Welcome to Pipeline Review

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.

Search This Blog

Monday, November 8, 2010

The Tehran Study of Insulin Buccal Spray (Oral-Lyn) efficacy in Type 1 Diabetes

Insulin Buccal Spray (Oral-Lyn) efficacy in Type 1 Diabetes

Zohreh Annabestani1, Sasan Sharghi1, Samimeh Shahbazi1, Seyed Sajad Mohseni Salehi Monfared1, Farzaneh Karimi1, Eghbal Taheri1,
Ramin Heshmat1, Bagher Larijani1

1-Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Iran

Background: To determine efficacy and side effects of oral insulin spray (Oral-Lyn) in comparison to subcutaneously injected regular human insulin.

Methods: Fifteen patients with type 1 diabetes entered in this open-label single arm study with historical control of the same patients for 8 weeks conducted at the Endocrine and Metabolism Research Institute (EMRI). Some biochemical and hormonal lab tests were taken before and at the end of the study. All patients used Oral-Lyn spray instead of regular insulin in dinner time and peripheral glucose measurements were self-monitored by them via similar type glucometer in four different times included fasting, two hours after breakfast, before dinner and two hours post dinner time blood glucose measures.

Results: This study demonstrated that buccal spray had not serious complications and had the same effects on blood glucose control in comparison with regular insulin injections. Also, the rate of hypoglycemia was decreased to 33.3% at the end of the study from 50% at the beginning. Hemoglobin A1C (HbA1c) values did not show any significant changes throughout the study.

Conclusion: Oral-Lyn provides similar postprandial glucose control and caused lower hypoglycemic episodes when compared to regular insulin injections.

Conventional injection insulin therapy is recognized to be inconvenient due to multiple daily injections. As we know, insulin is a large peptide molecule that might be absorbed from gastrointestinal tract, but it rapidly degraded in acidic gastric condition. Many efforts have been performed to deliver insulin via oral roots. So, a rapid-acting, orally administrated recombinant human insulin formulation (Oral-Lyn, Generex Biotechnology, Toronto, ON, Canada) has been identified to improve absorption properties in compare with subcutaneous injection of human regular insulin, but with an earlier maximum effect and a shorter duration of action (1, 2).

In the present study, buccal spray insulin was administrated to patients with type 1 diabetes to determine its efficacy in lowering blood glucose levels and evaluation of possible side effects in compare with subcutaneous regular insulin at mealtime.

This was an open-label single-arm study with historical control of the same patients for eight weeks since May to November 2009 which involved 15 patients with type 1 diabetes (12 males and 3 females). All the participants received information about the purpose of the study, procedures, and possible side effects of buccal spray, in detail. Screening evaluations included physical examinations and clinical and laboratory tests before study recruitment. Also, we questioned about the history of previous hypoglycemic episodes.

Inclusion criteria were at least 1-year history of type 1 diabetes mellitus, which is currently managed with daily insulin injections totaling 0.3 to 0.8 IU/kg of body weight. Their HbA1c should be greater than 6.5 % and less than or equal to 9.5%. Exclusion criteria were oral lesions and/or disease involving the oral cavity. They should not have history of severe hypoglycemia with seizure or coma within the past 6 months. All the participants underwent training about how to use an identical placebo spray device to avoid improper using of the device. Moreover, all the patients were given a certain glucometer device to check their blood glucose at different 4 times included fasting blood sugar (FBS), 2 hours post breakfast (2hpp), and specially before dinner and 2 hours after throughout the study period. We assigned a visit session one week before the recruitment for adjusting the dose of regular insulin injection and Oral-Lyn spray puffs. Each puff was considered as one unit insulin. Oral-Lyn was considered in divided doses with 50% of the dose before the meal and the rest after the meal as recommended. We just substituted regular insulin in dinner time with Oral-Lyn and regular insulin in the morning and lunch times were unchanged. We assigned some visits to collect information about any new problem or side effect and results of self-monitored blood glucose values recorded by the patients. Before start and at the end of the study, the participants were evaluated for some laboratory tests included: cell blood count (CBC), HbA1c, lipid profile, liver enzymes, blood urea nitrogen (BUN) and serum Creatinine (Cr), 24 hours urine protein and microalbumin values. The study protocol was approved by the Ethics Committee of Endocrine and Metabolism Research Institute of Tehran University of Medical Sciences and all the participants signed informed consent.

Insulin which administered via the buccal root was well-tolerated in all the patients. No serious complication was observed among the patients; nonetheless just one patient had bleeding gum that was in case of dropouts. Two patients had mouth numbness and one of them reported vertigo which lasted no longer and had no serious sequel (Table 1). More than 50% of the patients at the beginning of the study reported hypoglycemia episodes and this rate decreased to 33.3% at the end of the study (Table 2).

Mean glucose values before dinner and 2 hours after the dinner at start and at the end of the study has shown in Table 2. Also, this Table shows that the mean values of patients' weight were not changed throughout the study. Mean values of HbA1c did not significantly change throughout the study period. There were no changes in hormonal and biochemical lab test values except Creatinine which was raised in patients at the end of the study (Table 3).

Our study showed that Oral-Lyn provided similar postprandial glucose control in patients with type 1 diabetes comparing with regular insulin. Also, it caused lower hypoglycemic episodes when compared to regular insulin injections. Hypoglycemia rates decreased from 54% to 33% as evidenced by our results which suggest that lesser risk of hypoglycemia is expected by using this root of insulin delivery; although it was not statistically significant due to low sample size, it seems clinically meaningful. As we know, the pharmacokinetic properties of Oral-Lyn have been found to be similar to that of rapid-acting regular insulin in patients with type 1 and type 2diabetes (1-4). The Oral-Lyn peptide has some advantages such as rapid absorption, no need for injection, and decrease postprandial hyperglycemia. Also, this formulation causes no major complication or discomfort in the mouth as we observed in our study and is rapidly absorbed within 5-10 min which is faster than subcutaneous injected regular insulin. Although, our results derived from a small number of patients, which considered our study limitation, it was revealed that insulin delivered via oral root at mealtime could be considered as an acceptable substitute for regular insulin injections.

This project was financially supported by Sinamode Pars organization. The link for the above study can be found here.