 cytokine response followed by regulatory T-cell generation. J Allergy Clin Immunol. 2014;133(130–8):e1–e2. doi:10.1016/j.jaci.2013.09.043.
   Google Scholar
• Varona R, Ramos T, Escribese MM, Jimeno L, Galan A, Wurtzen PA, Vega F, Marín A, Martín S, Carrera AC, Blanco C. Persistent regulatory T-cell response 2 years after 3 years of grass tablet SLIT: links to reduced eosinophil counts, sIgE levels, and clinical benefit. Allergy. 2019;74:349–60. doi:10.1111/all.13553.
   PubMed Web of Science ®Google Scholar
• Scadding GW, Calderon MA, Shamji MH, Eifan AO, Penagos M, Dumitru F, et al. Effect of 2 years of treatment with sublingual grass pollen immunotherapy on nasal response to allergen challenge at 3 years among patients with moderate to severe seasonal allergic rhinitis: the grass randomized clinical trial. Jama. 2017;317:615–25. doi:10.1001/jama.2016.21040.
   PubMed Web of Science ®Google Scholar
• Guideline on the clinical development on products for specific immunotherapy for the treatment of allergic diseases. Doc. Ref. CHMP/EWP/18504/2006. © European Medicines Agency, 2008. 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK.
   Google Scholar
• Ibanez MD, Kaiser F, Knecht R, Armentia A, Schopfer H, Tholstrup B, Bufe A. Safety of specific sublingual immunotherapy with SQ standardized grass allergen tablets in children. Pediatr Allergy Immunol. 2007;18:516–22. doi:10.1111/j.1399-3038.2007.00556.x.
   PubMed Web of Science ®Google Scholar
• Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2006;117:802–09. doi:10.1016/j.jaci.2005.12.1358.
   PubMed Web of Science ®Google Scholar
• Rak S, Yang WH, Pedersen MR, Durham SR. Once-daily sublingual allergen-specific immunotherapy improves quality of life in patients with grass pollen-induced allergic rhinoconjunctivitis: a double-blind, randomised study. Qual Life Res. 2007;16:191–201. doi:10.1007/s11136-006-9110-3.
   PubMed Web of Science ®Google Scholar
• Aberer W, Hawranek T, Reider N, Schuster C, Sturm G, Kranke B. Immunoglobulin E and G antibody profiles to grass pollen allergens during a short course of sublingual immunotherapy. J Investig Allergol Clin Immunol. 2007;17:131–36.
   PubMed Web of Science ®Google Scholar
• Dahl R, Stender A, Rak S. Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis. Allergy. 2006;61:185–90. doi:10.1111/j.1398-9995.2005.00949.x.
   PubMed Web of Science ®Google Scholar
• Dahl R, Kapp A, Colombo G, de Monchy JG, Rak S, Emminger W, Riis B, Grønager PM, Durham SR. Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years. J Allergy Clin Immunol. 2008;121:512–8 e2. doi:10.1016/j.jaci.2007.10.039.
   PubMed Web of Science ®Google Scholar
• Durham SR, Emminger W, Kapp A, de Monchy JG, Rak S, Scadding GK, Wurtzen PA, Andersen JS, Tholstrup B, Riis B, et al. SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J Allergy Clin Immunol. 2012;129:717–25 e5. doi:10.1016/j.jaci.2011.12.973.
   PubMed Web of Science ®Google Scholar
• Bufe A, Eberle P, Franke-Beckmann E, Funck J, Kimmig M, Klimek L, Knecht R, Stephan V, Tholstrup B, Weisshaar C, et al. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol. 2009;123:167–173.e7. doi:10.1016/j.jaci.2008.10.044.
   PubMed Web of Science ®Google Scholar
• Maloney J, Bernstein DI, Nelson H, Creticos P, Hébert J, Noonan M, Skoner D, Zhou Y, Kaur A, Nolte H. Efficacy and safety of grass sublingual immunotherapy tablet, MK-7243: a large randomized controlled trial. Ann Allergy Asthma Immunol. 2014;112:146–153.e2. doi:10.1016/j.anai.2013.11.018.
   PubMed Web of Science ®Google Scholar
• Hebert J, Blaiss M, Waserman S, Kim H, Creticos P, Maloney J, Kaur A, Li Z, Nelson H, Nolte H. The efficacy and safety of the Timothy grass allergy sublingual immunotherapy tablet in Canadian adults and children. Allergy Asthma Clin Immunol. 2014;10:53. doi:10.1186/1710-1492-10-41.
   PubMed Web of Science ®Google Scholar
• Nolte H, Casale TB, Lockey RF, Fogh BS, Kaur A, Lu S, Nelson HS. Epinephrine Use in Clinical Trials of Sublingual Immunotherapy Tablets. J Allergy Clin Immunol Pract. 2017;5:84–9 e3. doi:10.1016/j.jaip.2016.08.017.
