The following abstract pertaing to an Oral-lyn study with subjects suffering fgrom impaired glucose tolerance will be presented at the 48th EASD Annual Meeting on October 3rd, 2012 in Berlin, Germany:
Title: Buccal spray insulin in subjects with impaired glucose tolerance: improvement in HbA1c is lost after 6 months wash out therapy
Presentation Time: Wednesday, Oct 03, 2012, 2:30 PM - 2:45 PM
Authors: A. Palermo1, N. Napoli1, E. Maddaloni1, A. Lauria1, A. Soare1, S. Manfrini1, M. Altomare2, S. Leotta2, P. Pozzilli1;
1University campus Bio medico, Roma, Italy, 2Hospital "S.Pertini", Roma, Italy.
Abstract: Background and aims: subjects who develop type 2 diabetes (TD2) pass through a phase of impaired glucose tolerance (IGT). Defects in the action or secretion of insulin are the two major abnormalities leading to development of glucose intolerance. Resistance to insulin progressively increases when passing from normal glucose tolerance through IGT to diabetes, whereas secretion of insulin gradually decreases. Glucose tolerance is assumed to remain normal as long as the beta cell secretion can compensate for insulin resistance. IGT will develop only when insulin secretion fails to compensate fully for such resistance, resulting in postprandial hyperglycaemia that is linked to an increased risk for cardiovascular disease even though there is no progression to diabetes. Many intervention trials have been conducted in IGT patients but only one aimed to decrease post prandial hyperglycaemia. Our previous proof of concept study in subjects with IGT undergoing a prolonged OGTT demonstrated that treatment with 12 puffs of buccal spray insulin was followed by a significant 29.6% decrease in mean plasma glucose at two-hours and a 26.8% decrease at three-hours. Based on these findings a short trial with buccul spray insulin was planed.
Materials and methods: We have designed a randomized controlled trial in patients with IGT comparing a 6 months duration therapy using buccal spray insulin (12 puffs per meal) plus physical exercise and diet (treatment group A, n=16, HbA1c at entry 6.2% + 0.4) vs physical exercise and diet only (control group B, n=16, HbA1c at entry 6.0% + 0.3). Primary endpoint of this study is the reduction of HbA1c of 0.3 % at 6 month treatment between experimental versus control group. Secondary endpoints include the evaluation of antibodies against insulin (IA), changes in body weight, number of hypoglycaemic events during the treatment period and the evaluation of metabolic control at 6 months after the end of the treatment. HbA1c levels, metabolic parameters and insulin antibodies were measured at baseline, at 3 months up to 6 months followed by 6 months wash out.
Results: Subjects treated with buccal spray insulin achieved a significant reduction of HbA1c compared to the control group ([[unable to display character: ∆]] HbA1c 0’- 6 months -0.3% vs +0.09% p= 0.002). At 6 months after the end of treatment, in group A HbA1c levels raised from 5.8 % + 0.3 to 6.1 + 0.5 resulting in loss of previous achieved improvement of metabolic control and 19% of the treated patients developed TD2 ( vs 6% in the control group). There was no significant difference in body weight and no hypoglycaemic or other adverse events were observed during the study period in both groups. No generation of IA was observed in subjects with IGT treated with buccal spray insulin.
Conclusion: These results indicate that buccal spray insulin is an effective treatment compared to diet + physical exercise in patients with IGT in reducing HbA1c without adverse effects. However the beneficial effects of buccul spray insulin is lost within few months of suspension of treatment. A larger trial is required to demonstrate the long term effects of this buccul spray insulin in preventing TD2 in subjects with IGT.
Supported: Educational grant from Generex Biotechnology
This is the oddest study abstract that I have ever read. If the investigator substitutes Oral-lyn with any other prandial insulin, or another glucose lowering drug, the study will illustrate that beneficial effects of the insulin or drug is lost within a few hours after discontinuation of treatment, never mind six months later.
Showing posts with label diabetes. Show all posts
Showing posts with label diabetes. Show all posts
Sunday, July 22, 2012
Sunday, June 26, 2011
Generex Takes Part at the American Diabetes Association's Scientific Sessions
The American Diabetes Association's Scientific Sessions takes place from June 24 - 28. Generex is an exhibitor at ADA 2011, and an Oral-lyn abstract has been accepted to be presented at this prestigious industry event.
The image is of Generex's exhibition booth at ADA 2011, courtesy of Generex's Todd Falls. Click the image to enlarge. The abstract being presented at ADA 2011 highlights final six month data from a Phase II study with IGT subjects, or prediabetics, which may present a paradigm change in how they are treated. The following is the abstract from the event:
According to data from the 2011 National Diabetes Fact Sheet, 79 million people in the U.S. have prediabetes (IGT). As obesity rates rise, so does the need to medically treat this group when the current recommendations of diet and exercise fall short. We have learned in recent weeks that the ongoing Phase III study in Type 1 patients has reached a protocol approved amount of subjects, and will be closed to new recruits. Final data may be available by the end of the year.
