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.
This Is Generex Biotechnology Pipeline Review
Antigen Express
Antigen Express is the fully owned life science subsidiary of Generex Biotechnology. Antigen Express is a platform and product-based company developing proprietary vaccine formulations for large, unmet medical needs. Their focus is on stimulating critical members of the immune response, known as T helper cells. The technology allows for antigen-specific stimulation or suppression of a T-helper response to virtually any antigen of known pathogenic potential. Antigen Express is building a deep pipeline of therapeutics aimed at a variety of major diseases, including cancer, infectious diseases and autoimmune-based syndromes.
Early efficacy analysis of the AE37 vaccine in a Phase II study
Click the logo to see the results for AE37 that were presented at the 2012 ASCO Breast Cancer Symposium
Peptide Vaccine Stimulates Immune Response in Patients With Breast Cancer
Click the logo to read about the results for AE37 that were presented at AACR 2012
Antigen Express President Dr Eric von Hofe
The President of Antigen Express is Dr Eric von Hofe, who has been impressive with advancing Antigen Express' pipeline and entering into smart collaborations. Dr. von Hofe joined Antigen Express in November of 2003. Prior to this time he held two positions at Millennium Pharmaceuticals; first as Program Director for Target Validation, where he presided over technology development efforts for Aventis and Cereon, and second as Director of Programs and Operations, Discovery Research. He received his Ph.D. from the University of Southern California and was a postdoctoral fellow at the University Hospital of Zurich and Harvard. From 1989 to 1992 he was Assistant Professor of Pharmacology at the University of Massachusetts Medical School. Click on the image of Dr von Hofe to read the abstract for his latest peer review article regarding cancer vaccines.
The AE37 Ii-Key synthetic peptide vaccine
Click on image to enlarge. Harvard scientists, who founded and lead Antigen Express, have pioneered and patented technology that modify MHC class II epitope peptides with a fragment of the MHC class II-associated invariant chain. Antigen Express recently reported interim results from a Phase II trial of the AE37 HER2/neu Ii-Key modified peptide vaccine for patients treated for breast cancer who are at high risk of relapse. While there was a 7% relapse rate in the control arm, there were no relapses in the Ii-Key peptide arm (AE37) when analyzed at the 13-month time point. A review article co-authored by Dr. Eric von Hofe, Ph.D., President of Antigen Express, entitled "A New Era in Anticancer Peptide Vaccines", will appear in an early 2010 edition of the journal Cancer, the International Interdisciplinary Journal published by the American Cancer Society. An advantage of using the type of active immunotherapy offered by AE37, as opposed to passive immunotherapy such as treatment with Herceptin, is that activated immune cells can detect and destroy cancer cells expressing much lower levels of HER-2/neu than is needed for recognition by Herceptin.
San Antonio Breast Cancer Symposium December 2009
Positive AE37 Phase II Interim results were reported at the San Antonio Breast Cancer Symposium in December 2009. Click the SABCS logo to view the poster presentation for AE37's Interim Phase II results, while the abstract text will be provided below.
Antigen Express' Ii-Key Peptide Vaccine Platform Technology
Click on the image for Antigen Express' pipeline to enlarge. AE37 is a novel peptide vaccine that is the product of a proprietary technology platform established at Antigen Express designed to increase the antigen-specific stimulation of CD4+ T helper cells. AE37 is capable of eliciting HER2/neu-specific immune responses, even without the use of an adjuvant. AE37 is the first peptide-based cancer vaccine to show potency in the absence of an immunoadjuvant.
Mary Crowely Cancer Research Center is Fully Funding the AE37 Combo Vaccine Study
Click on the Mary Crowley logo, provided above, to see the clinical trial listing for the AE37 Combo Vaccine
About Me
- Rich Steffens
- Rich Steffens has grown up in New Jersey, is a successful businessman, and studies social media trends amongst life science and biotech companies. His family is deeply influenced by the ill effects of diabetes. I am not qualified to offer investment or medical advice, and make no claims that I am an expert in these areas. I seek to share and learn.
The Future of Insulin Treatment
Dr Gerald Bernstein, Generex VP and former Pres of the ADA, was featured in an online video at the Doctor's Channel in a segment titled "Diabetes & Endocrinology Oral Insulin Delivery with Oral-Lyn". With many new insulin based drugs on the horizon, Dr Bernstein explains both the history of insulin treatment and what he believes to be the best future option- Oral-lyn. Click on the image of the current new insulin based drugs in development to view the video.
