"These top-line results confirm the results we announced earlier this year from our first pivotal Phase 3 study of sotagliflozin," said Lexicon president and chief executive officer, Lonnel Coats. "We are extremely pleased with the results in both of these Phase 3 studies and are enthusiastic about the potential benefits that sotagliflozin may bring to people with type 1 diabetes."
"The inTandem2 study demonstrated a compelling safety and efficacy profile for sotagliflozin in adults living with type 1 diabetes," said Thomas Danne, M.D., Head of the Center for Children Endocrinology and Diabetes at the Children's Hospital on the Bult in Hannover, Germany and primary investigator for the inTandem2 clinical trial. "The potential to significantly lower A1C levels without an increase in hypoglycemia would represent a major shift in the treatment paradigm for type 1 diabetes."
The double-blind, placebo controlled, Phase 3 study known as inTandem2 randomized 782 adult 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 7.80%, 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 has a double-blind long term extension of 28 weeks, with a total treatment duration of 52 weeks. There were 257 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 0.36% in the 200mg dose arm (p<0.001) and 0.35% in the 400mg dose arm (p<0.001).
Sotagliflozin was generally well tolerated. Across all three dose arms (placebo, 200mg, 400mg), the incidences of treatment-emergent adverse events (AEs) were 51.4%, 55.9% and 54.4%, respectively; the incidences of serious AEs (SAEs) were 3.5%, 4.2% and 4.2%, respectively; and discontinuations due to AEs were 1.6%, 1.9% and 3.0%, 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 diabetic ketoacidosis (DKA). The number of patients with severe hypoglycemic events during the 24-week treatment period was seven (2.7%), ten (3.8%), and six (2.3%) in the placebo, 200mg and 400mg dose arms, respectively. The number of patients with DKA events during the 24-week treatment period was none (0.0%), one (0.4%), and three (1.1%) in the placebo, 200mg and 400mg dose arms, respectively.
Lexicon is conducting a third Phase 3 clinical trial in type 1 diabetes patients, inTandem3, which is studying approximately 1,400 patients treated with sotagliflozin 400mg once daily or placebo on a background of any insulin therapy, but without insulin optimization prior to randomization. Sanofi is responsible for conducting the Phase 3 clinical trials for sotagliflozin in patients with type 2 diabetes.
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 the primary transporter for absorption of glucose and galactose in the gastrointestinal tract, and SGLT2 is primarily 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, 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 in the licensed territory and is solely responsible for the commercialization of sotagliflozin for the treatment of type 1 diabetes outside the United States.
Lexicon Conference Call
Lexicon management will hold a conference call and webcast to discuss the inTandem2 Phase 3 top-line results at 8:30 a.m. Eastern Time on December 21, 2016. The dial-in number for the conference call is 888-645-5785 (within the US/Canada) or 970-300-1531 (international). The conference ID for all callers is 43517998. Investors can access a live webcast of the call at www.lexpharma.com. An archived version of the webcast will be available on the website through January 21, 2017.
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.
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.
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SOURCE Lexicon Pharmaceuticals, Inc.