Allergan reports positive results from Phase III Botox headache trials

In the two Phase III clinical trials, patients were randomly assigned to treatment with Botox or placebo injections every 12 weeks. The primary analysis was performed at week 24 following two treatment cycles. The two major efficacy measures evaluated in the trials were change from baseline in the number of headache episodes and number of headache days occurring in the 28 day-period preceding the week 24 time point.

In the first Phase III clinical trial, Allergan prospectively selected number of headache episodes as the primary endpoint for evaluation. Number of headache days was selected as the major secondary endpoint. Results from the first Phase III clinical trial indicated that although both the Botox and placebo treatment groups showed a statistically significant improvement from baseline, there was no significant difference in the reduction of number of headache episodes between patients receiving Botox and placebo.

However, the study showed a decrease in number of headache days, the FDA’s preferred efficacy measure, that was significantly greater in patients receiving Botox versus patients receiving placebo (p=0.006). The decrease in number of migraine and probable migraine days was also found to be significantly greater in patients treated with Botox versus patients receiving placebo (p=0.002).

Based on the data from the first Phase III clinical trial, the primary endpoint for the second Phase III study was prospectively changed to number of headache days, with number of headache episodes changed to a secondary endpoint, before the data were unmasked.

In the second Phase III study, the primary endpoint and key secondary endpoints showed statistically significant benefit of Botox treatment over placebo injections. Specifically, patients treated with Botox demonstrated a significantly greater decrease in both number of headache days (p<0.001) and number of headache episodes (p=0.003). Similar to the first Phase III trial, the second study also showed a decrease in number of migraine and probable migraine days that was significantly greater in patients treated with Botox versus placebo (p<0.001). In both Phase III clinical trials, Botox treatments were well tolerated in patients suffering from chronic migraine. Also, in both studies, quality of life was evaluated using the validated headache impact test. Importantly, patients receiving Botox treatments scored statistically significantly higher improvement in quality of life versus patients receiving placebo injections (p<0.001 in both studies). Based on this top-line analysis of its two Phase III clinical trials, Allergan hopes to file a supplemental biologics license application with the FDA for the use of Botox in chronic migraine by mid 2009. Full data results are expected to be published or presented by mid 2009.