New England Journal Of Medicine Publishes Data From Phase 3 inTandem3 Study Of Sotagliflozin In Patients With Type 1 Diabetes

THE WOODLANDS, Texas, Sept. 13, 2017 /PRNewswire/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that the New England Journal of Medicine (NEJM) published the results of the Phase 3 inTandem3 study of sotagliflozin, an investigational dual SGLT1 and SGLT2 inhibitor, for the treatment of patients with type 1 diabetes on any background insulin therapy. The data were published online today in conjunction with presentation of these data at the European Association for the Study of Diabetes (EASD) 53^rd annual meeting (September 11-15, Lisbon, Portugal) in a session titled, "The Phase 3 inTandem clinical program:  efficacy and safety of sotagliflozin in adults with type 1 diabetes."

The study met its primary endpoint with statistical significance, demonstrating the superiority of sotagliflozin 400 mg compared to placebo in the proportion of patients with A1C <7.0% at Week 24 and no episode of severe hypoglycemia and no episode of DKA after randomization. The responder rate for patients on sotagliflozin was approximately twice the rate as compared to placebo. The difference compared to placebo for patients treated with sotagliflozin was 13.4% (p<0.001).

"The clinically meaningful and statistically significant effects of sotagliflozin on glucose control (A1C) were achieved with a similar rate of severe hypoglycemia while reducing weight and blood pressure in hypertensive patients with type 1 diabetes. The combination of these effects provides a differentiated drug profile and the opportunity for sotagliflozin to transform the treatment paradigm as a novel oral adjunct to insulin therapy in this patient population," said Satish Garg, M.D., lead investigator of inTandem3, Professor of Medicine and Pediatrics and Director Adult Program at the Barbara Davis Center for Diabetes, University of Colorado Denver and Editor-in-Chief, Diabetes Technology and Therapeutics. "Managing type 1 diabetes can be very challenging for patients and their caregivers and as a clinician treating patients with this condition, these positive results bring promise for our ability to improve lives."

The outcome on every secondary endpoint achieved statistical significance favoring sotagliflozin over placebo, including change from baseline in A1C, body weight, systolic blood pressure (SBP) in patients with baseline SBP ?130 mm Hg and bolus insulin.

Sotagliflozin significantly reduced A1C compared to placebo after 24 weeks of treatment. The least squares (LS) mean reduction in A1C from baseline was 0.79% and 0.33% for sotagliflozin and placebo, respectively. The difference compared to placebo for patients treated with sotagliflozin was 0.46% (p<0.001).

Patients taking sotagliflozin experienced an LS mean reduction from baseline in body weight after 24 weeks of treatment of 2.2 kg compared to a mean body weight gain of 0.8 kg for patients on placebo (p<0.001 for sotagliflozin and placebo). The reduction in LS means compared to placebo for patients treated with sotagliflozin was 3.0 kg (p<0.001).

Systolic blood pressure in the subset of type 1 diabetic patients in the study with baseline hypertension (SBP ?130 mm Hg) was reduced by 9.2 mm Hg at Week 16 when treated with sotagliflozin compared to a reduction of 5.7 mm Hg on placebo (p<0.001 for sotagliflozin and placebo). The reduction in LS means compared to placebo for patients treated with sotagliflozin was 3.5 mm Hg (p=0.002).

Sotagliflozin significantly reduced the amount of bolus insulin used compared to placebo after 24 weeks of treatment. The reduction in bolus insulin from baseline was 3.9 IU per day and 1.1 IU per day for sotagliflozin and placebo, respectively (p<0.001 and p=0.02, respectively). The reduction in LS means compared to placebo for patients treated with sotagliflozin was 2.8 IU per day (p<0.001).

Sotagliflozin demonstrated a generally well tolerated safety profile during a 24-week treatment period, with rates of treatment-emergent adverse events, serious adverse events, and discontinuations due to adverse events that were consistent with rates seen in two prior pivotal Phase 3 studies, inTandem1 and inTandem2, including a similar rate of severe hypoglycemia for the sotagliflozin arm compared to placebo during the 24-week treatment period (3.0% for sotagliflozin compared to 2.4% for placebo). There was a higher rate of DKA during the 24-week treatment period for sotagliflozin (3.0%) than placebo (0.6%). Other adverse events of special interest included diarrhea (sotagliflozin 4.1%, placebo 2.3%) and genital mycotic infection (sotagliflozin 6.4%, placebo 2.1%).

"We are extremely proud to have the inTandem3 results published in such a prestigious journal, which will raise much-needed awareness of type 1 diabetes in the medical community," said Lonnel Coats, Lexicon's president and chief executive officer. "Collectively, today's positive findings as well as data from our two pivotal trials underline the importance and relevance of the dual SGLT1 and SGLT2 inhibitor mechanism of action in diabetes. As we remain committed to advancing the science in diabetes and bringing innovative therapies to patients to help improve outcomes and ease the burden of managing their diabetes, we look forward to Sanofi's filing for global regulatory approval for type 1 diabetes in the first half of 2018."

"Despite treatment with insulin analogues, approximately 70% of patients with type 1 diabetes do not reach the desired glycemic A1C target of <7.0%," said Juliana Oliveira, Vice President and Global Project Head for Sotagliflozin, Sanofi. "These outcomes further highlight the large unmet need for new oral medications that can be added to insulin, and publication of these results in the New England Journal of Medicine will increase awareness of this need."

Conference Call and Webcast Information

Lexicon management will hold a live conference call and webcast today at 8:00 am EDT / 7:00 am CDT to provide an update on the sotagliflozin program from EASD. The dial-in number for the conference call is 888-645-5785 (U.S./Canada) or 970-300-1531 (international). The conference ID for all callers is 84533796. The live webcast and replay may be accessed by visiting Lexicon's website at www.lexpharma.com/investors. An archived version of the webcast will be available on the website for 14 days.

About inTandem3

The Phase 3 study known as inTandem3 was a global, randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 1,405 patients with type 1 diabetes on any background insulin therapy who had an A1C level entering the study between 7.0% and 11.0%. Patients had a confirmed diagnosis of type 1 diabetes and inadequate glycemic control on insulin therapy alone. The study evaluated 400 mg of sotagliflozin versus placebo taken once daily before the first meal of the day. The primary objective of the study was to demonstrate the superiority of sotagliflozin 400 mg versus placebo in the proportion of patients with glycosylated A1C <7.0% at Week 24 and no episode of severe hypoglycemia and no episode of DKA after randomization. Secondary endpoints included change from baseline in A1C, body weight, systolic blood pressure (SBP) in patients with baseline SBP ?130 mm Hg and bolus insulin.

About Sotagliflozin

Discovered using Lexicon's unique approach to gene science, sotagliflozin is an investigational 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 has exercised 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 Genome5000tm 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.