A Phase 2 Double-blind Randomised Controlled Trial Studying the Effect of Sotagliflozin Versus Placebo in Individuals with Heart Failure and Type 1 Diabetes.

People with type 1 diabetes sometimes develop heart failure which can cause symptoms like breathlessness, tiredness or ankle swelling, reduced quality of life and lead to being admitted to hospital or suffering potential fatal consequences. This trial is investigating if a tablet called sotagliflozin, can improve quality of life in people with type 1 diabetes and heart failure. In addition, this trial will also assess the safety and tolerability of sotagliflozin in this population.
In previous trials that included people with type 2 diabetes and heart failure sotagliflozin was shown to improve patients' symptoms of heart failure, quality of life and reduce the chance of people with heart failure being admitted to hospital or dying. However, people with type 1 diabetes and heart failure were not included in these trials meaning that it is not known if these benefits also apply to this population.
This trial aims to recruit 320 people with type 1 diabetes and heart failure symptoms in multiple sites in the United Kingdom (UK). This trial will compare the health and quality of life of participants who take sotagliflozin tablets with participants who take placebo tablets, which is a dummy tablet that looks the same as sotagliflozin. Participants will be randomly allocated to one of two groups (i.e. one taking sotagliflozin and the other the placebo) and both the medical team and participants will not know in which group each participant is until the end of the study. Participants will be in the trial for approximately 6 months and will be given sotagliflozin or placebo tablets to take 1 per day for 4 months. The trial is expected to run for a total of 26 months.

开始日期2025-01-01

申办/合作机构

University Of Dundee

[+2]

NCT06510894 / Not yet recruitingN/AIIT

Diagnostic Utility of SGLT1/2 Inhibition to Facilitate Myocardial Glucose Suppression During Evaluation of Cardiac Inflammation on FDG-PET

This is a pilot mechanistic study of the diagnostic utility of sodium-glucose cotransporter-1/2 inhibition (SGLT1/2) on myocardial glucose suppression on FDG PET/CT. The investigators will test whether the addition of a SGLT1/2 inhibitor (SGLT1/2i) plus the standard dietary modification (ketogenic diet) will provide enhanced myocardial glucose suppression. The primary objective is to assess rates of complete myocardial glucose suppression (MGS) with 7 days of sotagliflozin 400 mg QD among healthy volunteers on a background of 1 day (N=20) or 3 days (N=20) of the KD. The secondary goal is to investigate the relationship between sotagliflozin, targeted metabolite levels, and myocardial glucose utilization on FDG-PET.
Participants will be asked to:
* undergo a screening visit that includes blood tests, vitals, and questions regarding health history/medications
* take the provided sotagliflozin as instructed for 7 days leading up to the scan
* follow a ketogenic diet as instructed for 1 or 3 days leading up to the scan
* undergo an FDG PET/CT scan, which includes vitals and blood draws

开始日期2024-11-01

申办/合作机构

University of Pennsylvania

[+1]

NCT06217302 / Not yet recruiting临床3期IIT

Effectiveness and Safety of Sotagliflozin in Slowing Kidney Function Decline in Persons With Type 1 Diabetes and Moderate to Severe Diabetic Kidney Disease

Powerful new drugs that can prevent or delay end stage kidney disease (ESKD) - so called sodium-glucose cotransporter-2 inhibitors (SGLT2i) - are now available for patients with type 2 diabetes. Whether these drugs have similar effects in patients with type 1 diabetes (T1D) remains unknown because of the few studies in this population, due to concerns about the increase in risk of diabetic ketoacidosis (DKA, a serious, potentially fatal acute complication of diabetes due to the accumulation of substances called ketone bodies) observed with SGLT2i therapy in T1D. One of the few T1D studies conducted to date showed that implementing an enhanced DKA prevention plan can reduce the risk of DKA associated with the SGLT2i sotagliflozin (SOTA) to very low levels. In the present study, a similar DKA prevention program will be used to carry-out a 3-year trial to test the kidney benefit of SOTA in 150 persons with T1D and moderate to advanced DKD. After a 2-month period, during which diabetes care will be standardized and education on monitoring and minimizing DKA implemented, eligible study subjects will be randomly assigned (50/50) to take one tablet of SOTA (200 mg) or a similarly looking inactive tablet (placebo) every day for 3 years followed by 2-months without treatment. Neither the participants nor the study staff will know whether a person was assigned to taking SOTA or the inactive tablet. Kidney function at the end of the study will be compared between the two treatment groups to see whether SOTA prevented kidney function loss in those treated with this drug as compared to those who took the inactive tablet. The DKA prevention program will include participant education, close follow-up with study staff, continuous glucose monitoring, and systematic ketone body self-monitoring with a meter provided by the study. If successful, this study will provide efficacy and safety data that could be used to seek FDA approval of SOTA for the prevention of kidney function decline in patients with T1D and DKD.

