Lexicon Pharmaceuticals Reports Additional Positive Data From Pivotal Phase 3 inTandem2 Study Of Sotagliflozin

THE WOODLANDS, Texas, Aug. 15, 2017 /PRNewswire/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced today additional positive data from the pivotal Phase 3 inTandem2 study of sotagliflozin, an investigational dual SGLT1 and SGLT2 inhibitor. It was previously announced that both doses of sotagliflozin achieved the primary endpoint of the inTandem2 study, showing statistically significant reductions in A1C at 24 weeks in adult patients with type 1 diabetes on a background of optimized insulin. The new data showed that the A1C benefit was sustained over 52 weeks as well as achievement of all secondary endpoints for both sotagliflozin doses. These results of the inTandem2 study, conducted primarily in Europe, replicated results previously reported from Lexicon's Phase 3 inTandem1 study of sotagliflozin in type 1 diabetes patients, conducted in North America.

Notably, the outcome on every secondary endpoint favored sotagliflozin over placebo, with statistically significant results for all six secondary endpoints for both doses:

• net benefit (proportion of patients with A1C <7.0% at Week 24 and no episode of severe hypoglycemia and no episode of diabetic ketoacidosis (DKA);
• body weight;
• bolus insulin use;
• fasting plasma glucose (FPG);
• Diabetes Treatment Satisfaction Questionnaire status (DTSQs) score; and
• 2-item Diabetes Distress Screening Scale (DDS2) questionnaire score.

Systolic blood pressure (SBP) in the subset of type 1 diabetic patients in the study with baseline hypertension (SBP ≥130 mmHg) was also statistically significantly reduced with the 400 mg dose compared with placebo.

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.  

"InTandem2 is the second pivotal study to demonstrate sotagliflozin's ability to durably improve both A1C and other key measures of health such as body weight and blood pressure in patients with type 1 diabetes. Today's results underscore sotagliflozin's benefit/risk profile and highlight its differentiated profile in the type 1 diabetes landscape," said Pablo Lapuerta, M.D., Lexicon's executive vice president and chief medical officer. "We look forward to presenting more detailed results from the inTandem2 study at an upcoming medical conference."

"Today's results are exciting for so many people living with type 1 diabetes," said Thomas Danne, M.D., Head of the Diabetes Center at the Children's Hospital on the Bult in Hannover, Germany and primary investigator for the inTandem2 clinical trial. "The observation that sotagliflozin significantly lowers blood glucose and favorably affects body weight and blood pressure without an increase in hypoglycemia strengthens the potential of the drug to become a first-in-class therapy in the treatment paradigm for type 1 diabetes."

About inTandem2

The Phase 3 study known as inTandem2 was a double-blind, placebo-controlled, multi-center study of 782 patients in Europe and Israel 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 levels after the six-week optimization period were 7.79%, 7.74% and 7.71% for patients randomized to the placebo, 200mg and 400mg arms, respectively.

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 258 patients in the placebo arm, 261 patients in the 200mg dose arm and 263 patients in the 400mg dose arm.  The overall mean placebo-adjusted A1C reduction at week 24 was 0.37% in the 200mg dose arm (p<0.001) and 0.35% in the 400mg dose arm (p<0.001). The A1C benefit achieved with sotagliflozin was sustained with statistically-significant results over the full 52-week duration of the study for both the 200 mg and 400 mg doses.

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 61.2%, 68.2% and 68.8%, respectively; the incidences of SAEs were 6.6%, 10.0% and 8.0%, respectively; and discontinuations due to AEs were 3.5%, 3.8% and 6.8%, respectively. There were two deaths 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 13 (5.0%), 13 (5.0%), and 6 (2.3%) 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 0 (0.0%), 6 (2.3%), and 9 (3.4%) in the placebo, 200 mg and 400 mg dose arms, respectively. 

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 has exercised its option to co-promote and to 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 first commercial product, 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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