Isis announces top-line results from ISIS-PTP1B Rx Phase 2 study in type 2 diabetes patients

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today top-line results from a Phase 2 study of ISIS-PTP1B_Rx in patients with type 2 diabetes. In the Phase 2 study patients treated with ISIS-PTP1B_Rx achieved statistically significant reductions in body weight and hemoglobin A1c (HbA1c). In patients treated with ISIS-PTP1B_Rx, a mean reduction in HbA1c of 0.7 percentage points from baseline was achieved at 36 weeks, compared to a mean reduction of 0.2 percentage points for placebo-treated patients (p=0.03). Patients treated with ISIS-PTP1B_Rx also experienced a mean reduction in body weight from baseline at 36 weeks (p=0.01). Isis plans to report the full data from this study at a medical meeting later this year.

"Despite currently available therapies, many patients with type 2 diabetes are still unable to control their blood glucose levels and eventually require the use of insulin therapy. The only class of insulin sensitizers currently available is limited in use due to side effects We designed ISIS-PTP1B_Rx to act as an insulin sensitizer to enhance glycemic control by specifically targeting protein-tyrosine phosphatase 1B (PTP-1B). The results from this study and our earlier clinical experience with PTP-1B suggest that addressing this novel therapeutic target for type 2 diabetes with ISIS-PTP1B_Rx may have the potential to offer a safer more effective approach for patients with type 2 diabetes who are progressing in their disease," said Sanjay Bhanot, M.D., Ph.D., vice president of clinical development and translational medicine at Isis Pharmaceuticals. "We are particularly encouraged that the improvements in glucose control and body weight continued to increase through the treatment period suggesting that longer-term treatment with ISIS-PTP1B_Rx could provide even greater glucose control."

"ISIS-PTP1B_Rx is a drug that has the potential to address several unique segments of the type 2 diabetes population and has the potential to both delay the need for insulin as well as to make insulin therapy more effective, thereby addressing a significant unmet medical need. We and our advisors believe that ISIS-PTP1B_Rx could be developed for patients with type 2 diabetes who are failing oral antidiabetic therapies or GLP-1 agonists, thereby delaying the need to initiate insulin therapy. These data also support the development of ISIS-PTP1B_Rx for patients who are insulin-resistant, remain uncontrolled even on high doses of insulin and in whom an insulin sensitizer could provide significant benefit. In addition, the combination of glucose control and weight loss demonstrated by ISIS-PTP1B_Rx in this study has the potential to be a significant advance in the treatment of obese patients with type 2 diabetes. We are in the process of discussing future development plans with potential partners in the diabetes space who could provide the expertise and resources necessary to enhance the value of this drug," said B. Lynne Parshall, chief operating officer at Isis Pharmaceuticals.

The Phase 2 study of ISIS-PTP-1B_Rx was a double-blinded, randomized, placebo-controlled study in 92 patients with type 2 diabetes who had uncontrolled blood sugar despite treatment with stable metformin with or without sulfonylurea therapy. Patients received 200 mg of ISIS-PTP1B_Rx or placebo for 26 weeks added to their stable doses of their background therapies. In this study, the average incoming HbA1c level was 8.6 percent and the average BMI was 34 kg/m². Patients in this study were not required to conform to any type of restrictive or weight-loss diet beyond the standard dietary restrictions they adhered to upon entry into the study. In this study, ISIS-PTP1B_Rx was generally well tolerated. The most common adverse event was infrequent injection site reactions, which were predominantly mild and resolved rapidly. There were no flu-like symptoms, no clinically significant abnormalities in laboratory parameters and no cases of severe hypoglycemia.