SGLT1

THE WOODLANDS, Texas, March 25, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that four data presentations related to sotagliflozin, an inhibitor of two sodium glucose transport proteins (SGLT2 and SGLT1), will be delivered during the American College of Cardiology 73rd Annual Scientific Session & Expo being held April 6 - 8, 2024 in Atlanta, Georgia, including results from a post-hoc evaluation of the efficacy of sotagliflozin in reducing stroke events in patients with type 2 diabetes, chronic kidney disease (CKD), and high cardiovascular (CV) risk in the SCORED Phase 3 clinical trial. “Following FDA’s 2023 approval of INPEFA® (sotagliflozin) for heart failure (HF), researchers are adding to the overall scientific understanding of sotagliflozin, including clinical evidence of its ability to reduce the risk of stroke and myocardial infarction (MI), or heart attack,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. Details of the presentations are as follows: Sotagliflozin Reduces Stroke Outcomes in Patients with Diabetes and Chronic Kidney Disease – a moderated poster presentation, Monday, April 8, 12:15 - 12:25 p.m. ET, Theater 8‚ presented by Rahul Aggarwal, M.D., Icahn School of Medicine at Mount Sinai, New York, New YorkStudy researchers evaluated the efficacy of sotagliflozin in reducing all-cause and cause-specific stroke outcomes among patients with type 2 diabetes, CKD, and high CV risk. In a post-hoc analysis of data from the 10,584 patients in the SCORED Phase 3 clinical trial, 213 all-cause stroke events occurred, including 29 (13.6%) fatal events. Sotagliflozin reduced the risk of all-cause stroke by 34%, with 1.2 events per 100 patient-years in the sotagliflozin group and 1.8 events per 100 patient-years in the placebo group. Similarly, sotagliflozin reduced the risk of ischemic stroke by 32%, with 0.8 events per 100 patient-years in the sotagliflozin group and 1.2 events per 100 patient-years in the placebo group.Click here to access additional study details in the online abstract. Sotagliflozin, a Dual SGLT 1 and 2 Inhibitor, Modulated Expression of Glucose Transport and Inflammatory Proteins in Endothelial Cells following Angiotensin II Stimulation – a poster presentation, Sunday, April 7, 1:15 – 2:00 p.m. ET, 1425-157, Hall B4-5, presented by Preston Mason, Ph.D. MBA, Elucida Research, Beverly, MassachusettsStudy researchers found that sotagliflozin modulated expression of proteins linked to the Akt signaling pathway, glucose transport and vasodilation in human endothelial cells exposed to an inflammatory stimulus in vitro. The favorable endothelial cell actions of sotagliflozin during inflammation add to the body of knowledge of sotagliflozin’s mechanism of action and are consistent with the reduced atherothrombotic risk demonstrated in outcome trials.Click here to access additional study details in the online abstract. Sotagliflozin, a First-in-Class SGLT1/2 Inhibitor, Inhibits Clotting Potential in the Vessel via Inhibition of Platelet Activation, Integrin Activation, and Aggregation in Human Platelets – a moderated poster presentation, Sunday, April 7, 11:30 - 2:40 a.m. ET, Theater 5‚ presented by Livia Stanger, Ph.D. Candidate, University of Michigan, Ann Arbor, MichiganStudy researchers found that sotagliflozin inhibits platelet activation through simultaneously targeting SGLT1 and SGLT2. These findings provide insight into the potential mechanism by which sotagliflozin impacts stroke and MI risk in patients with type 2 diabetes and CKD and provides a basis for further studies to explore the role of sotagliflozin for CV protection in patients at increased risk for ischemic events.Click here to access study details in the online abstract. Temporal Shift in Heart Failure Medications Prescribed to Hospitalized Patients According to Sex and Age. Results from Two Large US Integrated Health Systems – a poster presentation, Sunday, April 7, 9:15 – 10:00 a.m. ET, 1343-121, Hall B4-5, presented by Mario Enrico Canonico, M.D., Ph.D., CPC Clinical Research, University of Colorado, Aurora, ColoradoStudy researchers found that substantial opportunity exists to further improve the prescription of guideline-directed medical therapy (GDMT) for patients with HF. Differences in timing of initiation of these therapies by sex and age highlight the need to evaluate care gaps by these and other determinants of health.Click here to access additional study details in the online abstract. On May 26, 2023, the U.S. Food and Drug Administration approved INPEFA® (sotagliflozin), a once-daily oral tablet, to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure ortype 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. About Lexicon Pharmaceuticals Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through its Genome5000™ program, Lexicon scientists studied the role and function of nearly 5,000 genes and 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 treat diseases safely and effectively. Lexicon has advanced multiple medicines to market and has a