Clinical Data on the Impact of Sotagliflozin on Stroke and Heart Attack Risk Among Four Lexicon-Sponsored Presentations at the American College of Cardiology 73rd Annual Scientific Session & Expo
Clinical Data on the Impact of Sotagliflozin on Stroke and Heart Attack Risk Among Four Lexicon-Sponsored Presentations at the American College of Cardiology 73rd Annual Scientific Session & Expo
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.
得克萨斯州伍德兰兹，2024年3月25日（GLOBE NEWSWIRE）——Lexicon Pharmicals, Inc.（纳斯达克股票代码：LXRX）今天宣布，与两种钠葡萄糖转运蛋白（SGLT2 和 SGLT1）的抑制剂索他列嗪相关的四份数据报告将在2024年4月6日至8日在佐治亚州亚特兰大举行的美国心脏病学会第73届年度科学会议和博览会期间发布，其中包括来自以下方面的结果事后评估索他列津在减少 2 型糖尿病、慢性肾脏病 (CKD) 和高血压患者中风事件方面的功效SCORED 3期临床试验中的心血管（CV）风险。
"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.
Lexicon高级副总裁兼首席医学官克雷格·格拉诺维茨医学博士说：“继美国食品药品管理局于2023年批准INPEFA（索塔格列津）治疗心力衰竭（HF）之后，研究人员增加了对索他列津的总体科学理解，包括其能够降低中风和心肌梗塞（MI）或心脏病发作风险的临床证据。”
Details of the presentations are as follows:
演讲详情如下：
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 York
Study 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降低了糖尿病和慢性肾脏病患者的中风预后——由主持的海报发布会，美国东部时间4月8日星期一下午12点15分至12点25分，8号剧院，由纽约西奈山伊坎医学院医学博士拉胡尔·阿格瓦尔主持
研究人员评估了索他格列津在降低2型糖尿病、慢性肺病和高心血管风险患者全因和特定病因中风预后方面的功效。在对SCORED三期临床试验中10,584名患者的数据进行的事后分析中，发生了213起全因中风事件，包括29起（13.6％）致命事件。Sotagliflozin将全因中风的风险降低了34％，在sotagliflozin组中，每100名患者年中有1.2起事件，在安慰剂组中，每100名患者年中有1.8起事件。同样，sotagliflozin将缺血性中风的风险降低了32％，在sotagliflozin组中，每100名患者年中有0.8起事件，在安慰剂组中，每100名患者年中有1.2起事件。
点击此处查看在线摘要中的更多研究详情。
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, Massachusetts
Study 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是一种双重SGLT 1和2抑制剂，可调节血管紧张素II刺激后内皮细胞中葡萄糖转运和炎症蛋白的表达 — 海报展示，美国东部时间4月7日星期日下午 1:15 — 2:00，1425-157，B4-5厅，由马萨诸塞州贝弗利Elucida Research工商管理硕士普雷斯顿·梅森主持
研究人员发现，Sotagliflozin调节了与体外炎症刺激下的人体内皮细胞中与Akt信号通路、葡萄糖转运和血管舒张相关的蛋白质的表达。sotagliflozin在炎症期间的良好内皮细胞作用增加了人们对sotagliflozin作用机制的了解，并且与结果试验中显示的降低动脉粥样硬化风险相一致。
点击此处查看在线摘要中的更多研究详情。
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, Michigan
Study 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.
Sotagliflozin是同类首创的SGLT1/2抑制剂，它通过抑制人血小板激活、整合素激活和聚集来抑制血管中的凝血潜力——由美国东部时间4月7日星期日上午11点30分至2点40分主持的海报发布会，由密歇根大学密歇根大学安娜堡分校博士候选人利维亚·斯坦格主持
研究人员发现，索他格列津通过同时靶向 SGLT1 和 SGLT2 来抑制血小板活化。这些发现使人们深入了解索塔格列津影响2型糖尿病和慢性肾病患者中风和心肌梗死风险的潜在机制，并为进一步研究探索索他格列津在缺血事件风险较高的患者心血管保护中的作用提供了基础。
点击此处访问在线摘要中的研究详情。
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, Colorado
Study 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.