Oral-lyn's time profile; insulin only when a diabetic needs it, bringing less risk of hypoglycemia
This image, which you can click to enlarge, illustrates that with its very fast onset and offset of action, Oral-lyn buccal insulin spray may offer less risk of postprandial hypoglycemia as compared to conventional injected insulin therapy. Hypoglycemia is a life-threatening risk, and along with injections is the most important obstacle towards achieving good metabolic control. With each spray of the RapidMist device one unit of meal time Oral-lyn buccal insulin is said to be rapidly delivered into the bloodstream. The amount of sprays given is determined by the amount of insulin each unique diabetic requires to cover a meal. The company informs that the insulin only remains in the bloodstream during the time period the diabetic needs it, promising a safer and simpler approach.
The extended action of injectables may lead to hypoglycemia; the insulin often lingers too long
In this graph, which you can click to enlarge, we can see the long tail of both meal time analogues and regular insulin. Analogue prandial insulin is dosed approx 15 minutes before a meal, peaks in an hour, and with a duration of effect of 4 hours. Regular insulin is dosed 30 minutes before a meal, peaks in 2 hours and lingers up to 6 hours in the bloodstream. This slow acting tail activity often causes low blood sugar levels to occur after the glucose spike provided by the meal starts to decline. Generex states that Oral-lyn is taken right before the first bite of the meal, immediately begins to be absorbed in the inner lining of the mouth, peaks in 30 minutes, and blood sugar levels cleanly return to baseline within two hours. Generex finds there is no tail of activity with Oral-lyn as there is with all other forms of injectable insulin, so they believe the risk of postprandial hypoglycemia is greatly minimized. If blood levels are back at baseline after the meal, there is no reason to gorge on post meal snacks to offset any lingering insulin, which helps avoid unhealthy weight gain. The unique time action profile for Oral-lyn, if proven in the Phase III study, may provide greater flexibility in usage, as well as the ability to take small dose sprays before a snack when that tasty treat simply can not be resisted. Another main advantage for Oral-lyn may be its ability to mimic the first-phase insulin response seen in a healthy person. This first-phase insulin release is one of the first functions that people with diabetes lose. In healthy people our bodies release insulin within 10 minutes after eating.
Oral-lyn Buccal Insulin X-RAY imagery proves no deposition into the lungs
Unlike Mannkind's Afrezza, in which a powder insulin formulation is inhaled into and absorbed by the lungs, Oral-lyn is delivered as a fine spray to the buccal cavity by the RapidMist delivery system. Generex states the result is rapid insulin absorption through the buccal mucosal lining of the mouth without pulmonary (lung) exposure. The lungs, like all other vital organs in the body, are already a target of diabetes leading to lower lung function over time. The lungs are meant to process gasses, and not proteins. I think that Generex, via Oral-lyn buccal insulin, avoids potential pulmonary complications in a simpler and safer approach. Click on the provided X-Ray image to learn more.
Prandial insulin dosing is now as simple as a spray
Oral-lyn is available in a US FDA approved Treatment IND as well as in Phase III trials as a 1 UNIT per spray dose. For Oral-lyn, the delivery devise appears built to provide fine tuning post meal dosing. It appears as simple as taking another quick spray. In my opinion, as the safety concerns swirl around prospects for inhalable insulin, the Oral-lyn buccal insulin Treatment IND sounds like a great marketing advantage, since more and more diabetics and physicians will learn of buccal insulin as Generex works towards full approval.
Generex Oral-lyn Buccal Insulin
"Patients who are needle averse face a serious barrier to their recommended treatment," warns Generex "Generex Oral-lyn promises a pain-free alternative to injectable insulin, which is good news especially for older patients and children who find needles uncomfortable." Click on the image provided above to learn more about aversion to injections and diabetes.
Dr Gerald Bernstein, VP Medical Affairs Generex, former President of American Diabetes Association
Click on the photo of Dr Bernstein to view his interview on FOX Health. Dr Bernstein recently commented further on the unique safety profile for Oral-lyn: "It’s extremely safe by all the studies that have been done so far, including two years in animal tests. We haven’t seen allergic reaction. The lining of the mouth hasn’t shown any abnormalities. The buccal mucosa is an extra-tough and resilient tissue, it’s beaten up all the time. People bite themselves or burn themselves. Whatever doesn’t get absorbed is going to go to the stomach. Now the insulin molecule is unprotected and therefore it will be denatured by the acid and then broken down. There are no side effects." Dr Bernstein is an attending physician at Beth Israel Medical Center, and physician emeritus at Lenox Hill Hospital and Montefiore Medical Center, all in New York. He was formerly Director of the Beth Israel Health Care Systems Diabetes Management Program. Dr. Bernstein was president of the American Diabetes Association in 1998-99 and was for many years a member of the ADA's Board of Directors and its Executive Committee. He received the ADA's Banting Medal for Service in 1999. Dr. Bernstein presently serves on several ADA committees and on the Board of Directors of the American Diabetes Association Research Foundation.
Buccal Absorbtion
RapidMist Buccal Drug Delivery Device
