Type 2 Diabetes
Dutogliptin for the Treatment of Type 2 Diabetes
We are developing dutogliptin tartrate (PHX1149) for the treatment of Type 2 diabetes, a chronic disease associated with abnormally high levels of glucose in the blood. Type 2 diabetes affects more than 160 million people worldwide, including approximately 18 million people in the United States. According to the American Diabetes Association, direct and indirect expenditures related to diabetes comprise 11% of all U.S. healthcare expenditures. In 2007, worldwide sales of diabetes medications totaled over $21 billion, with approximately $14 billion spent on oral anti-diabetic medications, or OADs.
Despite existing therapies and increasing awareness of the need for careful glucose control, nearly two-thirds of patients diagnosed with Type 2 diabetes do not achieve and maintain proper control of blood glucose. Furthermore, many existing therapies result in common side effects, including an increased risk of hypoglycemia, or abnormally low blood glucose levels, weight gain and gastrointestinal problems, as well as less common adverse events such as heart attacks and congestive heart failure. As a result, we believe there is a need for improved therapies for Type 2 diabetes.
DPP-4 inhibitors represent the most recently approved class of agents for the treatment of Type 2 diabetes. DPP-4 inhibitors prevent the enzyme DPP-4 from breaking down GLP-1, thereby increasing the levels of this hormone in the digestive tract and the blood. The increased levels of intact GLP-1 stimulate insulin production by the pancreatic beta cells and reduce glucagon production by the pancreas, both of which result in reduced blood glucose levels. In clinical trials to date, DPP-4 inhibitors have been well tolerated and have provided clinically meaningful reductions in HbA1c when used as the sole medical treatment, as well as important incremental decreases in HbA1c when used in combinations with other anti-diabetic medications. DPP-4 inhibitors also offer several advantages over other types of diabetes therapies, including: absence of weight gain and edema, low risk of hypoglycemia, and potential for improved beta cell function.
Our lead product candidate, dutogliptin tartrate, is a dipeptidyl peptidase-4, or DPP-4, inhibitor that we are developing as a once daily, oral treatment for Type 2 diabetes. DPP-4 inhibitors represent a new class of OADs that improve the control of blood glucose and have a favorable tolerability profile.
Our Phase 2a clinical trial of dutogliptin in patients with Type 2 diabetes demonstrated that dutogliptin was well tolerated and met its primary endpoint of reducing post-meal blood glucose levels. In 12-week clinical trials of other DPP-4 inhibitors, postprandial glucose levels have been shown to be correlated with reductions in hemoglobin A1c, or HbA1c, a measure of blood glucose control. The FDA currently approves diabetes medications based primarily on safety and on effectiveness in lowering HbA1c levels.
In our randomized, 422 patient Phase 2b clinical trial completed in the first quarter of 2008, dutogliptin demonstrated statistically significant reductions in HbA1c when administered in combination with existing drugs for the treatment of Type 2 diabetes. Dutogliptin also demonstrated statistically significant effects on secondary efficacy endpoints, including change in fasting blood glucose levels, change in postprandial blood glucose levels and achievement of a target HbA1c level of less than 7%. In addition, the safety and tolerability of dutogliptin were not substantially different from placebo in this Phase 2b clinical trial or in our earlier Phase 2a and Phase 1 clinical trials.
At an end-of-Phase 2 meeting, the FDA agreed that we could proceed with our planned Phase 3 clinical trials and confirmed the scope of the trials necessary to support a marketing application for dutogliptin. We expect to commence our Phase 3 clinical program in the latter half of 2008.
We believe DPP-4 inhibitors will be differentiated in the market primarily based on their tolerability and convenience. Based on the results of our preclinical studies and clinical trials, we believe dutogliptin has the potential to compete with sitagliptin and other DPP-4 inhibitors in development for the treatment of Type 2 diabetes.