开始日期2024-10-15

申办/合作机构

Joslin Diabetes Center, Inc.

[+24]

100 项与索格列净相关的临床结果

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100 项与索格列净相关的转化医学

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100 项与索格列净相关的专利（医药）

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200

项与索格列净相关的文献（医药）

2024-09-01·Diabetes Technology & Therapeutics

Beta-Hydroxybutyrate Levels and Risk of Diabetic Ketoacidosis in Adults with Type 1 Diabetes Treated with Sotagliflozin

Article

作者: McGill, Janet B. ; Pettus, Jeremy ; Pratley, Richard ; Garg, Satish ; Boeder, Schafer ; Davies, Michael J. ; Girard, Manon ; Banks, Phillip

Introduction: Sodium glucose cotransporter inhibitors may increase beta-hydroxybutyrate (BHB) in insulin-requiring patients. We determined factors associated with BHB changes from baseline (ΔBHB) and diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) receiving sotagliflozin as an insulin adjunct. Research Design and Methods: This post hoc analysis compared ΔBHB levels in adults with T1D receiving sotagliflozin 400 mg or placebo for 6 months. We evaluated clinical and metabolic factors associated with ΔBHB and used logistic regression models to determine predictors associated with BHB values >0.6 and >1.5 mmol/L (inTandem3 population; N = 1402) or with DKA events in a pooled analysis (inTandem1-3; N = 2453). Results: From baseline (median, 0.13 mmol/L), median fasting BHB increased by 0.04 mmol/L (95% confidence interval, 0.03-0.05; P < 0.001) at 24 weeks with sotagliflozin versus placebo; 67% of patients had no or minimal changes in BHB over time. Factors associated with on-treatment BHB >0.6 or >1.5 mmol/L included baseline BHB and sotagliflozin use. Age, insulin pump use, sotagliflozin use, baseline BHB, and ΔBHB were significantly associated with DKA episodes. Independent of treatment, DKA risk increased by 18% with each 0.1-mmol/L increase in baseline BHB and by 8% with each 0.1-mmol/L increase from baseline. Conclusion: Incremental increases in baseline BHB and ΔBHB were associated with a higher DKA risk independent of treatment. Adding sotagliflozin to insulin increased median BHB over 24 weeks in patients with T1D and was associated with increased DKA events. These results highlight the importance of BHB testing and monitoring and individualizing patient education on DKA risk, mitigation, identification, and treatment.

2024-09-01·Neurobiology of Disease

Sotagliflozin attenuates cardiac dysfunction and depression-like behaviors in mice with myocardial infarction through the gut-heart-brain axis

Article

作者: Peng, Chendong ; Dai, Guangming ; Yang, Chengying ; Chang, Lijia ; Wei, Yan ; Feng, Ling ; Zhang, Lu ; Wang, Tong ; Liao, Lei ; Long, Yang ; Fan, Xinrong

Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001 were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.

2024-09-01·JACC: Heart Failure

Cost-Effectiveness of Sotagliflozin in SOLOIST-WHF

Article

作者: Zhang, Zugui ; Dolman, Sarahfaye ; Kolm, Paul ; Bhatt, Deepak L ; Weintraub, William S ; Alva, Maria

