Stallergenes plays a major role in the research & development of desensitisation pharmaceuticals specialities 

With an R&D budget currently represents 16% of sales, Stallergenes is making constant progress in the development of desensitisation treatments. These are tested to a level equivalent to that of symptomatic treatments and come under the regulatory field of pharmaceutical specialities.

The development programme for sublingual desensitisation tablets

This program is a major project for Stallergenes and represents significant progress in terms of treatment for patients suffering from allergic respiratory diseases. It consists of developing and marketing a sublingual desensitisation tablet as a pharmaceutical speciality.

The sublingual desensitisation tablet program includes three products, indicated for the treatment of allergic rhinitis caused by the most common allergens:

Grasses tablet for sublingual desensitisation The Grasses tablet for sublingual desensitisation, for which efficacy and tolerance have been validated by the results of a Phase IIb/III clinical trial involving more than 600 patients and completed in 2005, have been registered with the German authorities, in June 2008. Based on the positive results of the paediatric pivotal study (VO52), Stallergenes have applied for a paediatric extension of the product's indications. Stallergenes have launched the product in the adult indication on the German market. The company expects to extend this launch to the paediatric population this year so as to capture the forthcoming prescription period for grass pollen desensitisation in both indications. Subsequent market authorization in Europe will be applied afterwards through a Mutual Recognition Procedure (MRP) for both indications, Germany being the reference member state. The clinical development programme has already enrolled around 1600 patients to date. A long term pivotal study is proceeding according to schedule, and is currently in its second year. The company plans to file two INDs for adult and paediatric trials with the FDA this year. Alongside these phase III studies, Stallergenes has set up a pharmacodynamics study (VO 56) in a centre equipped with a pollen chamber, so that results will be unaffected the variable nature of the pollen season. The study will enable an evaluation of the onset of action of the tablet on rhino-conjunctivitis symptoms with a view to optimizing treatment schedules. In asscoiation with this pharmacodynamics study, research is being carried out into biomarkers for the immune response and possible correlations with the clinical response.

Bet v 1 tablet for sublingual desensitisation The Bet v 1 tablet for sublingual desensitisation (major allergen of birch pollen) is the first desensitisation tablet developed from an allergen obtained by genetic engineering. This approach enables the production of fully characterised and quantifiable products. The purity and stability of recombinant allergens guarantees perfect reproducibility at a consistent level of quality. Two adult phase I studies have enabled us to establish to a high degree of accuracy the target dose for the continuation of development. A phase II study to determine dosage on the basis of efficacy and tolerance criteria for the tablet will begin in 2008 with about 500 patients in Europe using precoseasonal administration.

Mites tablet for sublingual desensitisation The desensitisation tablet indicated for the treatment of allergy to mites , is made up of a mixture of allergenic extracts of D. pteronyssinus and D. farinae, which are the cause of this condition in most European patients. Following the results of the Phase I trial carried out in 2005, demonstrating good tolerance of this Mites tablet, a Phase II/III trial with adults, involving more than 600 patients, is being conducted in 10 European countries. On the same development model as for the grass pollens, in the event of the adult pivotal study being successful, a phase III paediatric extension study and a phase III adult confirmation study will also be initiated in the United States. The adult programme will continue in Europe with a study of treatment schedule optimization and the long term efficacy of the product. 

 
At the same time as the development program for sublingual desensitisation tablets, Stallergenes' Research and Development teams are carrying out an ambitious project for the design of a second-generation therapy.

The objective is to develop a sublingual desensitisation tablet for mites allergies that is even more effective, enabling more rapid action with reduced doses.

The combination of molecular biology techniques and formulation/adjuvant strategies enables better targeting of the immune system of the sublingual mucosa and improvement of the efficacy of desensitisation treatments. The "Enhanced Allergens" programme is based on this concept.

In particular, this program aims to develop a sublingual desensitisation treatment for house dust mite allergies, on the basis of recombinant proteins. This second generation treatment associates recombinant allergens presented in the form of a fusion protein with formulation/adjuvantation strategies. This combination enables better recognition of the allergen by the immune system, thereby improving the efficacy of desensitisation treatments. Understanding of specific immune responses to the allergen in the oral mucosa has considerably improved in recent years, enabling the development of new sublingual treatments. This work has confirmed that the oral immune system will preferentially induce a state of tolerance in response to the allergen.

Stallergenes has initiated another ambitious research project, as part of the "Enhanced Allergens" programme. The project consists of identifying biomarkers¹ that could be used to measure the clinical efficacy of desensitisation treatments. More specifically, the identification of such biomarkers will ultimately :

• facilitate the clinical development of desensitisation treatments ;
• improve immunisation schedules, and dosage ;
• enable the identification of "responsive"patients for whom treatment will be effective.

Data relating to clinical immunotherapy studies, and natural protective responses observed in healthy individuals that are exposed to allergens will enable the identification of such biomarkers that can then be used to create even more effective desensitisation treatments.

(1) A biomarker is a biological parameter in which a qualitative or quantitative change enables the prediction of a response, in particular the clinical response, to a product.

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