根据性别和年龄向住院患者开的心力衰竭药物的时间变化。美国两个大型综合卫生系统的结果——海报展示，美国东部时间4月7日星期日上午9点15分至10点，1343-121，B4-5展厅，由科罗拉多大学奥罗拉多大学CPC临床研究博士Mario Enrico Canonico主持
研究人员发现，存在进一步改善HF患者指南导向药物治疗（GDMT）处方的巨大机会。按性别和年龄划分的开始这些疗法的时间差异凸显了根据这些和其他健康决定因素来评估护理差距的必要性。
点击此处查看在线摘要中的更多研究详情。
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:
2023年5月26日，美国食品药品监督管理局批准了INPEFA（sotagliflozin），这是一种每日一次的口服片剂，用于降低患有以下情况的成年人心血管死亡、心力衰竭住院和紧急心力衰竭就诊的风险：
heart failure or
type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors.
心力衰竭或
2 型糖尿病、慢性肾脏病和其他心血管危险因素。
About Lexicon Pharmaceuticals
关于 Lexicon 制药
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 .
Lexicon 是一家生物制药公司，其使命是开创改变患者生活的药物。通过其Genome5000计划，Lexicon科学家研究了近5,000个基因的作用和功能，并确定了100多个在一系列疾病中具有巨大治疗潜力的蛋白质靶标。通过精确靶向这些蛋白，Lexicon开创了安全有效地治疗疾病的创新药物的发现和开发。Lexicon已将多种药物推向市场，并在心力衰竭、神经性疼痛、糖尿病和新陈代谢及其他适应症方面有一系列前景看好的候选药物。如需更多信息，请访问。
About INPEFA (sotagliflozin)
关于 INPEFA（索塔格列津）
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.
INPEFA（sotagliflozin）是使用Lexicon独特的基因科学方法发现的，是两种负责葡萄糖调节的蛋白质的口服抑制剂，即2型和1型钠-葡萄糖协同转运蛋白（SGLT2 和 SGLT1）。SGLT2 负责肾脏重吸收葡萄糖，SGLT1 负责胃肠道中的葡萄糖吸收。INPEFA已在涉及约20,000名患者的临床研究中对包括心力衰竭、糖尿病和慢性肾脏病在内的多个患者群体进行了研究。
INDICATION
指示
INPEFA is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with:
INPEFA可降低患有以下情况的成年人心血管死亡、心力衰竭住院和紧急心力衰竭就诊的风险：
heart failure or
type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors
心力衰竭或
2 型糖尿病、慢性肾脏病和其他心血管危险因素
IMPORTANT SAFETY INFORMATION
重要的安全信息
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.
剂量：评估肾功能和容量状态，如有必要，在开始使用INPEFA之前纠正血容量消耗。失代偿性心力衰竭患者的INPEFA剂量可以在患者血流动力学稳定时开始，包括住院时或出院后立即给药。
Contraindications: INPEFA is contraindicated in patients with hypersensitivity to any component.
禁忌症：INPEFA禁用于对任何成分过敏的患者。
Warnings and Precautions:
警告和注意事项：
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.
酮症酸中毒：INPEFA会增加1型糖尿病（T1DM）患者发生酮症酸中毒的风险。2 型糖尿病 (T2DM) 和胰腺疾病也是危险因素。剂量越高，酮症酸中毒的风险可能会更大。有上市后报道称，使用钠葡萄糖转运蛋白 2 (SGLT2) 抑制剂的 2 型糖尿病患者会出现酮症酸中毒的致命事件。在启动INPEFA之前，评估酮症酸中毒的危险因素。考虑对T1DM患者进行酮体监测，考虑对其他有酮症酸中毒风险的患者进行酮监测，并教育患者了解酮症酸中毒的体征/症状。在已知易患酮症酸中毒的临床情况下，接受INPEFA的患者可能需要监测并暂时停止治疗。
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.