BACKGROUNDThe efficacy of sotagliflozin in patients with diabetes and recent worsening of heart failure was shown in the SOLOIST-WHF trial. However, the cost-effectiveness of sotagliflozin in these patients has not been previously investigated.OBJECTIVESThe authors sought to determine the cost-effectiveness of sotagliflozin in patients with diabetes and recent worsening of heart failure.METHODSBased on SOLOIST-WHF trial data (N = 1,222), the authors constructed a Markov model to estimate the lifetime impact of sotagliflozin from a U.S. health care sector perspective. Cost data were sourced from the National Inpatient Sample. Life expectancy was modeled from census data and modified by the mortality rate in SOLOIST-WHF. Fatal and nonfatal event rates were carried forward from the trial data. Utility was assessed from the published reports.RESULTSLifetime quality-adjusted life-years (QALYs) were 4.43 and 4.04 in the sotagliflozin and placebo groups, respectively, and lifetime costs were $220,113 and $188,198 in the sotagliflozin and placebo groups, respectively. The point estimate incremental cost-effectiveness ratio was $81,823 per QALY gained. The probability of being cost-effective was 3.6%, 67.5%, and 89.4% at willingness-to-pay thresholds of $50,000, $100,000, and $150,000, respectively, per QALY gained.CONCLUSIONSIn patients with diabetes and recent worsening of heart failure, sotagliflozin is cost-effective in the U.S. using commonly accepted willingness-to-pay thresholds. (Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure [SOLOIST-WHF]; NCT03521934).

