Isis Initiates Phase 1 Study of ISIS-PTP1BRx to Treat Type 2 Diabetes
- Category: DNA RNA and Cells
- Published on Thursday, 21 July 2011 03:00
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Isis Pharmaceuticals announced 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
CARLSBAD, CA, USA | July 21, 2011 | Isis Pharmaceuticals, Inc. (NASDAQ:ISIS - News) 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.
ISIS-PTP1BRx is an antisense drug that targets PTP-1B, a phosphatase that negatively regulates insulin receptor signaling and is responsible for turning off the activated insulin receptor. Reducing PTP-1B enhances insulin activity. Scientists have long recognized PTP-1B as an attractive target to treat diabetes, but due to structural similarities among closely related proteins, pharmaceutical companies have had difficulty identifying small molecule drugs with sufficient specificity to be safe. ISIS-PTP1BRx selectively inhibits the production of PTP-1B without affecting other closely related proteins that, when inhibited, could lead to unwanted side effects. ISIS-PTP1BRx may offer new treatment to patients who do not respond adequately to currently available therapies such as glitazones, sulfonylureas, metformin, and GLP-1 based therapies, and has the potential to be used in combination with such other therapies.
ABOUT ISIS PHARMACEUTICALS, INC.
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 24 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic and severe and rare/neurodegenerative diseases, and cancer. Isis' partner, Genzyme, a sanofi company, plans to commercialize Isis' lead product, mipomersen, in 2012. Isis' patents provide strong and extensive protection for its drugs and technology. Additional information about Isis is available at www.isispharm.com.
SOURCE: ISIS PHARMACEUTICALS