Jun 7 2004
Research presented today showed that the investigational drug, LAF237, the first in a new class, improved glycemic control in patients with type 2 diabetes. In this study, LAF237, which is administered as a tablet to be taken orally, was added to the standard diabetes treatment metformin in patients whose diabetes was not adequately controlled by metformin alone.
Presented at the annual scientific meeting of the American Diabetes Association, the study demonstrated that the glucose reductions from the combined therapy were sustained for one year with LAF237. "These phase II findings underscore the exciting promise of LAF237 and the role of DPP-4 inhibition," said Malcolm MacNab, M.D., vice president, Cardiovascular and Metabolism. "It opens a whole new way to look at controlling type 2 diabetes at a time when the disease is reaching worldwide epidemic proportions. We are pleased that phase III trials have been initiated to further explore the potential of this novel and orally administered compound." Exploring new diabetes treatments like LAF237 is critically important, especially given that the World Health Organization projects the number of people with diabetes will double to 366 million by 2030. Last year alone, more than 3.2 million deaths were attributed to diabetes or diabetes-related causes.
Novartis is leading the way in the development of this new class of oral anti-diabetes agents called DPP-4 inhibitors. Researchers studying LAF237 hope to show that the therapy will help address the underlying imbalance between insulin and glucose production that is the cause of type 2 diabetes. LAF237 works by increasing the levels of a specialized incretin hormone called GLP-1 by blocking the action of DPP-4, an enzyme that normally inactivates GLP-1. GLP-1 is secreted from the intestine in response to food, and it stimulates insulin production by the beta cells of the pancreas. GLP-1 also reduces the secretion of glucagon, another hormone that signals the liver to produce glucose.
Based on the strength of these data and other findings from phase II studies, Novartis launched a full phase III clinical trial program earlier this year. The completed phase II trial presented today was designed to assess the safety and dosing of LAF237 and to make initial efficacy evaluations. "In this study HbA1c levels, the primary long-term measure of glycemic control, decreased significantly when LAF237 was added to a patient's course of therapy, and this benefit was maintained for one year," said Richard Pratley, M.D., Professor of Medicine, University of Vermont College of Medicine. "Bringing patients to an ideal HbA1c level early in the disease process and maintaining those levels for as long as possible is critical to the management of type 2 diabetes, making these findings very encouraging." Patients who were part of the metformin plus LAF237 treatment arm sustained an HbA1c level that was on average 1.1 percent lower than the group on metformin plus placebo. Glucose levels measured after 8-12 hours of fasting and those measured 1-2 hours after eating a meal were also reduced in patients taking metformin plus LAF237 versus continued therapy with metformin alone. In addition, the metformin plus LAF237 group maintained lower HbA1c levels for one year.
In contrast, researchers saw an increase in HbA1c in the metformin only group during the same period. LAF237 was found to be well tolerated with 76.2 and 89.7 percent of patients completing the 52-week investigation in the LAF237 plus metformin arm and metformin plus placebo arms respectively. The metformin plus LAF237 group reported a slightly higher percent of patients with at least one adverse event (69 percent) compared to the metformin plus placebo group (58.6 percent), however, suspected drug-related adverse events were 4.8 percent and 6.9 percent respectively. Four patients in the metformin plus LAF237 group discontinued due to an adverse event.
Three patients reported hypoglycemic events in the metformin plus LAF237 group, none of which was considered serious. No patient discontinued study participation due to hypoglycemia (low blood sugar). Also being presented this week at the ADA meeting are two additional studies from the LAF237 clinical development program; a 12-week monotherapy trial and a pharmacokinetic/pharamcodynamic interaction study with glyburide. Diabetes affects about 170 million people worldwide, afflicting increasing numbers of people in both first and developing world countries.
According to the U.S. Centers for Disease Control (CDC), more than 18 million Americans have diabetes, making it the sixth leading cause of death in the United States and a major contributor to heart disease, stroke, blindness, kidney disease, and non-traumatic leg and foot amputations.