164

项与索格列净相关的新闻（医药）

2024-11-16

·同写意

Lexicon：如果跌倒n次，那就爬起来第n+1次

此次医博会由同写意策划，以“发展新质生产力，共享健康新未来”为主题，用全新的视角瞄准国内外医药及大健康产业发展前沿。诚邀海内外医药及大健康各界嘉宾齐聚中国医药城，共赴时代之约。并不是所有的药物都能顺利进入市场，如果再得到FDA举“NO”的手牌，公司的命运又会遭受沉重一击。在这一方面，Lexicon Pharmaceuticals有话说。 Lexicon成立已近30年，旗下仅拥有一款去年获批的商业化产品Inpefa（sotagliflozin）。这家公司多次想要将1型糖尿病（T1D）的适应症收入囊中，但在FDA处屡战屡败，屡败屡战。 11月初，FDA委员会针对该产品用于T1D治疗的投票中再次给与负面态度。加州大学圣地亚哥分校的医学教授、“Taking Control Of Your Diabetes”创始人兼主任Steve Edelman支持这款产品，因为“患者需求很高，只有20%的T1D患者可靠胰岛素维持足够的血糖控制”。据估计，T1D患者群体的潜在市场高达4亿美元。其他一些预计中，sotagliflozin的销售额可能达到10亿美元。如果说在几年前的投票中，委员会的态度还算“暧昧”（票数为8-8），如今11-3的结果，让Lexicon通往T1D终点线的道路更加曲折。 1 3次打击 Sotagliflozin是一种双重抑制剂，同时靶向负责葡萄糖调节的两种钠葡萄糖协同转运蛋白SGLT1和SGLT2，通过抑制葡萄糖在肾脏和肠道的重吸收，助力糖尿病患者更好地控制血糖。今年6月，Lexicon提交sotagliflozin新适应症申请，作为胰岛素治疗的辅助药物，用于T1D和慢性肾脏病（CKD）患者的血糖控制。 11月初，FDA咨询委员会以“11-3”的票数，反对“sotagliflozin用于1型糖尿病合并CKD成年患者”，认为sotagliflozin的益处并不大于风险。 Lexicon新闻稿 Lexicon首席执行官兼董事Mike Exton表示，对咨询委员会的投票结果感到失望，“但我们受到了广泛的关注和讨论，支持将sotagliflozin提供给合适的T1D和CKD患者，这让我们感到振奋”。 FDA虽然还未给出最终审评结果（PDUFA的日期为2024年12月20日），但此前已经两次“打回”了sotagliflozin的新适应症申请。 2019年3月，Lexicon针对T1D递交sotagliflozin的上市申请，遭到FDA的拒绝，后者指出该药物可能会增加糖尿病酮症酸中毒的风险。随后的7月，赛诺菲宣布与Lexicon终止sotagliflozin的合作，并支付了2.6亿美元的“分手费”。两家公司在2015年达成授权协议，赛诺菲获得sotagliflozin除日本之外的全球独家权益，其中包括3亿美元的首付款，以及高达14亿美元的未来里程碑金额。 Lexicon对FDA的上述决定提出上诉，但FDA在2020年再次以安全问题为由拒绝。稍加欣慰的是，sotagliflozin治疗T1D适应症总是在FDA卡住，却以Zynquista的商品名在欧洲得以上市。 2019年4月，sotagliflozin获得EMA批准上市，作为胰岛素治疗的辅助药物，用于体重指数≥27kg/m2且接受胰岛素疗法仍无法达到足够血糖控制的T1D成人患者。Zynquista成为全球首款SGLT1/SGLT2双效口服降糖药。不过，sotagliflozin的欧洲之旅也不顺利。2022年，拥有Zynquista欧盟营销权的Guidehouse Germany出于商业原因，撤回了营销授权，目前该药品在欧盟已撤市。并不是Lexicon太背，而是SGLT1/2抑制剂治疗T1D本身让FDA有所顾虑。至今，仍未有一款SGLT1/2抑制剂获得FDA批准治疗T1D。同样获得过EMA批准治疗T1D、由阿斯利康推出的SGLT2抑制剂Farxiga，在2019年7月被FDA拒批相关适应症。 2020年3月，礼来宣布收到FDA的完全回复信，FDA拒绝批准其SGLT2抑制剂Jardiance用于治疗T1D的补充申请。Jardiance由礼来和勃林格殷格翰共同开发，于2014年8月获得FDA批准治疗2型糖尿病成人患者。 2 表现不佳的“唯一” Lexicon成立于1995年，曾用名为Lexicon Genetics，2000年在纳斯达克IPO。 “少年成名”往往伴着转折。成立已近30年的Lexicon，仅拥有一款商业化产品，也是上述产品sotagliflozin，在2023年5月获得FDA批准，用于降低患有心力衰竭，或患有2型糖尿病、慢性肾病，并携带其它心血管疾病风险因子成人患者的心血管死亡、因心力衰竭而住院或接受急救的风险，商品名为Inpefa。