We now see positive Phase II results in IGT subjects, and plans to intitiate a Phase III study in Type 2 patients, anticipated to be completed by the end of 2013. A much broader label is being pursued for Oral-lyn, beyond Type 1's, whom make up only 10% of the US insulin market. With no adverse events reported in any studies, or cited as a concern in recent FDA guidance, Oral-lyn represents the next big thing that the current market does not understand.
The image is of Generex's exhibition booth at ADA 2011, courtesy of Generex's Todd Falls. Click the image to enlarge. The abstract being presented at ADA 2011 highlights final six month data from a Phase II study with IGT subjects, or prediabetics, which may present a paradigm change in how they are treated. The following is the abstract from the event:
Treatment of Impaired Glucose Tolerance with Buccal Spray Insulin: A 6 Months Randomised Controlled Trial
Abstract No:
2224-PO
Author(s): ANDREA PALERMO, NICOLA NAPOLI, ERNESTO MADDALONI, ANGELO LAURIA, SILVIA MANFRINI, MARIA ALTOMARE, SERGIO LEOTTA, PAOLO POZZILLI
Location(s):
Rome, Italy
Abstract Body: In patients with impaired glucose tolerance (IGT), upon implementation of life style changes and metformin, a third returns to normal glucose tolerance, a third continues with IGT and the rest goes on to develop clinical type 2 diabetes. An increased risk for cardiovascular disease occurs in the latter two groups even though there is no progression to diabetes. A previous proof of concept study demonstrated that treatment with 12 puffs of buccal spray insulin was followed by a significant 29.6% decrease in mean plasma glucose at two-hours and a 26.8% decrease at three-hours.
We have designed a randomized controlled trial in patients with IGT comparing buccal spray insulin (Ora-lyn) (12 puffs per meal) plus physical exercise and diet (treatment group A, n=16, HbA1c at entry 6.06% + 0.5) vs. physical exercise and diet only (control group B, n=16, HbA1c at entry 5.9% + 0.3). HbA1c levels, metabolic parameters and insulin antibodies were measured at baseline and every 3 months up to 6 months. Primary endpoint is the reduction of HbA1c of 0.3% at 6 month treatment between the experimental and the control group. Secondary endpoints include the evaluation of antibodies against insulin (IA), changes in body weight and number of hypoglycaemic events.
Subjects treated with buccal spray insulin achieved a significant reduction of HbA1c compared to the control group (Δ HbA1c 0'- 6 month -0.34%+0,1 vs +0.07%+ 0,1 p =0,03). There was no significant difference in body weight and no hypoglycaemic or other adverse events were observed during the study period in both groups. No generation of IA was observed in subjects with IGT treated with buccal spray insulin.
These preliminary results indicate that buccal spray insulin is an effective treatment compared to diet + physical exercise in patients with IGT in reducing HbA1c without adverse effects. A larger trial is required to demonstrate the long term effects of this therapy. Here is the link.
According to data from the 2011 National Diabetes Fact Sheet, 79 million people in the U.S. have prediabetes (IGT). As obesity rates rise, so does the need to medically treat this group when the current recommendations of diet and exercise fall short. We have learned in recent weeks that the ongoing Phase III study in Type 1 patients has reached a protocol approved amount of subjects, and will be closed to new recruits. Final data may be available by the end of the year.
We now see positive Phase II results in IGT subjects, and plans to intitiate a Phase III study in Type 2 patients, anticipated to be completed by the end of 2013. A much broader label is being pursued for Oral-lyn, beyond Type 1's, whom make up only 10% of the US insulin market. With no adverse events reported in any studies, or cited as a concern in recent FDA guidance, Oral-lyn represents the next big thing that the current market does not understand.
Thursday, December 9, 2010
Generex Taps Former Eli Lilly Senior Medical Director to Strengthen Clinical and Regulatory Efforts for Oral-lyn
"Having worked with the Generex team in the fledgling stage of Generex Oral-lyn development while at Eli Lilly, I believed then that the product had the potential to become a first-in-class therapeutic insulin treatment even though the companies ultimately headed in different directions as is often the case with early stage collaborations." - Dr. James H Anderson Jr on December 9, 2010
Generex Biotechnology (GNBT) announced on Thursday the appointment of Former Eli (LLY) Lilly Senior Medical Director Dr. James H. Anderson, Jr., MD, FFPM, FACE to the company's Scientific Advisory Board. While such news is not often met with much fanfare, there is an unique element to this announcement when considering the history between Generex and Eli Lilly. A look back may help us realize where we are today as we wait for Oral-lyn's future to unfold.