pipeline of promising drug candidates in heart failure, neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit www.lexpharma.com. About INPEFA® (sotagliflozin) Discovered using Lexicon’s unique approach to gene science, INPEFA® (sotagliflozin) is an oral inhibitor of two proteins responsible for glucose regulation known as sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose reabsorption by the kidney and SGLT1 is responsible for glucose absorption in the gastrointestinal tract. INPEFA has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients. INDICATION INPEFA is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure ortype 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors IMPORTANT SAFETY INFORMATION Dosing: Assess renal function and volume status and, if necessary, correct volume depletion prior to initiation of INPEFA. INPEFA dosing for patients with decompensated heart failure may begin when patients are hemodynamically stable, including when hospitalized or immediately upon discharge. Contraindications: INPEFA is contraindicated in patients with hypersensitivity to any component. Warnings and Precautions: Ketoacidosis: INPEFA increases the risk of ketoacidosis in patients with type 1 diabetes mellitus (T1DM). Type 2 diabetes mellitus (T2DM) and pancreatic disorders are also risk factors. The risk of ketoacidosis may be greater with higher doses. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes using sodium glucose transporter 2 (SGLT2) inhibitors. Before initiating INPEFA, assess risk factors for ketoacidosis. Consider ketone monitoring in patients with T1DM and consider ketone monitoring in others at risk for ketoacidosis, and educate patients on the signs/symptoms of ketoacidosis. Patients receiving INPEFA may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis. Assess patients who present with signs and symptoms of metabolic acidosis or ketoacidosis, regardless of blood glucose level. If suspected, discontinue INPEFA, evaluate, and treat promptly. Monitor patients for resolution of ketoacidosis before restarting INPEFA. Volume Depletion: INPEFA can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors. Patients with impaired renal function (eGFR < 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating INPEFA in patients with one or more of these characteristics, assess volume status and renal function, and monitor for signs and symptoms of hypotension during therapy. Urosepsis and Pyelonephritis: Treatment with SGLT2 inhibitors, including INPEFA, increases the risk for urinary tract infections. Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly. Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Insulin and insulin secretagogues are known to cause hypoglycemia. INPEFA may increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used with INPEFA. Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Reports of Fournier’s Gangrene, a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in post-marketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors. Assess patients who present with pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue INPEFA, closely monitor patient signs and symptoms, and provide appropriate alternative therapy for heart failure. Genital Mycotic Infections: INPEFA increases the risk of genital mycotic infections. Monitor and treat as appropriate. Urinary Glucose Test and 1,5-anhydroglucitol (1,5-AG) Assay: these are not reliable for patients taking SGLT2 inhibitors. Use alternative testing methods to monitor glucose levels. Common Adverse Reactions: the most commonly reported adverse reactions (incidence ≥ 5%) were urinary tract infection, volume depletion, diarrhea, and hypoglycemia. Drug Interactions: Digoxin: Monitor patients appropriately as there is an increase in the exposure of digoxin when coadministered with INPEFA 400 mg.Uridine 5'-diphospho-glucuronosyltransferase (UGT) Inducer: The coadministration of rifampicin, an inducer of UGTs, with sotagliflozin resulted in a decrease in the exposure of sotagliflozin.Lithium: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during INPEFA initiation and with dosage changes. Use in Specific Populations: Pregnancy and Lactation: INPEFA is not recommended during the second and third trimesters of pregnancy, nor while breastfeeding.Geriatric Use: No INPEFA dosage change is recommended based on age. No overall differences in efficacy were detected between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be at increased risk for volume depletion adverse reactions, including hypotension.Renal Impairment: INPEFA was evaluated in patients with chronic kidney disease (eGFR 25 to 60 mL/min/1.73 m2) and in patients with heart failure with eGFR <60 mL/min/1.73 m2. The safety profile of INPEFA across eGFR subgroups in these studies was consistent with the known safety profile. There was an increase in volume-related adverse events (e.g., hypotension, dizziness) in patients with eGFR <30 mL/min/1.73m2 relative to the overall safety population. Efficacy and