Lexicon Phase II type 1 diabetes trial meets primary and secondary endpoints

US-based biopharmaceutical firm Lexicon Pharmaceuticals has reported positive, top-line results from a Phase II clinical trial of LX4211, an oral, first-in-class, dual inhibitor of sodium glucose transporters 1 and 2 (SGLT1 and SGLT2), for treatment of patients with type 1 diabetes.

The company said that the trial achieved the primary endpoint of reducing mealtime insulin use and also several secondary endpoints, including improved glycaemic control.

LX4211 is designed to lower blood glucose levels through two insulin-independent mechanisms of action.

In the 28-day, placebo-controlled, double-blind trial, LX4211 reduced the total daily mealtime bolus insulin dose by 32% compared with 6% for placebo, while improving glycaemic control with a mean HbA1c reduction of 0.55% in the LX4211-treated group compared to a reduction of only 0.06% with placebo.

According to the company, the improvement was accompanied by improvement in the time spent in a glucose range of 70mg-180mg/dl, a significant reduction in time in hyperglycaemic range, and no increase in hypoglycaemia.

Several measures showed that treatment with LX4211 resulted in reduced variability in blood glucose levels.

On the whole, LX4211 was well-tolerated with no discontinuations of trial medication due to adverse events.

Lexicon president and chief executive officer Arthur Sands said the results from the trial provide a clear demonstration of proof-of-concept of LX4211 as an oral, investigational new drug for type 1 diabetes complementing insulin therapy.

"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," Sands said.

In the trial, 33 patients with poorly controlled type 1 diabetes on either an insulin pump or multiple insulin injection therapy were randomised 1:1 to receive either placebo or a 400mg dose of LX4211 orally once per day before breakfast for four weeks.

Lexicon chief medical officer Pablo Lapuerta said 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.

"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," Lapuerta said.

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Image: Type 1 diabetes is an autoimmune disease in which a person’s pancreas stops producing insulin. Photo: courtesy of Ras67.