In September 2000, Generex and Eli Lilly entered into a Development and License Agreement for Oral-lyn buccal insulin. In May 2003, the companies mutually agreed to end the deal. During that two and a half year time period, Lilly did not conduct a single clinical trial to assess either the safety or efficacy of Generex's buccal insulin, while they were actively spending their resources developing the AIR inhaled insulin system, as part of a developmental agreement with Alkermes (ALKS) that was signed in 2001. Lilly had held rights to separate buccal and inhalable insulin programs, and like many large pharmas at the time, they were placing their bet that inhalable insulin was the right path to take.
Like clowns jumping into the same car, many pharma companies were competing with one another to develop inhalable forms of insulin. Pfizer, with partner Nektar (NKTR) Therapeutics, led the foray, and in 2006 they were the first inhalable insulin to win FDA approval. The Exubera story is well known, and I won't repeat the entire saga. Pfizer's failure to earn commercial success with Exubera led to their costly decision in late 2007 to abandon the product and return rights to Nektar. Pfizer recorded a $2.8 billion pretax hit on the product, one of the drug industry's costliest failures. Industry giant Novo (NVO) Nordisk followed Pfizer's lead, and in January 2008 they decided to end development of the AERx inhaled insulin system while the product was deep into costly Phase III testing.
Later in 2008, Lilly terminated their agreement with Alkermes to develop inhalable insulin. Their first quarter results for that year reveal the asset impairment and exit costs associated with betting on the wrong non-invasive insulin to be $132.6 million. Today's news reminds me that sometimes large pharma places the wrong bet, and in this case quite a few found themselves racing down the same dead end. Mannkind is the sole surviving biotech developing a promising form of inhalable insulin, they have a PDUFA date for Afrezza inhalable insulin later this month. This comes after they received a Complete Response Letter a few months ago. Their product offers definite advantages over the failed inhalable insulins such as Exubera, and I actually have come to hope they succeed so diabetics later have greater choices for administering their required insulin.
While thinking of all the money the large pharmas lost while following each other into development of inhalable insulin, I recall a quote attributed to Generex representative Todd Falls in 2003 after Lilly terminated their agreement to develop buccal insulin. He remarked at the time that Lilly "didn't want to put the money into us. Lilly felt, I guess, they had some other interests, and didn't want to be the lead on the project." That decision didn't work out very well for Lilly, and Generex is still here with Oral-lyn being studied in a worldwide Phase III trial, and conditionally approved by the FDA in the first Treatment IND awarded to a diabetes drug.
I continue to believe that Oral-lyn, a tasteless liquid aerosol mist formulation that is administered to the buccal mucosa using a proprietary delivery system, has many advantages over inhalable and injectable forms of insulin, although they must be further proven in the Phase III study. These include the small and simple hand held metered dose device, significantly lowered risk of postprandial hypoglycemia, lack of insulin resistance amongst subjects, an actual decrease in Body Mass Index, with no absorption into the lungs. One spray equals one unit of meal time insulin, and this provides greater flexibility in usage, as well as the ability to take small dose sprays before a snack when a treat simply can not be resisted. The unique time action profile for Oral-lyn may be its greatest advantage, with its ability to mimic the first-phase insulin response seen in a healthy person.
Dr James H Anderson was involved with Oral-lyn when Eli Lilly held developmental rights, and has returned all these years later to talk so optimistically about its development. His statement that he believed even then that Oral-lyn had the potential to become a first-in-class therapeutic insulin treatment even though the companies ultimately headed in different directions helps erase doubt formed by the demise of the deal between the two companies. Since we know that Lilly did not conduct a single test to evaluate Oral-lyn, we can see that a business decision was made void of negative data and full of faulty strategy. Dr Anderson is surely needed to assist Generex, and his background is proven. After all, he was a key player in getting Lilly's blockbuster Lispro approved. That is the type of experience the team at Generex needs to help get Oral-lyn to the finish line.
As Generex continues to align the company with expert talent to strengthen the company's clinical/regulatory efforts, the news always strikes me as sort of a validation of the state of the pipeline. New additions to the Scientific Advisory Board, such as Amgen (AMGN) co-founder Dr Joseph Rubinfeld, Pfizer's (PFE) Vice President of Strategic Alliances and Partnerships Dr Craig Eagle, and now Former Eli Lilly Senior Medical Director Dr. James H. Anderson Jr, also have their own reputations on the line, yet they are quoted making remarks that speak volumes about the hidden worth of Oral-lyn, as well as the company's immunotherapeutic cancer vaccines. Generex's faithful shareholders sure hope some of that hidden worth soon comes into vision.
Generex Biotechnology (GNBT) announced on Thursday the appointment of Former Eli (LLY) Lilly Senior Medical Director Dr. James H. Anderson, Jr., MD, FFPM, FACE to the company's Scientific Advisory Board. While such news is not often met with much fanfare, there is an unique element to this announcement when considering the history between Generex and Eli Lilly. A look back may help us realize where we are today as we wait for Oral-lyn's future to unfold.
