Study Conducted in Young Adults with Type 1 Diabetes and High Baseline A1C
The Woodlands, Texas, December 5, 2016 – Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced top-line results today from a Phase 2 clinical study of sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, conducted by Lexicon in collaboration with JDRF, the leading global organization funding type 1 diabetes research.
The purpose of this Phase 2 clinical trial, which randomized a total of 87 patients, was to assess the effects of a once-daily 400 mg dose of sotagliflozin compared to a placebo control in insulin-treated young adults with type 1 diabetes, aged 18-30 years, and particularly high baseline A1C levels of greater than or equal to 9.0%, representative of an at-risk population in which glycemic control and adherence to therapy are substantial challenges. The study promoted adherence and encouraged insulin adjustment as needed to achieve glucose control targets.
Patients treated with sotagliflozin as an adjunct to insulin had a mean reduction from baseline in A1C of 1.33% after 12 weeks of treatment. The results for the A1C primary endpoint numerically favored sotagliflozin, with a placebo-adjusted reduction of 0.35%, but did not reach statistical significance. A pre-planned subgroup analysis in patients with A1C at baseline of less than or equal to 10.0% showed a statistically-significant reduction in this same A1C primary endpoint, with sotagliflozin-treated patients achieving a mean reduction from baseline in A1C of 1.43% and a placebo-adjusted reduction of 0.75% (p=0.006). In secondary measures:
- Patients treated with sotagliflozin achieved an increase of approximately one-third in the mean proportion of time spent in the target range of 70-180 mg/dL (from 33.1% at baseline to 43.6% at week 12) as measured by continuous glucose monitoring (CGM), as compared to a slight reduction in time in the target range (from 33.5% at baseline to 32.9% at week 12) for patients treated with placebo.
- Patients treated with sotagliflozin achieved a mean placebo-adjusted reduction from baseline to week 12 of 56.6 mg/dL in two-hour post-prandial glucose (PPG) following a standardized mixed meal.
- Patients treated with sotagliflozin achieved a mean reduction of 0.62 kg in body weight from baseline to week 12, as compared to an increase of 1.75 kg in body weight for patients treated with placebo.
Sotagliflozin was well tolerated in the study, with a smaller proportion of patients on sotagliflozin experiencing treatment-emergent adverse events (AEs) (58.1% on sotagliflozin vs. 61.9% on placebo) and serious AEs (SAEs) (4.7% on sotagliflozin vs. 7.1% on placebo). There were no discontinuations from study drug due to AEs on sotagliflozin vs. two patients on placebo. One patient in the sotagliflozin treated arm and two patients in the placebo arm experienced a severe hypoglycemia event during the 12-week treatment period. No patients treated with sotagliflozin experienced a diabetic ketoacidosis (DKA) event, whereas one placebo-treated patient experienced a DKA event during the 12-week treatment period and two additional patients experienced a DKA event during the pre-randomization, placebo run-in period of the study. There were no deaths in the study.
“Sotagliflozin demonstrated favorable safety in this study in an at-risk population and continues to show evidence of improvements in the quality of glucose control consistent with its mechanism of action,” said Pablo Lapuerta, M.D., Lexicon’s executive vice president and chief medical officer. “Reductions in post-prandial glucose were consistent with SGLT1 inhibition in the gastrointestinal tract. Better control of post-prandial glucose will allow patients with type 1 diabetes to spend more time with glucose in a better range, with low rates of severe hypoglycemia.”
“We applaud the efforts of Lexicon in prioritizing the development of novel therapies for the multitudes affected by type 1 diabetes. Individuals with type 1 diabetes continue to experience challenges of disease burden and high levels of A1C, and we expect at least a subset of those to benefit from novel, add-on therapies to elicit additional glycemic and metabolic benefits,” said Sanjoy Dutta, Ph.D., associate vice president, Translational Development and International Partnerships at JDRF. “We are looking forward to seeing new options for individuals with type 1 diabetes, and we truly value our partnership with Lexicon as we drive our vision of a world without type 1 diabetes.”
About the JDRF Phase 2 Clinical Trial
The double-blind, placebo controlled, Phase 2 study randomized 87 patients, aged 18 to 30, in the United States with type 1 diabetes on insulin pump or multiple daily injection therapy who had an A1C level entering the study greater than or equal to 9.0%. The study evaluated a once-daily 400 mg dose of sotagliflozin, before the first meal of the day, against placebo. Prior to randomization, there was a two-week run-in period in which patients received placebo in addition to insulin. After completion of the run-in period, patients were randomized to either sotagliflozin or placebo. The mean A1C level at baseline, after the two-week run-in period, was 9.9% in the sotagliflozin-treated arm and 9.7% in the placebo arm. Following randomization, adjustments in insulin doses were made when needed in the medical judgment of the investigator. During the 12-week treatment period, total insulin use increased in the placebo arm and decreased in the sotagliflozin arm; basal insulin use increased in both the placebo and sotagliflozin arms, with a greater increase in the placebo arm; and bolus insulin use decreased in both the placebo and sotagliflozin arms, with a greater decrease in the sotagliflozin arm.
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, 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 United States. Sanofi is responsible for all clinical development and commercialization of sotagliflozin for the treatment of type 2 diabetes worldwide and is solely responsible for the commercialization of sotagliflozin for the treatment of type 1 diabetes outside the United States.
Lexicon announced positive top-line results of its first pivotal Phase 3 clinical trial of sotagliflozin in patients with type 1 diabetes, on a background of optimized insulin (inTandem1), in September 2016. Lexicon is conducting a second pivotal Phase 3 clinical trial (inTandem2) from which top-line results are expected later this month. A third type 1 diabetes Phase 3 clinical trial, inTandem3, is underway globally and is studying approximately 1,400 patients treated with sotagliflozin 400 mg once daily or placebo on a background of any insulin therapy, but without insulin optimization prior to randomization. Sanofi is expected to commence Phase 3 clinical trials for sotagliflozin in patients with type 2 diabetes this year.
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. Lexicon has a pipeline of promising drug candidates in clinical and pre-clinical development in oncology, diabetes and metabolism. For additional information please visit www.lexpharma.com.
JDRF is the leading global organization funding type 1 diabetes (T1D) research. JDRF’s mission is to accelerate life-changing breakthroughs to cure, prevent and treat T1D and its complications. To accomplish this, JDRF has invested nearly $2 billion in research funding since its inception. JDRF is an organization built on a grassroots model of people connecting in their local communities, collaborating regionally for efficiency and broader fundraising impact, and uniting on a national stage to pool resources, passion, and energy. JDRF collaborates with academic institutions, policymakers, and corporate and industry partners to develop and deliver a pipeline of innovative therapies to people living with T1D. JDRF’s staff and volunteers throughout the United States and its six international affiliates are dedicated to advocacy, community engagement and its vision of a world without T1D. For more information, please visit jdrf.org or follow us on Twitter: @JDRF.
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 (LX4211) 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, 2015, 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.