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Generex Biotechnology, and their wholly owned subsidiary Antigen Express, are developing promising new drugs to treat diabetes, as well as synthetic peptide vaccines targeting HER2/neu cancer and pandemic flu. The flagship product for Generex is Oral-lyn buccal insulin. Antigen Express' leading vaccine is the AE37 HER2/neu synthetic peptide vaccine to prevent breast cancer recurrence. I am not qualified to offer investment or medical advice, and make no claims that I am an expert in these areas. I am a layman and a shareholder in this company. The left side of Pipeline Review holds blogs regarding Generex and Antigen Express, while the right side offers items of due diligence mixed with my analysis which may be of interest to others seeking to learn about Generex's pipeline. If the left side only shows the latest blog, click on the word home to view them all.

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Thursday, March 4, 2010

Previously Reported Oral-lyn Buccal Insulin Study Results

Buccal Spray Insulin for the Management of Post-Prandial Hyperglycaemia in Subjects with Impaired Glucose Tolerance

Results: Postprandial hyperglycemia (PPHG) occurs as the consequence of a reduced early insulin response after a meal and has been linked with an increased risk of cardiovascular events and raised mortality risk. Subjects with PPHG often present with dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction and markers of inflammation.

The objective of this phase II study was to investigate the safety and efficacy of treatment with buccal spray insulin (Generex Oral-lyn™) on post-prandial plasma glucose excursions and insulin levels in subjects with impaired glucose tolerance (IGT). A total of 15 Caucasian subjects, mean age 50.1 ±13.7 SD years, 10 females and 5 males with IGT were included in the study. Subjects were randomized to take 4, 6 or 12 Generex Oral-lyn™ puffs, split in two doses each, before and 30 minutes after a standard 75 gr oral glucose tolerance test (OGTT). Glucose excursions and insulin levels were measured at baseline and at 30, 60, 90, 120, 180 min.

There were no significant differences in glucose levels during OGTT with 4 or 6 U.I. doses compared to baseline OGTT. Treatment with 12 Units was followed by a significant 31.2% decrease in mean plasma glucose (mg/dl) at two-hours (from 179.0± 10.9 to 124.0±42.8, p=0.01) and a 28.4% decrease at three-hours (from 126.8±55.1 to 86.5±24.8, p=0.04). Considering all time points of OGTT, there was a mean reduction of 16.5% in plasma glucose levels. There was a trend for increased insulin (µU/L) levels at all measurements reaching statistical significance at 30 min (from 59.6±17.2 to 76.4±18.2, p=0.04). No adverse events were observed during the study period.

In conclusion, this proof of concept study demonstrates that treatment with buccal spray insulin is a simple and valuable therapy for PPHG in subjects with IGT.

A 12 week phase IV study of (Oral-lyn aka Oral Recosulin in India) recombinant human regular insulin metered dose buccal spray on subjects with type 2 diabetes who are suboptimally controlled while on oral antidiabetic agents

Background: Evidence suggests that early insulin therapy for glycemic
control provides additional benefits over conventional therapy in DM. However, subcutaneous route of administration is a barrier to initiating early insulin-therapy in majority of these patients. Postprandial glucose control by buccal route of insulin administration may overcome this barrier, improve glycemic control and provide further benefits.

Objective: This prospective open label phase IV multicentric study in India evaluated efficacy and safety of insulin metered dose buccal spray (Generex-Oral-lyn; Oral RecosulinTM) given pre- and post-meal in adult subjects with Type 2 DM that are suboptimally controlled with oral anti-diabetic agent(s).

Recombinant human regular insulin metered dose buccal spray (Generex Oral-lyn™ ; Oral RecosulinTM) appears to be well tolerated and highly preferred by patients. The detail data and its finding will be presented in the meeting. Interpretation and conclusions: Treatment with insulin metered dose buccal spray (Generex Oral-lyn™; Oral RecosulinTM) in type 2 diabetes mellitus patients on OHA, resulted in glycemic improvement and was well tolerated. Oral Recosulin had high acceptability in patients.

