Emisphere Technologies, Inc. announced results from its 90-day, phase 2 study of its oral insulin product utilizing its eligen oral delivery technology. The four-arm study evaluated the safety and efficacy of low and high fixed doses of oral insulin tablets versus placebo in patients with Type 2 Diabetes Mellitus on existing oral metformin monotherapy.
The trial focused on the safety of oral insulin, specifically noting incidents of hypoglycaemia, as well as the occurrence of insulin antibodies. The efficacy component of the trial was designed to measure changes in Haemoglobin A1c (HbA1c) over 90 days, the standard for evaluating glucose control in Type II diabetics. An additional objective was to confirm that insulin delivered orally could be administered as a fixed dose product without the need to conduct glucose monitoring or titrate the insulin dose. The study met the company's objectives for both safety and efficacy.
The four arms of the study consisted of three doses of oral insulin (10mg QID, 5 mg QID and 10 mg BID) and placebo. There were 35 patients enrolled in each oral insulin arm of the trial, and 36 in placebo. Results showed that the total number of patients achieving a haemoglobin A1c (HbA1c) decrease of more than 1.1 per cent among the 35 patients dosed at the 10 mg QID dose of oral insulin was statistically significantly higher than in the 36 placebo patients. The study also demonstrated it was possible to deliver a fixed dose of insulin without the need to frequently monitor the patients' blood glucose or to titrate the dose for any reason. Blood glucose was measured on a monthly basis. A dose response was observed in Hba1c for the 10 mg QID and 5 mg QID doses of oral insulin versus placebo in patients enrolled with Hba1c values above 7.5 per ecnt and being treated with 1,500 mg per day or more of metformin; however, these values did not reach statistical significance.
Emisphere believes its oral insulin product had a very encouraging safety profile. During the study, there were no significant differences in number of hypoglycaemic events, serious adverse events, or insulin antibody formation for the orally administered insulin compared to placebo. There were no hypoglycaemic events in any of the high responder patients as measured by HbA1c. There were no insulin antibodies in any of the three oral insulin arms. The patients in all three active arms saw no change in weight and no nighttime hypoglycaemic events.
"We are very pleased with these study results. The goal of this study was to demonstrate that orally dosed insulin can be effective and safe in a real world setting over a protracted period of time, 90 days, without the need to titrate the dose or frequently monitor the blood glucose levels. Such a product can improve both the quality of care and the quality of life for many diabetics" said Michael M. Goldberg, MD, chairman and CEO of Emisphere Technologies. "The oral delivery of insulin has been an important goal of the pharmaceutical industry since insulin's discovery over 80 years ago. The results from this Phase 2 study represent a major milestone in Emisphere's efforts toward the accomplishment of that goal. The Phase 2 clinical trial was also designed to evaluate the safety and efficacy of various dosage strengths of our product compared to placebo. In- depth analysis of the data from this study should better define the patient populations most likely to benefit from the unique characteristics of oral insulin"
"This important achievement could not have been accomplished without the dedication and commitment of our staff and our expert collaborators from around the world. We were pleased with the quality and performance of our contract research organization, iGate, whose execution skills were excellent throughout the study. We look forward to extending our clinical database to further investigate the principal subpatient populations that would most benefit from the oral insulin product. We believe that these results will support our efforts to partner this program with a major pharmaceutical company. Finally while the phase 2 study was being conducted we tested several new oral insulin formulations in humans, which are more efficient in delivering insulin as compared to the formulation used in the phase 2." Dr. Goldberg concluded.
"We were very pleased to have had the opportunity to work on such an exciting and novel product. The investigators involved in the study consistently commented on the excellent safety and tolerability of the Emisphere oral insulin product. Significant interest was expressed by the investigators and their patients in an oral insulin product, which will not require dose titration or frequent glucose monitoring," said Vasu Ginde M.D., CEO of iGate Clinical Research International.
Emisphere's broad-based oral drug delivery technology platform, known as the eligen technology, is based on the use of proprietary, synthetic chemical compounds, known as Emisphere delivery agents, or "carriers". These molecules facilitate or enable the transport of the therapeutic macromolecules across biological membranes such as those of the gastrointestinal tract, and exert their desired pharmacological effect. Emisphere's eligen technology makes it possible to orally deliver a therapeutic molecule without altering its chemical form or biological integrity.