评估出现代谢性酸中毒或酮症酸中毒体征和症状的患者，无论血糖水平如何。如果怀疑，请立即停用 INPEFA，进行评估并进行治疗。在重启INPEFA之前，监测患者酮症酸中毒的缓解情况。
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.
血容量不足：INPEFA 可导致血管内容量不足，有时可能表现为症状性低血压或肌酐急性短暂变化。已有上市后报道，接受 SGLT2 抑制剂的 2 型糖尿病患者出现急性肾损伤，有些需要住院和透析。肾功能受损患者（eGFR
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.
尿毒症和肾盂肾炎：使用包括 INPEFA 在内的 SGLT2 抑制剂进行治疗会增加尿路感染的风险。已报告了严重的尿路感染，包括尿脓毒症和肾盂肾炎，需要住院治疗。评估患者是否有尿路感染的体征和症状，并及时治疗。
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.
与胰岛素和胰岛素促分泌剂同时使用会导致低血糖：已知胰岛素和胰岛素促分泌剂会导致低血糖。INPEFA与胰岛素或胰岛素促分泌剂合用可能会增加发生低血糖的风险。因此，与INPEFA一起使用时，可能需要较低剂量的胰岛素或胰岛素促分泌剂，以最大限度地降低低血糖的风险。
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.
会阴坏死性筋膜炎（富尼尔坏疽）：在对接受 SGLT2 抑制剂的糖尿病患者的上市后监测中，已发现富尼尔坏疽是一种罕见但严重且危及生命的坏死性感染，需要紧急手术干预。评估生殖器或会阴部位出现疼痛、压痛、红斑或肿胀以及发烧或全身不适的患者。如果怀疑，立即开始使用广谱抗生素治疗，必要时进行手术清创治疗。停用INPEFA，密切监测患者的体征和症状，并为心力衰竭提供适当的替代疗法。
Genital Mycotic Infections: INPEFA increases the risk of genital mycotic infections. Monitor and treat as appropriate.
生殖器真菌感染：INPEFA增加了生殖器真菌感染的风险。进行适当的监测和治疗。
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.
尿糖测试和 1,5-脱氢葡萄糖醇 (1,5-AG) 检测：对于服用 SGLT2 抑制剂的患者来说，这些测试并不可靠。使用其他测试方法监测血糖水平。
Common Adverse Reactions: the most commonly reported adverse reactions (incidence ≥ 5%) were urinary tract infection, volume depletion, diarrhea, and hypoglycemia.
常见不良反应：最常报告的不良反应（发生率 ≥ 5%）是尿路感染、容量不足、腹泻和低血糖。
Drug Interactions:
药物相互作用：
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.
地高辛：适当监测患者，因为与INPEFA 400 mg联合使用时，地高辛的暴露量会增加。
尿苷5'-二磷酸葡萄糖醛酸转移酶（UGT）诱导剂：利福平（UGT）诱导剂，与索他格列嗪共同给药可减少索他列嗪的暴露量。
锂：将 SGLT2 抑制剂与锂同时使用可能会降低血清锂浓度。在INPEFA启动期间和剂量变化期间，更频繁地监测血清锂浓度。
Use in Specific Populations:
在特定人群中使用：
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.
怀孕和哺乳：不建议在怀孕的第二和第三个月以及哺乳期间使用 INPEFA。
老年用途：不建议根据年龄改变INPEFA剂量。未发现这些患者与年轻患者之间疗效的总体差异，其他报告的临床经验也没有发现老年患者和年轻患者之间的反应差异，但不能排除一些老年人更敏感的可能性。老年患者发生容量消耗不良反应（包括低血压）的风险可能增加。
肾功能受损：INPEFA对慢性肾脏病患者（表皮生长因子25至60 mL/min/1.73 m2）和表皮生长因子
肝功能受损：不建议中度或重度肝损伤患者使用INPEFA。