Isis heralds positive PhII diabetes results for a leading antisense drug

Isis ($ISIS) says its lead diabetes drug scored a success in a Phase II study, with both doses of ISIS-GCGR spurring a significant drop in blood glucose levels after 13 weeks of therapy in a group of treatment-resistant patients. And the antisense therapy hit its marks on HbA1c without spurring some of the troubling side effects that may hinder rival therapies in the pipeline.

GCGR works by targeting the glucagon receptor, looking to dial down the effect of a hormone that triggers glucose production in Type 2 diabetics. This was a small study, with only 75 patients, but it does set the stage for much larger studies that will be needed to test this antisense tech for a disease that afflicts a huge patient population.

Investigators said that the drug reduced blood glucose levels by 2 percentage points in the 200 mg arm and 1 percentage point  for the 100 mg group. There was no comparative placebo data. Details will follow at an upcoming scientific session.

"Unlike results with previous small molecule inhibitors of glucagon receptor, patients treated with ISIS-GCGRRx did not experience significant changes in LDL-C, blood pressure or body weight gain," says Sanjay Bhanot, vice president of clinical development and translational medicine at Isis. "Additionally, we do not expect ISIS-GCGRRx to produce drug-drug interactions, which means ISIS-GCGRRx has the potential to be used in combination with currently available therapies.  ISIS-GCGRRx is a dual acting drug designed to effectively balance reduction of hepatic glucose production and GLP-1 increases.  The increases in GLP-1 observed in this study are consistent with our preclinical and Phase 1 experience with ISIS-GCGRRx and support the dual action of ISIS-GCGRRx. Given the remarkable results we have observed in this 13 week study, we plan to optimize dose and dosing schedules for our longer-term studies of ISIS-GCGRRx in patients with type 2 diabetes."

The side effect profile can be just as important as efficacy in diabetes drug development. Earlier this week Eli Lilly ($LLY) reported that its basal insulin peglispro, a potential rival to the bestselling Lantus, spurred a statistically significant increase in triglycerides--a type of blood fat. Also, more patients taking BIL had an increase in the liver enzyme ALT, though there were no reports of severe liver damage. The drug worked in reducing HbA1c, but some analysts fretted about the potential safety issues.

- here's the release