   PubMed Web of Science ®Google Scholar
• Maloney J, Berman G, Gagnon R, Bernstein DI, Nelson HS, Kleine-Tebbe J, Kaur A, Li Q, Nolte H. Sequential treatment initiation with timothy grass and ragweed sublingual immunotherapy tablets followed by simultaneous treatment is well tolerated. J Allergy Clin Immunol Pract. 2016;4:301–9 e2. doi:10.1016/j.jaip.2015.11.004.
   PubMed Web of Science ®Google Scholar
• Reich K, Gessner C, Kroker A, Schwab JA, Pohl W, Villesen H, Wüstenberg E, Emminger W. Immunologic effects and tolerability profile of in-season initiation of a standardized-quality grass allergy immunotherapy tablet: a phase III, multicenter, randomized, double-blind, placebo-controlled trial in adults with grass pollen-induced rhinoconjunctivitis. Clin Ther. 2011;33:828–40. doi:10.1016/j.clinthera.2011.06.006.
   PubMed Web of Science ®Google Scholar
• Schwab JA, Wolf H, Schnitker J, Wustenberg E. Safety and tolerability of an intra-seasonal initiation of the SQ-standardised grass allergy immunotherapy tablet: a non-interventional observational study investigating the feasibility during routine administration. Clin Drug Investig. 2013;33:719–26. doi:10.1007/s40261-013-0115-8.
   PubMed Web of Science ®Google Scholar
• Schwab JA, Wolf H, Schnitker J, Wustenberg E. Intra-seasonal initiation of the SQ-standardised grass allergy immunotherapy tablet routinely applied by allergy specialists and general practitioners with experience in treatment of allergy: a non-interventional observational study. Pulm Ther. 2018;4:45–57. doi:10.1007/s41030-018-0050-1.
   PubMedGoogle Scholar
• Alesina R, Milani M, Pecora S. A multicenter, randomized, parallel-group trial assessing compliance, tolerability, safety, and efficacy to treatment with grass allergy tablets in 261 patients with grass pollen rhinoconjunctivitis. J Allergy (Cairo). 2012;2012:673502.
   PubMedGoogle Scholar
• Calderon MA, Birk AO, Andersen JS, Durham SR. Prolonged preseasonal treatment phase with Grazax sublingual immunotherapy increases clinical efficacy. Allergy. 2007;62:958–61. doi:10.1111/j.1398-9995.2007.01416.x.
   PubMed Web of Science ®Google Scholar
• Nelson H, Blaiss M, Nolte H, Wurtz SO, Andersen JS, Durham SR. Efficacy and safety of the SQ-standardized grass allergy immunotherapy tablet in mono- and polysensitized subjects. Allergy. 2013;68:252–55. doi:10.1111/all.12074.
   PubMed Web of Science ®Google Scholar
• Valovirta E, Berstad AK, de Blic J, Bufe A, Eng P, Halken S, Ojeda P, Roberts G, Tommerup L, Varga EM, et al. Design and recruitment for the GAP trial, investigating the preventive effect on asthma development of an SQ-standardized grass allergy immunotherapy tablet in children with grass pollen-induced allergic rhinoconjunctivitis. Clin Ther. 2011;33:1537–46. doi:10.1016/j.clinthera.2011.09.013.
   PubMed Web of Science ®Google Scholar
• Zuberbier T, Bachert C, Bousquet PJ, Passalacqua G, Walter Canonica G, Merk H, Worm M, Wahn U, Bousquet J. GA(2) LEN/EAACI pocket guide for allergen-specific immunotherapy for allergic rhinitis and asthma. Allergy. 2010;65:1525–30. doi:10.1111/j.1398-9995.2010.02474.x.
   PubMed Web of Science ®Google Scholar
• GINA. Global Strategy for Asthma Management and Prevention 2006. Global Initiative for Asthma – GINA. Fontana, WI 53125, USA. https://ginasthma.org/
   Google Scholar
• Bacharier LB, Boner A, Carlsen KH, Eigenmann PA, Frischer T, Gotz M, Helms PJ, Hunt J, Liu A, Papadopoulos N, et al. Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. Allergy. 2008;63:5–34. doi:10.1111/j.1398-9995.2007.01586.x.
   PubMed Web of Science ®Google Scholar
• Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63(Suppl 86):8–160. doi:10.1111/j.1398-9995.2007.01620.x.
   PubMed Web of Science ®Google Scholar
• Valovirta E, Petersen TH, Piotrowska T, Laursen MK, Andersen JS, Sorensen HF, et al. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy. J Allergy Clin Immunol. 2018;141:529–38 e13. doi:10.1016/j.jaci.2017.06.014.
