Lower HbA1c and body weight with investigational diabetes drug
Phase 2 results of a study investigating the investigational ISIS-PTP1BRx in patients with type 2 diabetes show that patients receiving ISIS-PTP1BRx achieved reductions in body weight and HbA1c.
ISIS-PTP1BRx has been designed to act as an insulin sensitizer to enhance glycaemic control by specifically targeting protein-tyrosine phosphatase 1B (PTP-1B).
In patients treated with ISIS-PTP1BRx, a mean reduction in HbA1c of 0.7 percentage points from baseline was achieved at 36 weeks (study designed as 26 weeks of treatment), compared to a mean reduction of 0.2 percentage points for placebo-treated patients (p=0.03). Patients treated with ISIS-PTP1BRx also experienced a mean reduction in body weight from baseline at 36 weeks (p=0.01).
The Phase 2 study of ISIS-PTP1BRx 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-PTP1BRx 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-PTP1BRx 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.
“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-PTP1BRx 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 in a press release. "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-PTP1BRx could provide even greater glucose control."
ISIS-PTP1BRx has the potential to both delay the need for insulin as well as to make insulin therapy more effective. The company and its advisors “believe that ISIS-PTP1BRx 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-PTP1BRx for patients who are insulin-resistant, remain uncontrolled even on high doses of insulin and in whom an insulin sensitizer could provide significant benefit.”
The full data from this study will be presented at a medical meeting later this year.