safety studies with INPEFA did not enroll patients with an eGFR less than 25 mL/min/1.73 m2 or on dialysis. After starting therapy in the studies, patients were discontinued if eGFR fell below 15 mL/min/1.73 m2 or were initiated on chronic dialysis.Hepatic Impairment: INPEFA is not recommended in patients with moderate or severe hepatic impairment. Click here for full Prescribing Information. Safe Harbor Statement This press release contains “forward-looking statements,” including statements relating to the therapeutic and commercial potential, research and clinical development and regulatory status of INPEFA® (sotagliflozin). In addition, this press release also contains forward looking statements relating to Lexicon’s financial position and long-term outlook on its business, 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 Lexicon’s ability to meet its capital requirements, successfully commercialize INPEFA in heart failure on the timeline and/or at the prices currently contemplated or at all, conduct preclinical and clinical development and obtain necessary regulatory approvals of INPEFA (in other indications), LX9211 and its other drug candidates on its anticipated timelines, 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, 2023 and other subsequent disclosure documents 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. For Investor Inquiries:Lisa DeFrancescoLexicon Pharmaceuticals, Inc.lexinvest@lexpharma.com For Media Inquiries:Alina CocuzzaLexicon Pharmaceuticals, Inc.acocuzza@lexpharma.com

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。近日，生物制药公司Lexicon Pharmaceuticals， Inc.（纳斯达克股票代码：LXRX）宣布，在收到 FDA 的最新反馈后，它正准备重新提交SGLT1/2抑制剂索格列净作为胰岛素治疗1型糖尿病和慢性肾病(CKD)患者的辅助药物的新药申请 （NDA）。重新提交计划于年中进行，预计监管审查期为六个月。受此消息的影响，该公司股价大涨19.6%，至每股2.60美元。目前市值6.33亿美元。根据新闻稿，Lexicon表示，它已开始进行私募，预计将筹集约2.5亿美元。截至2023年底，公司将使用其中的一部分收入和其1.7亿美元现金支持药物商业化活动和研发，以及营运和其他一般公司用途。董事兼首席执行官Lonnel Coats说:“我们一直坚定地支持索格列净治疗1型糖尿病，并一直在努力确定一条监管途径，我们相信这将是一种重要的新疗法。”“我们现在将集中精力在年中之前重新提交我们的NDA，并争取尽早获得监管机构批准，用于许多患有CKD的1型糖尿病患者。”药物在美国的上市之路可谓是一路波折。2019年3月22日，Lexicon收到了FDA就索格列净治疗成人1型糖尿病新药上市申请发出的完整回复函(CRL)，指出该药物可能会增加糖尿病酮症酸中毒的风险。2019年7月，Lexicon当时的合伙人赛诺菲宣布与Lexicon终止项目合作，并于同年12月宣布退出糖尿病领域药物开发。2021年12月30日，公司又提交索格列净治疗成人2型糖尿病患者心力衰竭的新药上市申请。不过在2022年2月28日，Lexicon自愿撤回。2022年5月31日，Lexicon又重新提交了索格列净治疗心力衰竭的新药上市申请，并于2022年7月27日获得FDA受理。关于索格列净索格列净是一种口服SGLT-1/SGLT-2双效抑制剂。SGLT全称钠-葡萄糖协同转运蛋白，负责葡萄糖调控，有2种类型，SGLT-1主要负责胃肠道中葡萄糖的吸收，SGLT-2主要负责肾脏的葡萄糖重吸收。Sotagliflozin作用机制关于Lexicon Pharmaceuticals， Inc.Lexicon公司是一家致力于开发糖尿病领域治疗药物的公司，基于诺贝尔奖获奖技术，将独特的基因科学方法应用于发现和开发针对严重慢性病患者的精准药物。公司采用以患者为导向的方法，致力于发现和开发创新药物，以安全有效地治疗疾病并改善患者生活。公司管线参考资料:www.endpts.comwww.lexpharma.com

Lexicon Pharmaceuticals' original Zynquista FDA rejection was in 2019. Since then, the company has persisted in its regulatory efforts. Ever since its first FDA rejection five years ago, Lexicon Pharmaceuticals hasn’t given up hope on its Type 1 diabetes prospect sotagliflozin. Now, the company’s approval dreams could be coming into focus as the drugmaker prepares to refile its application. After hearing recent regulatory feedback from the agency, Lexicon said it plans to submit the drug by the middle of the year, the company said in a press release. “We have remained steadfast in our support of sotagliflozin in type 1 diabetes and have worked diligently to identify a regulatory path forward for what we believe will be an important new therapy,” CEO Lonnel Coats noted in the release. Lexicon is hoping for an approval that clears the drug to be used as an add-on to insulin therapy for adults with Type 1 diabetes mellitus and chronic kidney disease, the company said in its fourth-quarter and full-year earnings presentation (PDF). If approved, the drug will be branded as Zynquista. Lexicon hit the first bump on its regulatory road in 2019, when the FDA rejected its bid with a safety-related complete response letter following a 8-8 vote from an advisory committee. At the time, Sanofi was partnered on the drug, but the French pharma jumped ship after the rejection and subsequent trial flops in Type 2 diabetes. In the rejection, the FDA cited concerns about the risk of diabetic ketoacidosis for patients taking insulin plus Zynquista. However, Lexicon maintains that the risk can be managed and may be outweighed by patients' unmet needs. Despite the FDA rejection, Zynquista was approved in Europe in 2019. Lexicon has a trove of phase 3 data proving Zynquista’s worth in diabetes with chronic kidney disease when paired with insulin, the company has said. The long-awaited nod would be highly beneficial to Lexicon, which took home $1.2 million in total 2023 revenues. Net losses for the year came out to $175.6 million. At one point, some analysts had blockbuster-level expectations for the drug. Meanwhile, the drugmaker has been able to take sotaglifozin into another indication. The med scored approval for heart failure last year—branded as Inpefa—and launched weeks later, marking the first SGLT1/SGLT2 inhibitor to hit the U.S. market. The company is also testing the drug in hypertrophic cardiomyopathy.