Lexicon Pharmaceuticals, Inc., a biopharmaceutical company focused on developing breakthrough treatments for human disease, announced positive, top-line results in a phase 2 clinical trial of LX4211 in type 1 diabetes, which achieved the primary endpoint of reducing mealtime insulin use as well as several secondary endpoints, including improved glycemic control.  LX4211 is an oral, first-in-class, dual inhibitor of sodium glucose transporters 1 and 2 (SGLT1 and SGLT2) that is designed to lower blood glucose levels through two insulin-independent mechanisms of action.

In the placebo-controlled, double-blind, 28-day study, LX4211 reduced the total daily mealtime bolus insulin dose by 32% compared to 6% for placebo (p=0.007), while significantly improving glycemic control with a mean HbA1c reduction of 0.55% in the LX4211-treated group compared to a reduction of only 0.06% with placebo (p=0.002).  This improvement was accompanied by significant improvement in the time spent in a glucose range of 70-180 mg/dl, a significant reduction in time in hyperglycemic range, and no increase in hypoglycemia.  Multiple measures indicated that LX4211 treatment resulted in reduced variability in blood glucose levels.  Overall, LX4211 was well tolerated with no discontinuations of study medication due to adverse events.

“The results from this study provide a clear demonstration of proof-of-concept of LX4211 as an oral, investigational new drug for type 1 diabetes complementing insulin therapy,” said Arthur Sands, Lexicon’s president and chief executive officer.  “The magnitude of improved glycemic control by several measures, including HbA1c in only four weeks, and lower insulin requirements are highly encouraging and support the progression of LX4211 into late-stage development for type 1 diabetes.”

In this multicenter study, 33 patients with poorly controlled type 1 diabetes on either an insulin pump or multiple insulin injection therapy were randomized 1:1 to receive either placebo or a 400 mg dose of LX4211 orally once per day before breakfast for four weeks. Patients adjusted their insulin as needed, recorded their blood sugars, and then were evaluated at the end of the study for amount of insulin used and glycemic control, as measured by HbA1c, continuous glucose monitors and serum blood glucose measures. Lexicon plans to present full results of the study at a scientific congress.

“An oral agent benefiting patients with type 1 diabetes through both substantial improvements in glucose control and significant reduction in the use of insulin with no increase in hypoglycemia is both new and clinically meaningful,” said Pablo Lapuerta, Lexicon’s chief medical officer.  “These results provide a strong rationale for demonstrating the effectiveness of LX4211 as an adjunct to insulin in Type 1 diabetes in a longer-term phase 3 programme.”

Type 1 diabetes is a serious condition affecting more than one million people in the United States, both children and adults. Type 1 diabetes is an autoimmune disease in which a person’s pancreas stops producing insulin, a hormone that enables people to get energy from food. It occurs when the body’s immune system attacks and destroys the insulin-producing cells in the pancreas. Insulin is a required treatment, with few additional treatment options.  The effectiveness of insulin is limited by concerns about potentially serious hypoglycemia; therefore, most patients with type 1 diabetes do not achieve their targets for glucose control. In addition, insulin therapy does not necessarily prevent the possibility of the disease’s serious complications, which may include kidney failure, blindness, nerve damage, heart attack and stroke. As an oral agent, LX4211 is designed to delay the absorption of glucose in the gastrointestinal tract and enhance glucose excretion in the kidney, allowing glucose control to improve and insulin doses to be reduced.