|>>VALENCIA, Calif., Dec. 22 /PRNewswire-FirstCall/ -- MannKind Corporation (Nasdaq: MNKD - News) released summary information today on results from its US-based, late Phase 2 clinical study of Technosphere® Insulin, a pulmonary insulin formulation delivered via its proprietary inhaler to patients with diabetes mellitus. The MannKind pulmonary insulin system rapidly delivers regular human insulin to the bloodstream in a manner that approximates the first phase insulin release spike by the pancreas that occurs almost immediately after the start of a meal in normal, healthy individuals but is lost in patients who develop diabetes. This spike plays an important role in glucose control by signaling the liver to stop releasing glucose into the bloodstream while glucose is being ingested from a meal.|
The double-blind, placebo-controlled study was conducted at 21 sites in the United States. Patients who participated in the study were experiencing inadequate control of diabetes determined on the basis of HbA1c results (a measure of glucose control over the preceding three to four months) obtained at the time of screening. All patients received basic diabetes education and performed regular monitoring of blood glucose levels at home prior to randomization. A total of 123 patients (41 women and 82 men) were randomized into either a group that inhaled Technosphere Insulin (doses containing 6 to 48 units of insulin) or Technosphere placebo, in both cases at mealtimes. One hundred seven patients completed the full 12 weeks of treatment with blinded study agents.
Patients that constituted the primary efficacy population (n=90) had a mean HbA1c level of 7.74% at baseline with a range of 6.6% to 10.5%. As part of the study analysis plan, these patients were evaluated in two groups: those with moderately severe elevations of HbA1c levels at baseline of 8.0% and above (values identified by the American Diabetes Association as requiring definitive therapeutic intervention to minimize complications) and those with mild- to moderate elevations of HbA1c levels at baseline ranging from 6.6% to 7.9%.
Patients with moderately severe elevations of HbA1c levels at baseline (n=35; mean HbA1c 8.72%; range 8.0% to 10.5%), who were treated with Technosphere Insulin, experienced a mean reduction of 1.37 percentage points by the end of 12 weeks of treatment. The difference in reduction of HbA1c levels between the Technosphere Insulin and the placebo treatment groups was highly statistically significant (p=0.0007) in favor of Technosphere Insulin.
Patients with mild to moderate elevations of HbA1c levels at baseline (n=55; mean HbA1c 7.18%; range 6.6% to 7.9%), who were treated with Technosphere Insulin, experienced a mean reduction of 0.43 percentage points by the end of 12 weeks of treatment. The difference in reduction of HbA1c levels between the Technosphere Insulin and the placebo treatment groups was statistically significant (p=0.0447) in favor of Technosphere Insulin.
Overall, in the primary efficacy population, there was a highly statistically significant difference between the two treatment groups (in favor of the Technosphere Insulin group) with respect to the proportion of patients who achieved a reduction in HbA1c levels by the goal of at least 0.6 percentage points (chi-square; p=0.0052). Approximately four times as many patients in the Technosphere Insulin-treated group achieved a final HbA1c level of 6.5% or less as compared to the placebo-treated group.
There were no serious adverse events that were related to the use of the study drug. No episodes of severe hypoglycemia occurred in any of the patients treated with Technosphere Insulin. Pulmonary function was assessed by DLco measurements, FVC and FEV1 rates, and there was no clinically significant difference between the 12-week test results and baseline values in the patient group receiving Technosphere Insulin. Importantly, there was also no evidence of treatment-induced insulin antibodies occurring in patients treated with Technosphere Insulin.
Dr. Wendell Cheatham, Corporate Vice President and Chief Medical Officer of MannKind, commented, "This study indicates that Technosphere Insulin can effectively lower blood glucose levels in patients with type 2 diabetes who previously were experiencing inadequate control of their disease. The typical risks of frequent or severe hypoglycemia associated with insulin therapy appear to be minimal with Technosphere Insulin, giving it a potentially significant safety advantage over other therapies."
Alfred Mann, Chairman and Chief Executive Officer of MannKind, stated further, "In our earlier clinical studies, we observed that the kinetic profile of Technosphere Insulin approximates the first phase insulin release spike of normal, healthy individuals. With these latest observations of no increases in antibodies, no clinically significant changes in pulmonary function and no episodes of severe hypoglycemia in patients treated with Technosphere Insulin, we continue to be optimistic regarding the future of Technosphere Insulin. We are now preparing to submit these results to the United States Food and Drug Administration. In the meantime, we have initiated our first Phase 3 clinical trial in Europe, enrolling patients this week. We are pleased that the Company continues to achieve its intended milestones on or ahead of schedule."<<
Hmmm. No antibdies is good, beats competing inhalables; but otherwise, results are just like everyone else's, maybe even a little inferior. And this trial compares to a technosphere placebo, not to a s.c. insulin cohort. I assume they'll have to use a more robust comparison in PIII, but no details of that trial are given. Hmmm. As to pulmonary function, they deviate from using statistical significance and tlak of clinical significance. Hmmm.