Inhale Therapeutic Systems Inc. reported Monday on Phase III studies conducted by Pfizer Inc., of New York. The data show that patients with Type II diabetes who had failed to meet recommended blood glucose levels with combination oral therapy achieved better glycemic control with Exubera inhaled insulin than patients who received only oral agents. The study also showed that Exubera inhaled insulin provided glycemic control equal to insulin injections in patients with Type I diabetes.
The data were presented at the 62nd annual scientific sessions of the American Diabetes Association in San Francisco that began Saturday and continues through today.
The three-month Phase III study involved 309 patients who had been diagnosed with Type II diabetes. The study examined whether Exubera, an inhaleable rapid-acting dry powder insulin, could provide better glycemic control when taken alone or in combination with oral agents, compared with patients taking only oral agents. Exubera was administered before meals.
Patients in the study taking either Exubera alone or Exubera plus oral agents experienced a significant decrease in hemoglobin (HbA1c). Patients taking oral agents alone experienced no change in HbA1c levels, which is a measurement of the average of a person's blood glucose levels over about 90 days. Patients taking Exubera also showed significantly greater decreases in both fasting plasma glucose concentrations and two-hour post-prandial glucose levels compared to patients taking only oral agents.
In other news from the sessions:
Aerogen Inc., of Mountain View, Calif., presented positive data from a second Phase II study indicating that Type II diabetic patients will be able to control their glucose levels with insulin as effectively with the Aerodose insulin inhaler as with subcutaneous injection. The data demonstrate that the Aerodose insulin inhaler provides efficient drug delivery, does not change the metabolic effect of insulin and provides a constant relative bioavailability, a finding the company said should facilitate an easy transfer of diabetic patients from injecting to inhaling insulin. The Aerodose insulin inhaler is a small, hand-held device.
Amylin Pharmaceuticals Inc., of San Diego, presented expanded analyses from two Phase II studies of AC2993 (synthetic exendin-4) in Type II diabetes. AC2993 is a 39-amino-acid peptide. The first study results demonstrated significant sustained reductions in post-meal glucose concentrations compared to placebo at 28 days. In addition, at day 28, 15 percent of patients on AC2993, compared to 4 percent of the placebo group, achieved HbA1c levels below 7 percent. The second trial was a dose-ranging study of patients with Type II diabetes who were inadequately controlled using metformin or diet alone. The study examined the day-long effects of sustained circulating concentrations of AC2993, which demonstrated clinically significant reductions in pre-meal, post-meal and fasting plasma glucose concentrations at all doses studied compared to placebo.
BioStratum Inc., of Research Triangle Park, N.C., said that Pyridorin (pyridoxamine) was the focus of three presentations. Pyridorin is a small molecule that inhibits formation of harmful advanced glycation end-products and is in Phase II trials. In an animal model of Type II diabetes, the albumin/creatinine ratio, a marker of kidney damage, in urine was significantly decreased in the Pyridorin group at the study's end compared to the untreated group. The study also showed that the drug reduced microscopic lesions in the kidney when compared to untreated animals at the end of the study. In an animal study of Type I diabetes, Pyridorin treatment inhibited the development of acellular capillaries in the retina, an early marker of diabetic retinopathy.
Emisphere Technologies Inc., of Tarrytown, N.Y., presented proof-of-concept clinical results showing that an oral formulation of insulin resulted in clinically significant absorption from the gastrointestinal tract, with large systemic concentrations. The company said the data confirmed Emisphere's oral drug delivery technology is effective because insulin, when given orally, cannot be absorbed into the bloodstream due in part to the relatively large size of the molecule. The study, conducted at Medeval Ltd. in Manchester, UK, included 20 healthy volunteers.
Entelos Inc., of Menlo Park, Calif., and the American Diabetes Association said Johnson & Johnson Pharmaceutical Research & Development LLC, of La Jolla, Calif., will be the first company to participate in the Diabetes Research Forum. The forum is a scientific collaboration to advance research for the prevention, treatment and cure of Type II diabetes. The research conducted by the forum will be provided to certain pharmaceutical and biotechnology companies. Entelos creates computer models that simulate human disease and predict patient responses to treatment.
Generex Biotechnology Corp., of Toronto, said studies it presented indicate that the company's Oralin oral insulin formulation has the potential to be used safely and effectively in place of injected insulin to treat Type I and Type II diabetes. The study found that the pharmacokinetics of oral spray insulin were similar to lispro insulin, reaching peak plasma insulin levels 30 minutes after administration and lowest levels at 240 minutes. As expected, regular insulin reached peak and steady-state levels between 30 and 120 minutes. Oralin is delivered as a fine spray to the buccal cavity via Generex's Rapidmist device. A second study showed that oral insulin spray taken at meal times was associated with a significantly lower post-prandial glucose rise (9 percent vs. 27 percent) when compared with days in which patients received oral agents alone.
Incara Pharmaceuticals Corp., of Research Triangle Park, N.C., said its catalytic antioxidant delayed the onset of Type I diabetes in a mouse model, an observation recently published in the journal Diabetes. The findings demonstrated that AEOL 10113 reduced the extent of T-lymphocyte proliferation and release of inflammatory mediators in response to a specific antigen. Such increases occur in the autoimmune response to pancreatic beta cell antigens and are associated with the death of those cells, which leads to Type I diabetes.
Insmed Inc., of Richmond, Va., presented data from a Phase II trial showing the company's orally active insulin sensitizer, INS-1, improved lipid profiles in patients with Type II diabetes and synergistically improved lipid profiles in those patients receiving statin therapy. In a Phase II trial in patients receiving sulfonylurea therapy, an analysis of lipid profiles revealed patients receiving INS-1 with statin therapy experienced even greater improvements in total cholesterol and LDL cholesterol, as well as improvements in apolipoprotein-B, compared to patients receiving INS-1 but no statin treatment.
Nobex Corp., of Research Triangle Park, N.C., reported new clinical and preclinical data in five separate abstracts on its investigational oral insulin product, which is being developed through a strategic alliance with GlaxoSmithKline, of Research Triangle Park, N.C. Among other results, a controlled 31-patient trial suggested that, in Type I diabetic patients, Nobex oral insulin may provide post-meal glucose control similar to that achieved with insulin lispro.