"These results reported today represent the potential for a major advance in diabetes therapeutics. ISIS-GCGRRx employs a unique mechanism to treat patients with type 2 diabetes. It is well known that as type 2 diabetes progresses, dysregulated glucagon action becomes a more significant contributor to the disease. The ability of ISIS-GCGRRx to improve glycemic control without causing any clinically significant increases in blood pressure or lipids offers a significant advantage for both patients and treating physicians," said
"Glucagon is a hormone that opposes the action of insulin and causes increased glucose production from the liver. In patients with advanced diabetes, uncontrolled glucagon action can lead to a significant increase in blood glucose levels. Therefore, attenuating glucagon action should have a significant glucose lowering effect in patients with severe diabetes," said
This Phase 2 study of ISIS-GCGRRx was a double-blinded, randomized, placebo-controlled study in 75 patients with type 2 diabetes who had uncontrolled blood sugar despite treatment with stable metformin therapy. Patients received either 100 mg or 200 mg of ISIS-GCGRRx or placebo for 13 weeks added to their stable doses of metformin. In this study, the average incoming HbA1c level was 8.7 percent. After only 13 weeks of dosing, robust and sustained, dose-dependent, statistically significant mean reductions in HbA1c were achieved in patients treated at both doses. 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 in the study. The most common adverse event was infrequent 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 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 LDL-C, blood pressure or body weight gain (side effects associated with some small molecule inhibitors of glucagon receptor).
ISIS-GCGRRx is a part of Isis' metabolic franchise that also includes ISIS-PTP1BRx and ISIS-GCCRRx. Each of these drugs is designed to act through a distinct mechanism to improve insulin sensitivity and/or reduce glucose production in patients with type 2 diabetes. Isis is developing ISIS-GCGRRx for patients with advanced diabetes whose glucose is uncontrolled with current therapies.
Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners. Isis' broad pipeline consists of 32 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic, severe and rare diseases, including neurological disorders, and cancer. Isis' partner, Genzyme, is commercializing Isis' lead product, KYNAMRO®, in
This press release includes forward-looking statements regarding the development, activity, therapeutic potential and safety of ISIS-GCGRRx in treating patients with type 2 diabetes. Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Isis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Isis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis' programs are described in additional detail in Isis' annual report on Form 10-K for the year ended
In this press release, unless the context requires otherwise, "Isis," "Company," "we," "our," and "us" refers to
D. Wade Walke, Ph.D., Vice President, Corporate Communications and Investor Relations, 760-603-2741 or Amy Blackley, Ph.D., Associate Director, Corporate Communications, 760-603-2772