Allergic rhinitis - Tolamba
There has been a dramatic rise in the incidence of allergic conditions in recent years, possibly as a result of the increase in cleanliness in the developed world meaning the immune systems of children receive fewer of the challenges that build up antibodies. It is thought that this may result in an increased Th-2 biased immune response, and a decrease in the Th-1 response.
There has been a dramatic rise in the incidence of allergic conditions in recent years, possibly as a result of the increase in cleanliness in the developed world meaning the immune systems of children receive fewer of the challenges that build up antibodies. It is thought that this may result in an increased Th-2 biased immune response, and a decrease in the Th-1 response.
Allergen-specific immunotherapy to build up antibodies against allergens has been in clinical use for decades, but frequent, large doses are needed, and there is also the danger that the allergic response they provoke will cause problems in itself. A potential alternative is the use of DNA-based immunotherapeutics that induce at Th-1 biased response and prevent Th-2 responses, and there is evidence that conjugates of the allergen with immunostimulatory oligodeoxynucleotides could be both safer and more effective.
Dynavax has been working on just such a product, designed to prevent seasonal allergic rhinitis caused by ragweed. It combines the ragweed pollen allergen, Amb a 1, and an immunostimulatory phosphorothioate oligodeoxynucleotide with the aim of producing a potent, specific Th-1 biased immune response.1
Several clinical trials have been carried out. A randomised, placebo-controlled Phase I study was run in the middle of winter to avoid any exposure to pollen, and 19 subjects who were allergic to ragweed were given six subcutaneous injections of 0.06 0.3, 1.2, 3.0, 6.0 and 12µg of Tolamba or placebo.2 Those given the active had lower Th-2 immunity and higher Th-1 immunity at both two and 16 weeks after the last injection.
Another study was carried out in 57 allergic patients before the ragweed season began.3 A similar dosing regimen, or placebo, was given weekly for six weeks. During the following ragweed season, no difference was seen between the two groups; however, the year after those given Tolamba had fewer nasal and chest symptoms.
Its efficacy was also investigated in a randomised, double blind, placebo-controlled Phase II study in 25 patients.4 Subjects were either given the six week schedule or placebo before the ragweed season, and monitored during it and the subsequent two seasons. In the first, the treated group had better peak season rhinitis and nasal symptom scores, and also better mid-season quality of life scores. Better scores were reported again the year after.
A second Phase II trial looked at its efficacy over two seasons in a much larger group of 462 adults.5 This time, the weekly doses before the first season were 1.2, 3.0, 6.0, 15. 21 and 30µg, and the placebo group contained histamine; before the second season, the treated group were given two weekly doses of 3.0 and 30µg. Tolamba gave a long lasting improvement in symptoms, and trials continue.