支持获批的III期临床试验（SOLOIST-WHF和SCORED）显示，与安慰剂相比，Inpefa显著降低患者因心力衰竭住院、因心力衰竭紧急就诊以及心血管死亡的复合风险达33%。值得一提的是，上述两项试验中入组对象都仅限于2型糖尿病患者，但FDA对sotagliflozin的批准范围未局限于糖尿病患者。可以看出，FDA充分认可该产品对心衰的作用。正如FDA对该产品的T1D适应症表现出同样坚定的“不认可”一样。今年5月，Lexicon公布了一项新的临床数据，分析显示，Inpefa能够降低包括射血分数保留型心力衰竭（HFpEF）患者在内的多样化患者群体中发生心力衰竭相关事件的风险。研究者指出，Inpefa在降低与肥胖相关的HFpEF患者发生心力衰竭相关事件风险方面尤其有效。根据华尔街分析师的预测，Inpefa在2024年销售额将增长超过1100%，达到4600万美元。大多数分析师预计，Inpefa的年销售额最终将超过5亿美元。但显然，Inpefa销售跟不上计划。根据财报，2024年第三季度，Inpefa销售额为170万美元。第二季度为160万美元，第一季度则是110万美元。未来可能会有一些上行空间。上个月，Lexicon与仿制药巨头Viatris签署了一项价值2500万美元的协议，获得Inpefa在美国和欧洲以外的销售权利，Lexicon保留了一些专利使用费。据路透社去年报道，Lexicon到2025年的预期销售额为1.12亿美元，2028年为5.76亿美元。又一个但是，Inpefa拥有一个非常强劲的竞争对手——来自勃林格殷格翰和礼来的Jardiance，已被批准用于降低2型糖尿病患者的心血管风险，以及心力衰竭和慢性肾脏疾病，这也是Lexicon正在寻求取得进展的适应症。勃林格殷格翰称，Jardiance取得了巨大成功，2023年的销售额达到80亿美元。这种药物的使用非常广泛，已被列入Medicare药品价格谈判计划的前10种药物，将于2026年生效。 3 更多机会在Lexicon执着的T1D适应症上，这家公司也披露了sotagliflozin的最新数据。新闻稿显示，近日在《美国肾脏病学会杂志》（JASN）的一篇研究论文，评估了sotagliflozin在T1D和CKD患者中与胰岛素联合使用的疗效和安全性。研究的结论是，接受Sotagliflozin和胰岛素治疗的T1D和CKD患者与无CKD的1型糖尿病患者相比，在降低糖化血红蛋白（HbA1c）方面具有相似的效果，这是试验的主要终点。此外，研究结果表明，sotagliflozin与较低至中性的严重低血糖风险相关，并且在少数DKA事件中未显著增加糖尿病酮症酸中毒的风险。 Lexicon新闻稿该研究的合著者、多伦多大学健康网络医学部肾脏科的专家David Cherney博表示：“之前的研究表明，包括sotagliflozin在内的SGLT抑制剂在降低T1D患者的血压和蛋白尿水平的程度与2型糖尿病患者相似。我们目前的分析补充了重要的证据，表明sotagliflozin有可能为T1D和CKD患者提供益处，特别是采取适当步骤降低糖尿病酮症酸中毒的风险后。” T1D之外，Lexicon正在进行sotagliflozin肥厚性心肌病适应症的III期试验，糖尿病周围神经性疼痛候选药物LX9211预计将于2025年第一季度披露IIb期的顶线数据。此外，Lexicon还拥有一款临床前肥胖药物。 Lexicon管线 Lexicon第三季度财报中还提及了用于肥胖和体重管理的ACSL5抑制剂LX9851，表示该产品有望在2025年中期提交IND。在对商业和管道项目进行战略审查后，Lexicon决定将推广工作重点放在心力衰竭适应症上，并且准备T1D和CKD的监管审批。作为重组计划的一部分，Lexicon在今年早些时候宣布将裁减大约一半的员工，以节省4000万美元的成本。据财报，Lexicon表示，由于Inpefa销售增加，公司2024年第三季度的收入为180万美元，2023年同期是20万美元。截至2024年9月30日，Lexicon拥有现金和投资2.584亿美元的，截至2023年12月31日为1.70亿美元。参考文章： 1、A diabetes drug, twice rejected, stumbles again — but its developer persists；pharmavoice 2、Lexicon新闻稿 3、“再战”1型糖尿病！索格列净于《美国肾病学会杂志》发表最新数据；凯莱英药闻同写意媒体矩阵，欢迎关注↓↓↓

