Generex Provides Preliminary Results of Generex Oral-lyn Clinical Trials in Patients with Type 1 Diabetes and Patients with Impaired Glucose Tolerance
WORCESTER, Mass. and TORONTO, July 8, 2011 /PRNewswire/ -- Generex Biotechnology Corporation (OTC Bulletin Board: GNBT) (www.generex.com) 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% (p=0.03). There was no significant difference in body weight change and no hypoglycemic or other adverse events were observed during the study period in either group. No generation of insulin antibodies was observed in the subjects treated with Generex Oral-lyn™.
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.
About Generex Biotechnology Corporation
Generex is engaged in the research, development, and commercialization of drug delivery systems and technologies. Generex has developed a proprietary platform technology for the delivery of drugs into the human body through the oral cavity (with no deposit in the lungs). The Company's proprietary liquid formulations allow drugs typically administered by injection to be absorbed into the body by the lining of the inner mouth using the Company's proprietary RapidMist™ device. The Company's buccal insulin spray product, Generex Oral-lyn™ is in Phase III clinical trials at several sites around the world. Antigen Express, Inc. is a wholly owned subsidiary of Generex. The core platform technologies of Antigen Express comprise immunotherapeutic vaccines for the treatment of malignant, infectious, allergic, and autoimmune diseases. Antigen Express has pioneered the use of specific CD4+ T helper stimulation in immunotherapy. One of its platform technologies relies on inhibition of expression of the Ii protein. Antigen Express scientists, and others, have shown clearly that suppression of expression of the Ii protein in cancer cells allows for potent stimulation of T helper cells and prevents the further growth of cancer cells.
Cautionary Note Regarding Forward-Looking Statements
This release and oral statements made from time to time by Generex representatives in respect of the same subject matter may contain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements can be identified by introductory words such as "expects," "plan," "believes," "will," "achieve," "anticipate," "would," "should," "subject to" or words of similar meaning, and by the fact that they do not relate strictly to historical or current facts. Forward-looking statements frequently are used in discussing potential product applications, potential collaborations, product development activities, clinical studies, regulatory submissions and approvals, and similar operating matters. Many factors may cause actual results to differ from forward-looking statements, including inaccurate assumptions and a broad variety of risks and uncertainties, some of which are known and others of which are not. Known risks and uncertainties include those identified from time to time in the reports filed by Generex with the Securities and Exchange Commission, which should be considered together with any forward-looking statement. Risks and uncertainties relating to the proposed reverse stock split include the risks that (1) Generex will not meet the standards for listing its common stock on a national stock exchange; and (2) Generex will not meet or sustain the minimum share price requirement of a national stock exchange. No forward-looking statement is a guarantee of future results or events, and one should avoid placing undue reliance on such statements. Generex undertakes no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Generex cannot be sure when or if it will be permitted by regulatory agencies to undertake additional clinical trials or to commence any particular phase of clinical trials. Because of this, statements regarding the expected timing of clinical trials or ultimate regulatory approval cannot be regarded as actual predictions of when Generex will obtain regulatory approval for any "phase" of clinical trials or when it will obtain ultimate regulatory approval by a particular regulatory agency. Generex claims the protection of the safe harbor for forward-looking statements that is contained in the Private Securities Litigation Reform Act.
SOURCE Generex Biotechnology Corporation
Posted: July 2011