Sotagliflozin Data from Pivotal inTandem1 and inTandem2 Studies in Patients with Type 1 Diabetes Presented at ADA 2017

THE WOODLANDS, Texas, June 10, 2017 /PRNewswire/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced data from its two pivotal sotagliflozin studies, inTandem1 and inTandem2, being presented at the 77^th American Diabetes Association (ADA) Scientific Sessions in San Diego, CA.

Collectively, 24-week data from the two pivotal inTandem1 and inTandem2 studies for sotagliflozin in patients with type 1 diabetes demonstrated the following:

• Sotagliflozin 200 mg and 400 mg on top of optimized insulin significantly reduced A1C compared to placebo (p<0.001 in both studies).

• Sotagliflozin was generally well tolerated. In both studies, there was a low rate of severe hypoglycemia, which occurred less frequently on sotagliflozin than placebo in three of four arms across the two studies.  In both studies, there was a low diabetic ketoacidosis (DKA) rate (0.4% to 3.1% over 24 weeks) that was higher for patients on insulin pump versus multiple dose injections (MDI).

inTandem1 Study – "Twenty-Four Week Efficacy and Safety of Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes" (#69-OR)

• inTandem1 met its primary endpoint of change in A1C from baseline after a 24-week treatment period. The percentage reduction in A1C from baseline after 24 weeks of treatment were 0.08%, 0.43% and 0.49% for placebo, 200 mg, and 400 mg, respectively. The difference compared to placebo for patients treated with sotagliflozin 200 mg and 400 mg once daily were 0.36% and 0.41%, respectively (p<0.001 for both doses).

• All secondary endpoints, including net benefit (A1C <7.0% with no episode of severe hypoglycemia and no episode of DKA), weight, bolus insulin, fasting plasma glucose (FPG) and two patient-reported outcomes, were statistical significant in the 400 mg arm. Net benefit and weight were statistical significant in the 200 mg arm as well.

• Sotagliflozin was generally well tolerated. Across all three dose arms, the incidence of treatment-emergent adverse events (TEAEs) over 24 weeks of treatment was 67.5%, 67.3% and 71.0% on placebo, 200 mg and 400 mg, respectively. The incidence of serious adverse events (SAEs) was 3.4%, 3.8% and 6.9% on placebo, 200 mg and 400 mg, respectively. Discontinuations due to AEs were 1.5%, 1.1% and 3.8% on placebo, 200 mg and 400 mg, respectively. There were no deaths reported in the study.

• There was no increase in severe hypoglycemic events during the 24-week treatment period (18 (6.7%), 11 (4.2%) and 12 (4.6%) in the placebo, 200 mg and 400 mg dose arms, respectively). There was a 0.4% rate of discontinuation due to severe hypoglycemia in the placebo arm and no discontinuations in the 200 mg and 400 mg drug arms.

• The number of patients with severe hypoglycemic events on insulin pump was 7 (4.4%), 7 (4.5%) and 10 (6.4%) in the placebo, 200 mg and 400 mg dose arms, respectively. The number of patients with severe hypoglycemic events on MDI was 11 (10.2%), 4 (3.7%) and 2 (1.9%) in the placebo, 200 mg and 400 mg dose arms, respectively.

• The number of patients positively adjudicated with DKA events during the 24-week treatment period was 0 (0.0%), 3 (1.1%) and 8 (3.1%) in the placebo, 200 mg and 400 mg dose arms, respectively, with a discontinuation rate due to DKA events of 0.0%, 0.4% and 0.8%, respectively.

• The number of positively adjudicated DKA events through Week 24 were more common with patients on pump compared to patients using MDI (pump: 0 patients (0.0%) for placebo, compared to 2 (1.3%) and 6 (3.8%) for 200 mg and 400 mg, respectively; MDI: 0 (0.0%) for placebo, compared to 1 (0.9%) and 2 (1.9%) for 200 mg and 400 mg, respectively). The majority of DKA cases in the 400 mg arm had blood glucose levels of <250 mg/dL.

inTandem2 Study – "Twenty- Four–Week Efficacy and Safety of Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes" (poster #146-LB)

• The percentage reduction in A1C from baseline after 24 weeks of treatment were 0.03%, 0.39% and 0.37% for placebo, 200 mg and 400 mg, respectively (p=0.54, p<0.001 and p<0.001, respectively). The difference compared to placebo for patients treated with sotagliflozin 200 mg and 400 mg once daily were 0.36% and 0.35%, respectively (p<0.001 for both doses).

• Sotagliflozin 200 mg and 400 mg compared to placebo achieved statistical significance (p<0.001) on the net benefit endpoint (AIC <7.0% with no episode of severe hypoglycemia and no episode of DKA).

• Sotagliflozin was generally well tolerated. Across all three dose arms, the incidence of treatment-emergent adverse events (TEAEs) over 24 weeks of treatment was 51.4%, 55.9% and 54.4% on placebo, 200 mg and 400 mg, respectively. The incidence of serious adverse events (SAEs) was 3.5% on placebo and 4.2% on both 200 mg and 400 mg. Discontinuations due to AEs were 1.6%, 1.9% and 3.0% on placebo, 200 mg and 400 mg, respectively. There were two deaths reported in the placebo arm and no deaths in the 200mg and 400 mg arms.

• There was no dose-related increase in the rate of severe hypoglycemia during the 24-week treatment period (7 (2.7%), 10 (3.8%) and 6 (2.3%) in the placebo, 200 mg and 400 mg dose arms, respectively). There were no discontinuations due to severe hypoglycemia in any of the study arms.

• The number of patients with severe hypoglycemic events on insulin pump was 2 (3.0%), 4 (5.9%) and 3 (4.5%) in the placebo, 200 mg and 400 mg dose arms, respectively. The number of patients with severe hypoglycemic events on MDI was 5 (2.6%), 6 (3.1%) and 3 (1.5%) in the placebo, 200 mg and 400 mg dose arms, respectively.

• The number of patients positively adjudicated with DKA events during the 24-week treatment period was 0 (0.0%), 1 (0.4%) and 3 (1.1%) in the placebo, 200 mg and 400 mg dose arms, respectively, with a discontinuation rate due to DKA events of 0.0%, 0.0% and 0.8%, respectively.

• The number of positively adjudicated DKA events through Week 24 were more common with patients on pump compared to patients using MDI or placebo (pump: 0 patients (0.0%) for placebo, compared to 0 (0.0%) and 3 (4.5%) for 200 mg and 400 mg, respectively; MDI: 0 (0.0%) for placebo, compared to 1 (0.5%) and 0 (0.0%) for 200 mg and 400 mg, respectively).

"There remains a need for oral therapeutic agents in addition to insulin to help improve quality of life in patients with type 1 diabetes by reducing the diabetes management burden and sotagliflozin has that potential," 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. "Sotagliflozin has demonstrated, in three Phase 3 studies, the ability for patients to achieve glycemic goals with a safety profile that supports its utility in the type 1 diabetes community."

"We are extremely pleased with the results achieved by sotagliflozin in its three Phase 3 studies," said Lonnel Coats, Lexicon's president and chief executive officer. "We look forward to seeing the pooled continuous glucose monitoring data from inTandem1 and inTandem2 as well as data from secondary endpoints in inTandem2 in the third quarter."

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. 

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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