Biocon's oral insulin Tregopil formerly referred to as IN-105 has successfully completed its phase 1 studies which validate and provide the basis for the next phase of clinical development of this important molecule.

Based on the positive data, the company has decided to take this research into the next phase of clinical trials for validation in a larger patient cohort. The clinical studies on insulin Tregopil, which were conducted in the US under a US IND, were initiated in partnership with Bristol-Myers Squibb (BMS) prior to their divestment of the diabetes franchise to AstraZeneca.

The key research outcomes of the phase 1 study conducted in the US has indicated that the assay accurately differentiates between endogenous insulin and insulin Tregopil in human plasma and thereby enables the assessment of pharmacokinetic effects of insulin Tregopil.

A drug-drug interaction study of insulin Tregopil and metformin showed that metformin does not affect its efficacy.

The food effect studies using the specific assay for Insulin Tregopil showed that high carbohydrate, high protein and high fat diets do not affect the efficacy of Insulin Tregopil.

Dosing studies conducted with meals show that there is a clear linear relationship between the dose of administered insulin Tregopil and the decrease in postprandial glucose excursion rates.

“These studies show that the oral delivery of insulin is feasible.  It provides a novel opportunity for effective postprandial control of glucose metabolism through the physiological route of the portal system. In addition, because it can be used in early diabetes, this approach holds the potential to protect beta cells and may thereby delay disease progression”, said Dr Narendra Chirmule, sr vice president & head of R&D, Biocon.

“We are grateful to BMS for their partnership in the early development of this unique program. The data is extremely promising and based on what we know today Tregopil may be positioned as a unique oral Insulin. Confirmation of these findings in the next phase of clinical studies will set the stage for a paradigm shift in the treatment of diabetes. This is an exciting moment for Biocon and hopefully for patients around the world. We have assembled a world renowned group of endocrinologists and diabetologists to work with us to drive the development of this molecule in the clinic,” said Kiran Mazumdar-Shaw, CMD, Biocon.

Dr Harold Lebovitz, diabetes expert and member,  Biocon’s Clinical Advisory Board, said that insulin Tregopil has the potential to provide the medical community with a physiological treatment for postprandial hyperglycemia. Orally administered, prior to meals, the drug is rapidly absorbed and reaches the liver within minutes through the portal vein. Insulin Tregopil absorption is over within 60 to 90 minutes. The two major complications of current insulin treatments, hypoglycemia and weight gain, could be potentially minimized by treatment with insulin Tregopil.

Prof Alan Cherrington, laboratory investigator, who has carried out the key pre-clinical research for IN-105 in dog models at Vanderbilt University, observed that it is becoming clear that a normal distribution of insulin between the liver and fat in a ratio of 3:1 is of therapeutic advantage and oral delivery of insulin represents one way to accomplish that.