引进/卖出

2024-11-14

·GlobeNewswire-Health Care

Post-Hoc Analysis Demonstrating Sotagliflozin Benefits Across Broad Spectrum of Heart Failure Patient Populations is Among Four Lexicon-Supported Presentations at the American Heart Association’s (AHA) Sessions 2024 in Chicago

Study results add to the growing body of evidence differentiating sotagliflozin within SGLT inhibitor classTHE WOODLANDS, Texas, Nov. 14, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that data from four studies of sotagliflozin will be delivered during the American Heart Association’s (AHA) Sessions 2024 being held November 16-18 at McCormick Place Convention Center in Chicago, Illinois. One of those studies, a secondary analysis of data from the Phase 3 SCORED clinical trial, examined the association of heart failure stage with cardiovascular disease and kidney events. Researchers in the study observed that sotagliflozin had similar relative benefits for all endpoints, irrespective of heart failure stage, with a corresponding increase in absolute benefits at earlier stages. Details of the four presentations are as follows: “Sotagliflozin, a Dual Inhibitor of Sodium-Glucose Transporters 1 and 2, Elicits Cardioprotective Effects Through Attenuation of Platelet Activation and Thrombosis,” -- a poster presentation, Saturday, November 16, 4:17-4:27p.m. CT, Poster# 4134384, South Level 1, Area S104B, presented by Livia Stanger, Ph.D. candidate, University of Michigan, Ann Arbor, Michigan "Effect of Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, on Systolic Blood Pressure in Patients with Type 2 Diabetes,” -- a poster presentation, Sunday, November 17. 11:30a.m.-12:30p.m., Poster# Su3019, Posters Zone 3, presented by M. Belinda Hardin, PharmD, US Medical Affairs, Lexicon Pharmaceuticals, Inc. “Association of the 2022 AHA/ACC/HFSA Heart Failure Staging and Cardiovascular and Kidney Outcomes in Patients with Diabetes and Kidney Disease: A Secondary Analysis of the SCORED Trial,” -- a moderated poster presentation, Sunday, November 17, 3:15-3:20p.m CT, Poster# MDP1133, Posters Zone 4, presented by Ayodele Odutayo, Ph.D., M.D., University of Toronto, Ontario “Sotagliflozin Reduces Contractile Work In Human Living Myocardial Slices,” -- a poster presentation, Sunday, November 17, 3:15-4:15p.m. CT, Poster# Su1070, Poster Zone 1, South Level 3, Science & Technology Hall, presented by Rebecca Taichman, M.D. candidate, University of Pennsylvania, Philadelphia, Pennsylvania “The post-hoc studies that will be presented at AHA reinforce our belief that sotagliflozin is differentiated within the SGLT inhibitor drug class. These studies help build a broad-based, scientific rationale supporting the dual mechanism of action of sotagliflozin,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. About SotagliflozinDiscovered using Lexicon’s unique approach to gene science, 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 and sodium reabsorption by the kidney and SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract. Sotagliflozin has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients. About Lexicon Pharmaceuticals Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through the Genome5000™ program, Lexicon’s unique genomics target discovery platform, 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 disease safely and effectively. Lexicon has commercially launched one of these medicines, INPEFA® (sotagliflozin) in the United States, and has a pipeline of other promising drug candidates in discovery and clinical and preclinical development in neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit www.lexpharma.com. Safe Harbor Statement This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, including the commercialization of its approved products and the clinical development of, regulatory filings for, and potential therapeutic and commercial potential of sotagliflozin and its other drug candidates. In addition, this press release also contains forward looking statements relating to Lexicon’s growth and future operating results, discovery, development and commercialization 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 its approved products, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of 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 approved products and other 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, 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. For Investor and Media Inquiries:Lisa DeFrancesco Lexicon Pharmaceuticals, Inc.lexinvest@lexpharma.com