In September 2000, Generex and Eli Lilly entered into a Development and License Agreement for Oral-lyn buccal insulin. In May 2003, the companies mutually agreed to end the deal. During that two and a half year time period, Lilly did not conduct a single clinical trial to assess either the safety or efficacy of Generex's buccal insulin, while they were actively spending their resources developing the AIR inhaled insulin system, as part of a developmental agreement with Alkermes (ALKS) that was signed in 2001. Lilly had held rights to separate buccal and inhalable insulin programs, and like many large pharmas at the time, they were placing their bet that inhalable insulin was the right path to take.
Like clowns jumping into the same car, many pharma companies were competing with one another to develop inhalable forms of insulin. Pfizer, with partner Nektar (NKTR) Therapeutics, led the foray, and in 2006 they were the first inhalable insulin to win FDA approval. The Exubera story is well known, and I won't repeat the entire saga. Pfizer's failure to earn commercial success with Exubera led to their costly decision in late 2007 to abandon the product and return rights to Nektar. Pfizer recorded a $2.8 billion pretax hit on the product, one of the drug industry's costliest failures. Industry giant Novo (NVO) Nordisk followed Pfizer's lead, and in January 2008 they decided to end development of the AERx inhaled insulin system while the product was deep into costly Phase III testing.
Later in 2008, Lilly terminated their agreement with Alkermes to develop inhalable insulin. Their first quarter results for that year reveal the asset impairment and exit costs associated with betting on the wrong non-invasive insulin to be $132.6 million. Today's news reminds me that sometimes large pharma places the wrong bet, and in this case quite a few found themselves racing down the same dead end. Mannkind is the sole surviving biotech developing a promising form of inhalable insulin, they have a PDUFA date for Afrezza inhalable insulin later this month. This comes after they received a Complete Response Letter a few months ago. Their product offers definite advantages over the failed inhalable insulins such as Exubera, and I actually have come to hope they succeed so diabetics later have greater choices for administering their required insulin.
While thinking of all the money the large pharmas lost while following each other into development of inhalable insulin, I recall a quote attributed to Generex representative Todd Falls in 2003 after Lilly terminated their agreement to develop buccal insulin. He remarked at the time that Lilly "didn't want to put the money into us. Lilly felt, I guess, they had some other interests, and didn't want to be the lead on the project." That decision didn't work out very well for Lilly, and Generex is still here with Oral-lyn being studied in a worldwide Phase III trial, and conditionally approved by the FDA in the first Treatment IND awarded to a diabetes drug.
I continue to believe that Oral-lyn, a tasteless liquid aerosol mist formulation that is administered to the buccal mucosa using a proprietary delivery system, has many advantages over inhalable and injectable forms of insulin, although they must be further proven in the Phase III study. These include the small and simple hand held metered dose device, significantly lowered risk of postprandial hypoglycemia, lack of insulin resistance amongst subjects, an actual decrease in Body Mass Index, with no absorption into the lungs. One spray equals one unit of meal time insulin, and this provides greater flexibility in usage, as well as the ability to take small dose sprays before a snack when a treat simply can not be resisted. The unique time action profile for Oral-lyn may be its greatest advantage, with its ability to mimic the first-phase insulin response seen in a healthy person.
Dr James H Anderson was involved with Oral-lyn when Eli Lilly held developmental rights, and has returned all these years later to talk so optimistically about its development. His statement that he believed even then that Oral-lyn had the potential to become a first-in-class therapeutic insulin treatment even though the companies ultimately headed in different directions helps erase doubt formed by the demise of the deal between the two companies. Since we know that Lilly did not conduct a single test to evaluate Oral-lyn, we can see that a business decision was made void of negative data and full of faulty strategy. Dr Anderson is surely needed to assist Generex, and his background is proven. After all, he was a key player in getting Lilly's blockbuster Lispro approved. That is the type of experience the team at Generex needs to help get Oral-lyn to the finish line.
As Generex continues to align the company with expert talent to strengthen the company's clinical/regulatory efforts, the news always strikes me as sort of a validation of the state of the pipeline. New additions to the Scientific Advisory Board, such as Amgen (AMGN) co-founder Dr Joseph Rubinfeld, Pfizer's (PFE) Vice President of Strategic Alliances and Partnerships Dr Craig Eagle, and now Former Eli Lilly Senior Medical Director Dr. James H. Anderson Jr, also have their own reputations on the line, yet they are quoted making remarks that speak volumes about the hidden worth of Oral-lyn, as well as the company's immunotherapeutic cancer vaccines. Generex's faithful shareholders sure hope some of that hidden worth soon comes into vision.
Subscribe to:
Posts (Atom)
