) today announced preliminary clinical results of two major trials using the Generex Oral-lyn™ formulation that will be used for registration and marketing. Unlike prior reported results from studies using older versions of the formulation, the combined data from the now completed 084 Trial in Type 1 patients and the Prevoral Trial in patients with Impaired Glucose Tolerance provide key insights into both the short-term pharmacokinetic and glucodynamic effectiveness of Generex Oral-lyn™ in reducing post-prandial increases in blood sugar as well as the long-term (one year) safety and positive effect on metabolic control using the registration formulation of Generex Oral-lyn™.
In the 084 Trial the final patient completed last visit in June providing 463 type 1 diabetes patients completing the study. The Prevoral trial had 31 patients with obesity and Impaired Glucose Tolerance (a pre-diabetes syndrome) completing the study.
Generex Oral-lyn™ was designed as a prandial (meal-time) insulin to replace the failing rapid secretion of insulin, which a healthy person's insulin secreting cells in the pancreas normally produce in response to eating a meal. While equally important in both type 1 and type 2 diabetes patients, this rapid release of insulin (first phase release) is one of the first abnormalities to occur in type 2 patients and in those individuals with pre-diabetes. The ability to reduce post meal hyperglycemia by replacing this first phase insulin release is key to providing glucose control in all patients with, or developing, diabetes mellitus. The reduction of postprandial hyperglycemia is even more important than the fasting blood glucose with respect to lowering the incidence of morbidity and mortality associated with the complications of diabetes.
The results of these two important trials are detailed below, but in summary confirm the following:
- Generex Oral-lyn™ demonstrated an increase in the circulating plasma insulin within the first 30 minutes of administration restoring first phase insulin response.
- Generex Oral-lyn™ did not result in elevated insulin levels at 2 and 3 hours after administration thus reducing the potential for post meal low blood sugar.
- Generex Oral-lyn™ reduced the rise in blood glucose by 1/3 at 2 hours and 1/4 at 3 hours demonstrating glycemic effectiveness and reducing risks associated with postprandial hyperglycemia.
- Generex Oral-lyn™ demonstrated a significant decrease in hemoglobin A1c in patients with IGT, and maintained HbA1c levels at baseline values in type 1 patients previously treated with injected insulin.
- Generex Oral-lyn™ was not associated with serious hypoglycemia or other significant adverse events, body weight changes, or development of insulin antibodies.
In the Prevoral Trial, with Professor Paolo Pozzilli as Chief Investigator, 31 subjects diagnosed with Impaired Glucose Tolerance (IGT), with a mean age of 52 years, and a body mass index of 33 (i.e. obese) received Generex Oral-lyn™ in equal doses before and 30 minutes after drinking 75 grams of glucose in a standard oral glucose tolerance test. Glucose and insulin levels were measured at baseline and 30, 60, 90, 120, and 180 minutes after consuming the glucose. Treatment with an aggregate of 12 Generex Oral-lyn™ sprays resulted in a 29.6% decrease in plasma glucose at two hours and a 26.8% decrease at three hours. Overall, the study found a mean reduction in glucose levels of 15.8%. Plasma insulin was also significantly increased at 30 minutes but not at 2 hours or 3 hours, demonstrating the important increase in first phase insulin availability. The lack of elevation of plasma insulin at 2 and 3 hours with Generex Oral-lyn™, in contrast to the elevations seen with injected insulin, reduces the potential for hypoglycemia (low blood sugar) to occur several hours after the meal.
When compared to placebo treatment, at 6 months, there was a significant reduction in hemoglobin A1c of -0.34 +/- 0.1% compared to an increase in the diet and exercise only group of +0.07 +/- 0.1%
Dr. James H. Anderson, Generex Senior Scientific Advisor, noted, "This study is the first demonstration of directly increasing first phase insulin levels and reducing post prandial glucose using a non-invasive therapy. The potential to use Generex Oral-lyn™ as a frontline treatment for patients with IGT could have far reaching implications. If such a non-invasive therapy delayed the onset of clinical diabetes along with all of its complications, it could eventually become a cost effective alternative to allowing the condition to progress with just diet and exercise instructional intervention."
Generex Oral-lyn™ clinical trial 084, conducted in 463 patients with type 1 diabetes, has been completed. Preliminary data from the final analyses clearly demonstrated that Generex Oral-lyn™ was effective in maintaining the hemoglobin A1c concentrations comparable to injected insulin during the 6-month head-to-head clinical trial. In addition, patients continuing on Generex Oral-lyn™ or transferred from injected insulin to Generex Oral-lyn™ after 6 months, did not lose metabolic control during the 6 month extension phase of the study despite the fact that their physician visit interval changed from every 4 weeks to every 3 months (a factor usually associated with less compliant behavior and loss of control in many clinical trials).
Poorly controlled patients (with HbA1c above 8.0) using Generex Oral-lyn™ for the entire 12 months had an HbA1c of 8.3% at baseline and 8.2% at 12 months. Those patients originally randomized to injected insulin, who had an HbA1c of 7.7% at start of Generex Oral-lyn™ therapy, had an HbA1c of 7.8% at study completion. Well-controlled patients (with average baseline HbA1c less than 6.5) using Generex Oral-lyn™ had less than a 0.2% difference in HbA1c compared to those randomized to insulin for the first six months. Those insulin treated patients placed on Generex Oral-lyn™ therapy at 6 months had no change in HbA1c from their baseline to study end. There were no serious hypoglycemic events or other adverse events attributable to Generex Oral-lyn™. In conclusion, in patients with type 1 diabetes, Generex Oral-lyn™ demonstrated safety and comparability to injected insulin across a broad range of levels of metabolic control.
Dr. Gerald Bernstein, VP of Medical Affairs for Generex Biotechnology, commented, "Both of these studies confirm the value of Generex Oral-lyn™ in the two major types of diabetes. For people with Type 1 there is an opportunity to replace or supplement bolus injections affording greater compliance in reaching their goals. For the millions of people with Pre-diabetes it provides an additional tool to control postprandial glucose and delay the clinical onset of Type 2 diabetes and reduce the risk for complications. All of this will help alleviate the enormous economic burden of diabetes.
Generex Biotechnology Corporation