Lexicon Pharmaceuticals, Inc., announced today that JDRF, the world's largest non-profit supporter of type 1 diabetes (T1D) research, will provide funding to support a Phase 2, randomized, double-masked, placebo-controlled clinical trial to evaluate the efficacy and safety of LX4211 in a younger population with T1D. Up to 76 individuals with T1D, younger than 30 years of age and with HbA1c levels greater than 9.0%, are expected to be randomly assigned to receive either placebo or a once daily 400mg dose of LX4211 and complete the 12-week treatment period. The primary objective of this study is to demonstrate the superiority of LX4211 versus placebo as adjunct to insulin treatment on HbA1c reduction at 12 weeks as well as several secondary endpoints, including reduced variability in blood glucose levels and lower insulin needs.
"JDRF has a strategic T1D research plan designed to deliver a sustained stream of new life-changing therapies, so we are pleased to collaborate with Lexicon on the development of LX4211 in T1D," said Sanjoy Dutta, Ph.D., JDRF's assistant vice president, translational development. "This collaboration is part of JDRF's Glucose Control Research Program whose goal is to develop and deliver improved insulin and non-insulin adjunct therapies that progressively improve glucose and overall metabolic control in individuals with T1D. We believe that LX4211's dual SGLT1/SGLT2 inhibitory mechanism offers an innovative and exciting opportunity to deliver on this goal and address an important unmet medical need in those with T1D struggling to achieve optimal glucose control target levels." "The results from our previous Phase 2 study of LX4211 in type 1 diabetes have encouraged us to also explore its potential application in this younger population for whom managing glucose variability is an especially difficult challenge and in which the significant majority are unable to achieve HbA1c targets," said Pablo Lapuerta, M.D., Lexicon's executive vice president and chief medical officer.
"Importantly, we hope to continue to see improvement in glycemic control with a longer treatment period combined with reductions in the amount of insulin required and related improvements in quality of life in this population of high unmet medical need. This study complements our ongoing preparations for Phase 3 in type 1 diabetes, which are proceeding, as well as our plans for LX4211 in type 2 diabetes." 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 a previous Phase 2 clinical trial of LX4211 in type 1 diabetes, LX4211 treatment was shown to reduce mean HbA1c by 0.55% compared to a reduction of only 0.06% with placebo (p=0.002) over a four-week treatment period. At the same time, LX4211 reduced the total daily mealtime bolus insulin dose by 32% compared to 6% for placebo (p=0.007), while reducing variability in blood glucose levels. These improvements were accompanied by significantly more time spent in the target glucose range of 70-180 mg/dl, a significant reduction in time in hyperglycemic range, and no increase in hypoglycemia.