The protocols for the two studies 102 and 030 were reviewed and prospectively approved by the FDA under its special protocol assessment (SPA) procedure. Both studies achieved their primary endpoints.
Study 102 compared the efficacy of meal-time Afresa in combination with long-acting basal insulin versus twice daily injections of pre-mixed insulin in patients with type 2 diabetes. A total of 323 patients were randomized to the Afresa group and 331 patients were randomized to the pre-mix group.
Over the 52-week period of this study, A1C levels decreased comparably in the two treatment groups, 0.59 in the Afresa group and 0.71 in the pre-mix group. The 95% confidence interval (0.29%) of the between-group difference did not exceed the predetermined threshold of 0.40%, thereby establishing non- inferiority between Afresa and pre-mixed insulin.
Study 030 compared the pulmonary safety of meal-time inhalation of Afresa versus usual care. A total of 938 patients with type 1 and type 2 diabetes are expected to be randomized to the Afresa group; 951 patients were randomized to the comparator group. An additional 164 subjects without diabetes were enrolled into a third arm in order to assess the effect of diabetes on pulmonary function.
The primary endpoint of Study 030 was pre-specified with the FDA as a between-group difference (Afresa-treated versus comparator group) of less than 50ml per year in the decline from baseline measures of FEV1 over the entire study period. After two years of treatment, the difference between mean FEV1 values for the two treatment groups was 37ml (95% CI: 14-60 ml) – well within the 100ml pre-defined limit. Non-inferior results were also observed in secondary measures of lung function, including FVC, TLC and DLCo.
Peter Richardson, chief scientific officer of MannKind, said: We are continuing to analyze the results of our pivotal Phase III clinical studies, and plan to share more data in June 2009. In addition, we anticipate shortly the completion of the bioequivalency study that compares the clinical version of our inhaler to the more rugged and less costly commercial version. With this gating item behind us, we are now focusing on readying our new drug application for Afresa for submission to the FDA early in 2009.