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

Abstract

Allergen immunotherapy has been used for more than 100 y, but only recently underlying immunological mechanisms have started to be understood. New Allergy vaccines are now considered to be full pharmaceutical products, that should comply with general as well as specific pharmaceutical legal framework. GRAZAX® is the first global allergy vaccine developed in compliance with the new legal environment and is thus a reference for developing new allergy vaccines. Here, we provide a rationale description of GRAZAX®, providing a sequential description of its pharmaceutical and clinical development. With more than 25 clinical trials, involving more than 8000 patients, including as well three 5-y prospective clinical trials, GRAZAX® is a key product to understand the unique position of allergen-specific immunotherapy as a disease-modifying intervention.

Keywords: Grazax; allergen immunotherapy; allergy vaccine; grass allergy; sublingual immunotherapy.

Figure 1.

Scheme of the immunological response to allergen-specific immunotherapy (AIT). AIT during the early phase of the treatment (1–4 months), induces both mast cell desensitization and upregulation of Th2 response, mediated by high levels of IgE and IL4. During the active phase (1–3 y), a switch of isotype occurs. The levels of IgG4 increase while IgE significantly decrease. In this period is the maximum effect of IgG4 interference. Later, after 3 y of AIT treatment, in the post-therapy period, the regulatory response is established, and levels of IgE and IL4 are significantly decreased.

Figure 2.

Example of a 5-y prospective clinical trial design. GRAZAX® has three prospective 5-y studies on allergic rhinitis, asthma prevention, and immunological mechanisms.

Figure 3.

Clinical outcome of pivotal 5-y study. Magnitude of the effect is similar during active treatment period, as well as during 2-y follow-up. However, underlying immunological mechanisms (Figure 1) greatly vary over the years. Grey bars represent placebo and blue bars represent active treatment.

Figure 4.

Summary of clinical trials performed in Europe. GRAZAX® possesses the most complete and comprehensive clinical development programme ever performed in AIT.