临床3期AHA会议

2024-11-13

·凯莱英药闻

赛诺菲：联合投资2000万美元，获“首创”靶向SSTR2 1型糖尿病新药优先谈判权

欢迎关注凯莱英药闻 2024年11月12日，Zucara Therapeutics宣布，公司获得赛诺菲和PXV Fund I约2000 万美元的战略融资，作为该公司B轮融资的一部分。作为回报，赛诺菲获得ZT-01的独家优先谈判权。此次融资还将资助ZT-01正在进行的 2a 期试验的剩余部分，旨在评估 ZT-01 对1 型糖尿病（“T1D”）患者夜间低血糖事件的影响。关于ZT-01 ZT-01是一款生长抑素2型 (SSTR2)受体拮抗剂，能够预防使用胰岛素疗法的人发生低血糖。该药物每日一次，在1型糖尿病的治疗中具有潜在“同类首创”的作用机理。 1b 期概念验证试验显示：（1）近 90% 的受试者在服用 ZT-01 后胰高血糖素显著增加。（2）与安慰剂相比，采用3 mg和 20 mg ZT-01 ，分别导致峰值胰高血糖素相对于基线平均变化 14 pg/mL 和 20 pg/mL（p<0.0001）；16名受试者胰高血糖素比安慰剂增加了10 pg/mL以上。（3）研究未观察到严重的不良事件。临床前试验在腹膜内或皮下给药，以评估 ZT-01的药代动力学，显示：（1）腹腔给药后1小时内，ZT-01的血浆Cmax比早期的SSTR2抑制剂候选药物PRL-2903高10倍以上。（2）ZT-01经腹腔和皮下24小时暴露量分别为4.7倍和11.3倍。（3）在给药、PRL-2903或ZT-01后，达到超过3.0 mmol/L的低血糖的中位时间分别为60分钟、70分钟和125分钟。（4）注射ZT-01的大鼠在胰岛素给药后，血糖最低点明显高于PRL-2903。（5）在降糖钳夹期间，ZT-01比PRL-2903使胰高血糖素峰值反应提高了约4倍。关于SSTR2药物胰腺生长抑素 (SST)是一种多功能的多肽激素，由大脑、胃肠道、视网膜、免疫和神经内分泌细胞以及胰岛D细胞对不同的刺激产生。SST作为不同细胞功能的内源性抑制性调节因子，能调节发育、增殖、代谢、分泌和神经等过程，主要通过结合5种生长抑素受体(SSTR1-5)发挥广泛的生物效应。对于没有糖尿病的人来说，α 细胞会分泌胰高血糖素，向身体发出信号，释放自己的葡萄糖储备，以防止或逆转低血糖。然而，对于胰岛素依赖型糖尿病患者（包括患有 1 型糖尿病和胰岛素依赖型 2 型糖尿病的人），有证据表明，SST分泌增多会抑制 α 细胞释放胰高血糖素。目前，基于SSTR2靶点特性有多种药物开发形式：如核药、SSTR2激动剂、SSTR2拮抗剂、多肽偶联药物等，适应症涵盖肿瘤、罕见疾病、内分泌及代谢领域。关于1型糖尿病糖尿病是危害人类健康最常见的慢性疾病之一，我国已经成为全球糖尿病患病人数增长最快的国家，18岁以上人群糖尿病患病率超过10%。近年来，糖尿病发病年轻化也是不容小窥的公共卫生问题。根据2019年世界卫生组织（WHO）最新的糖尿病分型标准，糖尿病分为1型糖尿病、2型糖尿病、妊娠糖尿病、混合型糖尿病、未分类型糖尿病、特殊类型糖尿病。 1型糖尿病的病人是由于免疫系统的破坏导致的，主要是免疫系统对胰岛β细胞的破坏，造成绝大部分的胰岛β细胞受到严重的损害，导致胰岛β细胞死亡。残留的胰岛β细胞比较少，产生的胰岛素，不能满足身体的需要，造成血糖的升高。据推测，全球可能有230万人患有1型糖尿病。根据翁建平教授等人在2010~2013年调查发现，中国所有年龄段的T1DM发病率估计为1.01/10万人年。除了每天注射胰岛素外，T1D患者还需要采取严格的管理计划，包括定期监测血糖、健康饮食和体育锻炼。关于赛诺菲在糖尿病领域的布局赛诺菲在全球糖尿病市场都占据着领先地位，布局了多款小分子降糖药和胰岛素、多肽药物；其中，代表药物甘精胰岛素利司那肽同时含有基础胰岛素与GLP-1 RA双重组分，一天一针就能有效控制患者的空腹血糖和餐后血糖，有效减少了注射次数，控糖简便且全面。在1型糖尿病领域，早在2015年，赛诺菲曾与Lexicon达成17亿美元的授权协议，获得索格列净除日本之外的全球独家权利。然而在2019年7月，赛诺菲宣布与Lexicon终止合作，理由是在治疗伴有中度（3期）和重度（4期）慢性肾脏病（CKD）的2型糖尿病患者中开展的2项III期研究（SOTA-CKD3、SOTA-CKD4）中，数据没有达到赛诺菲的预期目标。 2023年3月，赛诺菲以每股25.00美元现金，股权价值约为 29 亿美元收购Provention Bio，将包含替利珠单抗在内多款自免药物收入囊中。替利珠单抗（teplizumab）是第一种可预防/延缓特定人群发展为临床T1D（3 期T1D）的疗法，是继一个世纪前胰岛素问世以来，T1D治疗方面取得的第一个重大进展。2022年11月，替利珠单抗（商品名：Tzield）获FDA批准延迟2 期T1D成人患者和8 岁及以上儿童患者的3期T1D的发病。2024年8月，替利珠单抗注射液的上市申请获CDE受理并纳入优先审评，用于成人和8岁及以上儿童1型糖尿病2期患者，以延缓3期T1D发病，有望成为我国首个1型糖尿病延缓发病治疗药物。公司在糖尿病领域布局的临床阶段药物感谢关注、转发，转载授权、加行业交流群，请加管理员微信号“hxsjjf1618”。 “在看”点一下

