Lexicon Pharmaceuticals Reports Additional Positive Data From Pivotal InTandem1 Phase 3 Study For Sotagliflozin In Patients With Type 1 Diabetes

THE WOODLANDS, Texas, May 11, 2017 /PRNewswire/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced today additional positive data from the Phase 3 inTandem1 study. It was previously announced that both doses of sotagliflozin achieved the primary endpoint of the inTandem1 study, showing statistically significant reductions in A1C at 24 weeks in patients with type 1 diabetes on a background of optimized insulin. New key findings include meaningful benefit of sotagliflozin on body weight in patients with type 1 diabetes and on systolic blood pressure in hypertensive patients with type 1 diabetes. In addition, the Company announced achievement of important secondary endpoints including net benefit, bolus insulin use, fasting plasma glucose and patient reported outcomes.

In a key secondary endpoint, patients taking sotagliflozin experienced a mean reduction from baseline in body weight after 24 weeks of treatment of 1.6 kg for the 200mg dose and 2.7 kg for the 400mg dose, compared to a mean body weight gain of 0.8 kg for patients on placebo (p<0.001 for both doses). Sustained effects on body weight were also seen at 52 weeks.

In addition, systolic blood pressure (SBP) in the subset of type 1 diabetic patients in the study with baseline hypertension (SBP ≥130 mmHg) was reduced by 9.9 mmHg and 11.0 mmHg at week 12 when treated with 200 mg and 400 mg of sotagliflozin, respectively, compared to a reduction of 4.4 mmHg on placebo (p=0.017 and p=0.003 for the 200 mg and 400 mg doses, respectively).

Notably, the outcome on every secondary endpoint favored sotagliflozin over placebo, with results for the 400 mg dose having achieved statistical significance for all six secondary endpoints (results for the first two secondary endpoints were also statistically significant for the 200 mg dose):

• the proportion of patients achieving A1C <7.0% with no episode of severe hypoglycemia or diabetic ketoacidosis ("net benefit");
• body weight;
• bolus insulin use;
• fasting plasma glucose;
• Diabetes Treatment Satisfaction Questionnaire status (DTSQs) score; and
• 2-item Diabetes Distress Screening Scale (DDS2) questionnaire score.

Sotagliflozin was generally well tolerated during the 28-week extension period, with rates of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and discontinuations due to AEs that were consistent with rates seen in the initial 24-week treatment period. The rate of severe hypoglycemia was the same or lower for the sotagliflozin arms than placebo during the 28-week extension period (10 patients (4.3%) for placebo, compared to 10 (4.2%) and 6 (2.5%) for sotagliflozin 200 mg and 400 mg, respectively), and was slightly lower overall than the rate seen in the initial 24-week treatment period. The rate of diabetic ketoacidosis (DKA) during the 28-week extension period was slightly higher than the rate seen in the initial 24-week treatment period for placebo (one patient, 0.4%) and the 200 mg dose arm (6, 2.5%) and lower for the 400 mg dose arm (3, 1.3%).  

"Sotagliflozin's ability to improve both A1C and other measures of health such as body weight and blood pressure holds promise for addressing important areas of need in type 1 diabetes, and the additional inTandem1 results announced today highlight the differentiated profile of sotagliflozin in the type 1 diabetes landscape," said Lonnel Coats, Lexicon's president and chief executive officer. "In the coming weeks, we look forward to the outcome of inTandem3, with its 'net benefit' primary efficacy endpoint that measures the proportion of patients achieving an A1C of less than 7% without a severe hypoglycemia or DKA event. We saw favorable results on the same endpoint in inTandem1 and inTandem2 and remain confident about replicating these data in inTandem3."

"Type 1 diabetes is a tough disease for patients and their providers to take care of. The potential of sotagliflozin to lower blood glucose and favorably affect body weight and blood pressure is tremendous," said John Buse, M.D., Ph.D., lead investigator of inTandem1 and Professor of Medicine, Chief of the Division of Endocrinology and Metabolism, Director of the Diabetes Care Center, and Executive Associate Dean for Clinical Research at the University of North Carolina School of Medicine. "If approved, sotagliflozin could be an important oral therapy for individuals with type 1 diabetes while on insulin."

About inTandem1

The Phase 3 study known as inTandem1 was a double-blind, placebo-controlled, multi-center study of 793 patients in the U.S. and Canada with type 1 diabetes on insulin pump or multiple daily injection therapy who had an A1C level entering the study between 7.0% and 11.0%. The three-arm study evaluated two doses of sotagliflozin, 200mg and 400mg, each taken once daily before the first meal of the day, against placebo. Prior to randomization, insulin was optimized for all patients over a six-week period, with the objective of improving glycemic control using insulin alone. After completion of this optimization period, patients were maintained on optimized insulin and randomized to one of two doses of sotagliflozin or placebo, and their baseline, post-optimization A1C was measured. The mean baseline A1C level at the time of randomization after the six-week optimization period was 7.6% for all three dose arms.