   PubMed Web of Science ®Google Scholar
• Malling HJ, Lund L, Ipsen H, Poulsen L. Safety and immunological changes during sublingual immunotherapy with Standardized Quality grass allergen tablets. J Investig Allergol Clin Immunol. 2006;16:162–68.
   PubMed Web of Science ®Google Scholar
• Kleine-Tebbe J, Ribel M, Herold DA. Safety of a SQ-standardised grass allergen tablet for sublingual immunotherapy: a randomized, placebo-controlled trial. Allergy. 2006;61:181–84. doi:10.1111/j.1398-9995.2006.00959.x.
   PubMed Web of Science ®Google Scholar
• Calderon M, Essendrop M. Specific immunotherapy with high dose SO standardized grass allergen tablets was safe and well tolerated. J Investig Allergol Clin Immunol. 2006;16:338–44.
   PubMed Web of Science ®Google Scholar
• Nelson HS, Nolte H, Creticos P, Maloney J, Wu J, Bernstein DI, Wu J, Bernstein DI. Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults. J Aller Clin Immunol. 2011;127:72–80. doi:10.1016/j.jaci.2010.11.035.
   PubMed Web of Science ®Google Scholar
• Blaiss M, Maloney J, Nolte H, Gawchik S, Yao R, Skoner DP. Efficacy and safety of timothy grass allergy immunotherapy tablets in North American children and adolescents. J Allergy Clin Immunol. 2011;127:64–71. doi:10.1016/j.jaci.2010.11.034.
   PubMed Web of Science ®Google Scholar
• Poole CD, Bannister CA, Andreasen JN, Andersen JS, Currie CJ. Estimation of health-related utility (EQ-5D index) in subjects with seasonal allergic rhinoconjunctivitis to evaluate health gain associated with sublingual grass allergen immunotherapy. Health Qual Life Outcomes. 2014;12:99. doi:10.1186/1477-7525-12-99.
   PubMed Web of Science ®Google Scholar
• Horn A, Zeuner H, Wolf H, Schnitker J, Wustenberg E. Health-related quality of life during routine treatment with the sq-standardised grass allergy immunotherapy tablet: a non-interventional observational study. Clin Drug Investig. 2016;36:453–62. doi:10.1007/s40261-016-0388-9.
   PubMed Web of Science ®Google Scholar
• Blanco C, Bazire R, Argiz L, Hernandez-Pena J. Sublingual allergen immunotherapy for respiratory allergy: a systematic review. Drugs Context. 2018;7:212552. doi:10.7573/dic.212552.
   PubMedGoogle Scholar
• Lund K, Kito H, Skydtsgaard MB, Nakazawa H, Ohashi-Doi K, Lawton S. The importance of tablet formulation on allergen release kinetics and efficiency: comparison of freeze-dried and compressed grass pollen sublingual allergy immunotherapy tablet formulations. Clin Ther. 2019;15:S0149–S2918.
   Google Scholar
• Duffort O, Quintana J, Ipsen H, Barber D, Polo F. Antigenic similarity among Group 1 allergens from Grasses and Quantitation ELISA using monoclonal antibodies to Phl p 1. Int Arch of Allergy and Immunol. 2008;145:283–90. doi:10.1159/000110887.
   PubMed Web of Science ®Google Scholar
• Johansen N, Weber RW, Ipsen H, Barber D, Broge L, Hejl C. Extensive IgE cross-reactivity towards the Pooideae grasses substantiated for a large number of grass-pollen.sensitized subjects. Int Arch Allergy Immunol. 2009;150:325–34. doi:10.1159/000226233.
   PubMed Web of Science ®Google Scholar
• Cromwell O, Niederberger V, Horak F, Fiebig H. Clinical experience with recombinant molecules for allergy vaccination. Curr Top Microbiol Immunol. 2011;352:27–42.
   PubMed Web of Science ®Google Scholar
• Batard T, Sanjuan A, Denis L, Nguyen H, Montagut A, Sastre J, Rak S, Cuiné JF. Two grass pollen tablets commercially available for allergy immunotherapy display different IgE epitope repertoires. Clin Transl Allergy. 2019;27:13.
   Google Scholar
• Eguiluz-Gracia I, Tay TR, Hew M, Escribese MM, Barber D, O’Hehir RE, Torres MJ, Torres MJ. Recent developments and highlights in biomarkers in allergic diseases and asthma. Allergy. 2018;73:2290–305. doi:10.1111/all.13628.
   PubMed Web of Science ®Google Scholar
• Barber D, Escribese MM. Predictive biomarkers in allergen specific immunotherapy. Allergol Immunopathol. 2017;45(Suppl 1):12–14. doi:10.1016/j.aller.2017.09.003.
   PubMedGoogle Scholar