临床2期临床结果

100 项与索格列净相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10669	索格列净	A10BK06	DB12713

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
心脏衰竭	美国	Lexicon Pharmaceuticals, Inc.	2023-05-26

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
1型糖尿病	临床2期	列支敦士登	NCI Healthcare LLC	2019-04-26
1型糖尿病	临床2期	挪威	NCI Healthcare LLC	2019-04-26
1型糖尿病	临床2期	冰岛	NCI Healthcare LLC	2019-04-26

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


Pubmed 人工标引	N/A	1型糖尿病 \| 慢性肾病	-	Sotagliflozin 200mg (CKD)	(鏇構餘衊顧選網餘鹽壓) = 鹹構膚築餘衊齋獵網齋鹽鑰範壓淵顧蓋襯鏇網 (繭糧壓築壓襯餘餘願鹽 ) 更多	积极	2024-11-01
				Sotagliflozin 400mg (CKD)	(鏇構餘衊顧選網餘鹽壓) = 餘顧淵淵範窪鹹遞製鹹鹽鑰範壓淵顧蓋襯鏇網 (繭糧壓築壓襯餘餘願鹽 ) 更多
NCT03285594 (SOTA-INS, GlobeNewswire) 人工标引	临床3期	2型糖尿病	-	Sotagliflozin 400 mg	(繭製糧醖艱衊夢夢壓構) = 膚鏇齋蓋觸膚簾衊襯鬱選蓋願鏇衊壓積襯網餘 (艱鹹蓋膚鏇襯膚糧製觸 )	积极	2024-09-10
				Sotagliflozin 200 mg	(繭製糧醖艱衊夢夢壓構) = 壓憲壓憲獵衊廠願繭遞選蓋願鏇衊壓積襯網餘 (艱鹹蓋膚鏇襯膚糧製觸 )
NCT03521934 (SOLOIST-WHF, Pubmed \| J Am Coll Cardiol)	临床3期	2型糖尿病 \| 心脏衰竭	-	Sotagliflozin	醖鹽餘醖積簾衊製鑰壓(壓夢衊衊鹽餘鏇範遞衊) = The baseline KCCQ-12 score was low overall (median: 41.7; Q1-Q3: 27.1-58.3) and improved by 4 months in both groups 範夢選製選願憲獵糧鬱 (繭壓製簾願醖壓壓鑰蓋 )	积极	2024-09-01
				Placebo
ESC2024	N/A	糖尿病	-	Sotagliflozin	獵鬱願積選窪醖繭醖顧(選餘衊鬱顧願鹹繭襯膚) = 遞簾淵醖夢鹽鹽糧齋窪簾構齋鏇醖醖憲繭膚構 (繭願淵製艱夢齋築顧夢 ) 更多	-	2024-08-30
				Placebo	獵鬱願積選窪醖繭醖顧(選餘衊鬱顧願鹹繭襯膚) = 製願構膚鹹襯鑰構夢鬱簾構齋鏇醖醖憲繭膚構 (繭願淵製艱夢齋築顧夢 ) 更多
917-P (ADA2024)	临床3期	-	770	Sotagliflozin 400 mg	夢鏇製範艱築鬱範鬱鬱(蓋艱獵餘窪廠簾網憲壓) = Other adverse events in the SOTA group aligned with expectations associated with SGLTi therapy 襯獵艱簾繭衊構選膚壓 (糧鏇觸鏇膚衊獵膚獵觸 ) 更多	积极	2024-06-14
				Empagliflozin 25 mg
924-P (ADA2024)	临床3期	2型糖尿病追加	570	Sotagliflozin 400 mg	鏇艱鬱遞襯選鑰鏇膚膚(鑰積製顧餘夢願糧鬱膚) = 壓窪襯餘遞觸憲構憲顧鏇範範範遞製衊襯鬱膚 (壓鬱範顧衊蓋醖鏇廠齋 )	积极	2024-06-14
				Sotagliflozin 200 mg	鏇艱鬱遞襯選鑰鏇膚膚(鑰積製顧餘夢願糧鬱膚) = 齋糧衊顧壓夢觸獵顧獵鏇範範範遞製衊襯鬱膚 (壓鬱範顧衊蓋醖鏇廠齋 )
SCORED (GlobeNewswire) 人工标引	临床3期	心脏衰竭	1,932	INPEFA® (sotagliflozin)	(衊壓膚醖鬱簾獵夢鬱艱) = 獵鹽繭鏇顧衊淵齋糧廠網蓋願壓構餘鹽顧蓋齋 (網願鏇願願淵鏇網構構 )	积极	2024-05-14
SOLOIST-WHF and SCORED (ESC2024)	N/A	obesity \| type 2 diabetes (T2D)	-	Sotagliflozin	蓋選襯壓鏇壓遞構窪構(壓鏇膚艱願遞夢願觸壓) = 憲鹽窪艱構願衊鹽願膚衊窪糧鹹壓淵蓋憲襯簾 (襯醖鹹製獵簾齋艱衊願 )	积极	2024-05-14
NCT03315143 (SCORED, ACC2024) 人工标引	临床3期	心血管疾病 \| 2型糖尿病 \| 慢性肾病	10,584	Sotagliflozin	(蓋範夢糧構網襯鏇窪醖) = 窪衊築選繭觸窪簾夢選鏇醖淵糧鑰鬱艱膚膚構 (簾窪網窪鏇蓋憲壓窪鬱 ) 更多	积极	2024-03-25
				Placebo	(蓋範夢糧構網襯鏇窪醖) = 蓋製繭艱膚觸鹹製憲遞鏇醖淵糧鑰鬱艱膚膚構 (簾窪網窪鏇蓋憲壓窪鬱 ) 更多
SCORED (GlobeNewswire) 人工标引	N/A	心脏衰竭	-	INPEFA	(窪鬱顧糧鬱獵簾選鬱壓) = 積衊齋範醖製壓襯獵艱襯鹹築選願選蓋蓋網夢 (鏇鹹膚齋構築壓壓廠簾 ) 更多	积极	2023-11-12
				placebo	-