Data showing safety and statistical significance relative to the efficacy endpoints in the study were presented at the 2006 annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) in Miami, Florida.
The phase II/III trial achieved its efficacy endpoint, namely the change from baseline in total nasal symptom scores (TNSS) during the peak period of the 2005 ragweed season for the Tolamba-treated group compared to the placebo group.
Secondary endpoints included TNSS change from baseline in the first season; ocular symptoms scores; nasal/ocular symptom scores; combined hayfever symptom scores; medication use (fexofenadine and pseudoephedrine) and safety.
Key results from the study, based on a final analysis of the available data to date, include the finding that patients treated with a single six-week course of Tolamba prior to the 2004 season experienced a statistically significant reduction in TNSS change from baseline during the two-week peak season compared to placebo-treated patients in the first and second years of the trial.
The group receiving a single course of Tolamba also achieved a statistically significant reduction in major secondary endpoints such as hay fever composite score. In addition, the safety profile of Tolamba was favorable. Systemic side effects were indistinguishable from placebo and there were no incidents of anaphylaxis.
However, in the arm of the trial in which subjects received a two-shot booster prior to the second (2005) season, statistical significance compared to placebo was not achieved relative to the primary endpoint or secondary endpoints.
At AAAAI, the trial’s principal investigator, Dr William Busse, discussed a hypothesis for the booster group’s results, suggesting that systemic boosting prior to the second season may alter lymphocyte trafficking that occurs following dosing in the first season. Boosting may redirect protective immune cells away from the nasal and ocular mucosa, to which they migrate during exposure to allergen in the first ragweed season, back to regional lymph nodes, where antigen (allergen) is being presented via systemic booster injection, thus reducing the number of potentially protective immune cells in the local environment.
As the company previously announced, Dynavax plans to conduct a Tolamba clinical trial designed to test a more intensive dosing regimen. This trial is anticipated to start by the beginning of Q2 2006 to take advantage of the 2006 ragweed season.