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Diabetes Drug ISIS-GCGRRx Shows Promise in Mid-Stage Trial

HbA1c reduced by more than 2% after 13 weeks of dosing

Positive data have been reported from a phase II study of ISIS-GCGRRx (Isis Pharmaceuticals), a small-molecule glucagon receptor inhibitor, in patients with type-2 diabetes uncontrolled on stable metformin therapy.

In this study, patients in the efficacy population treated with ISIS-GCGRRx achieved statistically significant reductions in measures of glucose control. The absolute mean reductions in hemoglobin A1c (HbA1c) were greater than 2 percentage points (P = 0.001) and greater than 1 percentage point (P = 0.001) in the 200-mg and 100-mg cohorts, respectively, compared with baseline after 13 weeks of treatment.

Patients treated with ISIS-GCGRRx also experienced increased plasma levels of glucagon-like peptide-1 (GLP-1).

Additional details from this study will be presented at the American Diabetes Association 74th Scientific Sessions, to be held June 13–17 in San Francisco, California.

This double-blind, randomized, placebo-controlled study involved 75 patients with type-2 diabetes who had uncontrolled blood sugar despite treatment with stable metformin therapy. The patients received either 100 mg or 200 mg of ISIS-GCGRRx or placebo for 13 weeks, added to their stable doses of metformin. The average incoming HbA1c level was 8.7%.

After only 13 weeks of dosing, sustained, dose-dependent, statistically significant mean reductions in HbA1c were achieved in patients treated at both doses of ISIS-GCGRRx. Additional measures of glucose control, including serum fructosamine and fasting plasma glucose levels, were also significantly reduced in patients treated with ISIS-GCGRRx. The observed improvement in glucose control was in addition to those achieved with each patient’s existing therapeutic regimen of metformin.

ISIS-GCGRRx was generally well tolerated. The most common adverse events were injection-site reactions, which were predominantly mild and typically resolved rapidly. There were no flu-like symptoms, no abnormalities in renal function, no clinically meaningful changes in other laboratory values, and no cases of symptomatic hypoglycemia.

As has been observed with small-molecule inhibitors of the glucagon receptor, liver enzyme elevations that were not associated with elevated bilirubin or other indicators of liver damage were observed. These liver enzyme elevations are consistent with the pharmacology of glucagon receptor inhibition. ISIS-GCGRRx was not associated with increases in low-density lipoprotein cholesterol, blood pressure, or body weight (side effects associated with some small-molecule inhibitors of the glucagon receptor).

ISIS-GCGRRx is being developed for patients with advanced diabetes whose glucose is uncontrolled with current therapies.

Source: Isis Pharmaceuticals; May 14, 2014.

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