The primary endpoint of the study was change in A1C from baseline after a 24-week period of treatment. The trial had a double-blind long-term extension of 28 weeks, with a total treatment duration of 52 weeks. There were 268 patients in the placebo arm, 263 patients in the 200mg dose arm, and 262 patients in the 400 mg dose arm. The overall mean placebo adjusted A1C reduction was 0.35% in the 200 mg dose arm (p<0.001) and 0.41% in the 400mg dose arm (p<0.001) over the initial 24-week treatment period. The A1C benefit achieved with sotagliflozin was sustained over the full 52-week duration of the study for both the 200 mg and 400 mg doses (p<0.001 at week 52).

Sotagliflozin was generally well tolerated during the study. Across all three dose arms (placebo, 200mg, 400mg), over the full 52 weeks of treatment, the incidences of AEs were 80.6%, 81.7% and 79.8%, respectively; the incidences of SAEs were 7.5%, 10.3% and 11.1%, respectively; and discontinuations due to AEs were 4.1%, 4.9% and 6.5%, respectively. There was one death in the study in the placebo arm and no deaths in either sotagliflozin arm. 

Two primary safety concerns for patients with type 1 diabetes are severe hypoglycemia and DKA. The number of patients with severe hypoglycemia events during the full 52 weeks of treatment was 26 (9.7%), 17 (6.5%), and 17 (6.5%) in the placebo, 200 mg and 400 mg dose arms, respectively. The number of patients with DKA events during the full 52 weeks of treatment was 1 (0.4%), 9 (3.4%), and 11 (4.2%) in the placebo, 200 mg and 400 mg dose arms, respectively. 

Lexicon is conducting another, similar pivotal Phase 3 clinical trial predominantly in Europe (inTandem2), from which top-line, primary efficacy endpoint and safety data at 24 weeks has previously been reported and additional data from secondary endpoints as well as pooled continuous glucose monitoring (CGM) results from inTandem1 and inTandem2 are expected in the third quarter of 2017. Lexicon is conducting a third, global Phase 3 clinical trial, inTandem3, studying approximately 1,400 type 1 diabetes patients treated with sotagliflozin 400mg once daily or placebo on a background of any insulin therapy, but without insulin optimization prior to randomization. Top-line data from inTandem3 is expected in the coming weeks.

About Sotagliflozin

Discovered using Lexicon's unique approach to gene science, sotagliflozin is a first-in-class, oral dual inhibitor of two proteins responsible for glucose regulation known as sodium-glucose co-transporter types 1 and 2 (SGLT1 and SGLT2). SGLT1 is responsible for glucose absorption in the gastrointestinal tract, and SGLT2 is responsible for glucose reabsorption by the kidney. Sotagliflozin has been shown in a Phase 2 study to improve glycemic control in people with type 1 diabetes while reducing their need for mealtime insulin. 

Lexicon entered into a collaboration and license agreement with Sanofi in November 2015 under which Lexicon granted Sanofi an exclusive, worldwide (excluding Japan), royalty-bearing right and license to develop, manufacture and commercialize sotagliflozin. Lexicon is responsible for all clinical development activities relating to type 1 diabetes and retains an exclusive option to co-promote and have a significant role, in collaboration with Sanofi, in the commercialization of sotagliflozin for the treatment of type 1 diabetes in the U.S. Sanofi is responsible for all clinical development and commercialization of sotagliflozin for the treatment of type 2 diabetes worldwide (excluding Japan) and is solely responsible for the commercialization of sotagliflozin for the treatment of type 1 diabetes outside the U.S. (excluding Japan).

About Lexicon Pharmaceuticals

Lexicon is a fully integrated biopharmaceutical company that is applying a unique approach to gene science based on Nobel Prize-winning technology to discover and develop precise medicines for patients with serious, chronic conditions. Through its Genome5000™ program, Lexicon scientists have studied the role and function of nearly 5,000 genes over the last 20 years and have identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to safely and effectively treat disease. In addition to its recently-launched product for carcinoid syndrome diarrhea, XERMELO™ (telotristat ethyl), Lexicon has a pipeline of promising drug candidates in clinical and pre-clinical development in diabetes and metabolism and neuropathic pain. For additional information please visit www.lexpharma.com.

Safe Harbor Statement

This press release contains "forward-looking statements," including statements relating to Lexicon's and its licensees' clinical development of and regulatory filings for sotagliflozin and the results and projected timing of clinical trials and the potential therapeutic and commercial potential of sotagliflozin. In addition, this press release also contains forward-looking statements relating to Lexicon's growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including the risk that clinical studies of sotagliflozin may be halted, delayed or otherwise not demonstrate safety or efficacy, the risk that the FDA and other regulatory authorities may not grant regulatory approval of sotagliflozin in accordance with Lexicon's currently anticipated timelines or at all, and the risk that such regulatory approvals, if granted, may have significant limitations on the approved use of sotagliflozin. As a result, sotagliflozin may never be successfully commercialized. Other risks include Lexicon's ability to meet its capital requirements, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of its other potential drug candidates, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon's actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under "Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2016, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

SOURCE Lexicon Pharmaceuticals, Inc.

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