Insulin Analogue (Basal + Pre-Prandial Injection) vs. Human Insulin (Basal Injection + Prandial Oral Insulin (Generex Oral-lyn™) in Type-1 Diabetes Mellitus: A 372-Day Comparison

Results: This report is of Phase-3 of a 585-day study at which over than 45,000 daily pre-meal glucose measurements, and 2-week Fructosamine (Fruc) and Glycated Hemoglobin (HbA1c) determinations were obtained. Stabilization Phase-1 and First Comparison Phase-2 results were previously reported.

Briefly, 26 subjects were allocated to Two Cohorts of 13 subjects each for a 372-day Comparison. Control Cohort (CC) subjects received Basal Once a Day subcutaneous (s.c). glargine insulin-analogue and Pre-meal s.c. lispro insulin analogue. Treated Cohort (TC) subjects received Basal twice daily sc-isophane insulin (NPH) + Meal time Generex Oral-lyn™.

For HbA1c, Fruc and mean pre-prandial glucose, the levels were significantly lower in TC cohort (P<0.001 regardless of whether parametric or non-parametric tests were employed). A regimen consisting of basal BID s.c. NPH and prandial orally-absorbed regular insulin (Generex Oral-lyn™) attained lower pre-meal glucose, HbA1c and Fru concentrations, than a regimen using basal and pre-prandial insulin analogue injections in Type-1 DM during a 372-day period.

Comparison of Pre-prandial s.c. Regular Insulin vs Prandial Oral Insulin in Adult Type-1 DM Subjects Receiving Basal s.c. Twice Daily Isophane Insulin

Results: Participating subjects were 25 Type-1 DM subjects (17M; 8F); Age 28.6y (9.0); Height 164.8cm (8.53); Weight 62.4kg (8.68); BMI 22.9 (1.97); BMI 23.8 (2.0). Duration of DM 9.7 (5.1) years. Stabilization period: All subjects received standard therapy (ST) with basal s.c. twice daily (BID) isophane insulin (BID-NPH) and 3 pre-prandial s.c. injections of regular insulin (TID-RI). Subsequent to SP subjects were allocated to 2 cohorts: Control Group (CG): 11 subjects (5M; 6F); Treated Group (TG): 14 subjects (14M; 2F). Subjects in CG continued receiving BID-NPH and TID-RI.

Subjects in CG continued receiving BID-NPH and TID-RI. Subjects in the TG received BID-NPH and TID prandial split doses of Oral Insulin (Generex Oral-lynTM -OI). Comparison Phase (CP) lasted 99 days. Fructosamine (F) and Glycated Hemoglobin (HbA1c) were determined every 14 days.

After SP, 25 adult Type-1 DM subjects underwent a 99-day CP. Near normalization of parameters of DM metabolic control was achieved in all subjects. Direct comparison of HbA1c concentrations during CP demonstrate a superior effect of Generex Oral-lyn™ over subcutaneously injected regular insulin.

6-Month Safety and Efficacy of Lunch-Time Oral Insulin in Juvenile Type-1 DM Subjects Receiving Basal Glargine Insulin and Pre-Breakfast and Pre-Dinner S.C. Regular Insulin

Results: Adolescence in DM is associated with changes that make metabolic control difficult and injection at lunch time is frequently missed; therefore, replacement of lunch-time injection with oral insulin (Generex Oral-lynTM) was studied.

Participants were 24 adolescents (12M; 12F) and 5 young adult (2M; 3F) Type-1 DM subjects. Age 15.7y(3.0); Height 155.1cm(10.2); Weight 53kg(10.8); BMI 21.9(3.0); DM duration 6.8 (2.6). Stabilization period with Standard therapy (ST): s.c. BID insulin analogue + 3 pre-prandial s.c. regular insulin injections (RI). Comparison Phase: 28 days of ST; thereafter, split doses of Generex Oral-lynTM replaced lunch-time injection of RI for 6 months.

At study end, 6 independent evaluators blinded to biochemical results assessed compliance using a 9-parameter method. 21 subjects had good compliance (GC); 8 subjects had very poor compliance (PC). GC score: 51.86 (14.97) vs. PC score 14 (10.87) p<0.001. 29 nine juvenile Type-1 DM subjects replaced lunch-time dose of regular insulin with Generex Oral-lynTM for 6 months. Metabolic control depended on compliance.