Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today that it has initiated a Phase 1 clinical study for ISIS-PTP1BRx, an antisense drug for the treatment of type 2 diabetes targeting protein tyrosine phosphatase-1B, PTP-1B. ISIS-PTP1BRx is designed to increase the body's sensitivity to the natural hormone insulin, resulting in better glucose control for patients with type 2 diabetes. Because of its unique mechanism ISIS-PTP1BRx has the potential to contribute to the treatment of type 2 diabetes without causing weight gain or hypoglycemia. The reductions in LDL-C produced by PTP-1B inhibition should also provide an added benefit to patients.
"We are developing ISIS-PTP1BRx for patients whose glucose is inadequately controlled by insulin or oral therapies. Having demonstrated the attractive profile of a PTP-1B inhibitor with ISIS 113715, we are now proceeding with the development of a more potent PTP-1B inhibitor," said Sanjay Bhanot, M.D., Ph.D., Vice President of Metabolic Disorders and Translational Medicine at Isis. "We believe that ISIS-PTP1BRx could be a safer insulin sensitizer. The only class of insulin sensitizers currently available also broadly affects the transcription of multiple genes, which leads to side effects. Some of these side effects, such as increases in LDL-C, weight gain, and thinning of bones are particularly problematic in diabetics. Because ISIS-PTP1BRx selectively reduces only the PTP-1B protein, a mechanism distinct from current insulin sensitizers, it is unlikely to have those side effects."
Earlier Phase 2 studies of ISIS 113715 provided evidence of the therapeutic potential of inhibiting PTP-1B. In those studies, PTP-1B inhibition improved glucose control and reduced LDL-C in both newly diagnosed diabetic patients and in patients who were taking sulfonylureas. Those studies also showed that PTP-1B inhibition did not cause weight gain, another substantial advantage in the treatment of diabetic patients who are frequently obese and at high cardiovascular risk. The data from these studies support the development of ISIS-PTP1BRx and should allow a very rapid route to clinical proof-of-concept.
ISIS-PTP1BRx has the potential to be broadly useful in combination with most of the other commonly used drugs to treat patients with diabetes, including insulin, GLP-1 agonists, and more traditional drugs like metformin. The initial clinical development plan for ISIS-PTP1BRx will focus on treating diabetic patients who are inadequately controlled on insulin, helping them utilize insulin more efficiently; and patients who are beginning to fail oral therapies, extending the time they have before becoming dependent on insulin.
Global gap in diabetes prevalence and treatment has widened since 1990