A Phase 1, Multi-center, Open-label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Multiple Oral Doses (6 Days) of 100 mg Resmetirom in Subjects With Severe Renal Impairment and in Matched Healthy Control Subjects With Normal Renal Function

The purpose of this study is to directly characterize the pharmacokinetic (PK) profiles of resmetirom and its major metabolite (MGL-3623) following oral administration of 100 mg resmetirom (QD x 6 days) in subjects with severe renal impairment (RI) compared to healthy matched control subjects with normal renal function.

开始日期2024-03-05

申办/合作机构

Madrigal Pharmaceuticals, Inc.

NCT05500222 / Recruiting临床3期

A Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Effect of Resmetirom on Liver-related Outcomes in Patients With Well-compensated (Child-Pugh A) Non-alcoholic Steatohepatitis (NASH) Cirrhosis (MAESTRO-NASH-OUTCOMES)

This study will determine the effect of oral 80 mg resmetirom administered once daily on participants with well-compensated non-alcoholic steatohepatitis (NASH) cirrhosis by measuring the time to experiencing a Composite Clinical Outcome event.

开始日期2022-08-26

申办/合作机构

Madrigal Pharmaceuticals, Inc.

NCT04951219 / Recruiting临床3期

A 52-Week, Phase 3, Open-Label Extension Study, With a Double-blind Lead-in, to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)

A 52-Week, Multi-center, Open-label, Active Treatment Extension Study to Evaluate Safety and Tolerability of Once Daily, Oral Administration of Resmetirom (MGL-3196)

开始日期2021-07-09

申办/合作机构

Madrigal Pharmaceuticals, Inc.

100 项与 Madrigal Pharmaceuticals, Inc. 相关的临床结果

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0 项与 Madrigal Pharmaceuticals, Inc. 相关的专利（医药）

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项与 Madrigal Pharmaceuticals, Inc. 相关的文献（医药）

2024-12-31·JOURNAL OF MEDICAL ECONOMICS

Budget impact of resmetirom for the treatment of adults with non-cirrhotic non-alcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis)

Article

作者: Parise, Helene ; Smith, Zachary ; Parisé, Hélène ; Bercaw, Eric ; Kim, Yestle ; Fishman, Jesse

AIMS:

This study assessed the budget impact of resmetirom as a treatment for adults with non-cirrhotic non-alcoholic steatohepatitis (NASH) with moderate-to-advanced liver fibrosis and estimated total costs for a hypothetical private payer in the United States.

MATERIALS AND METHODS:

A three-year budget impact analysis based on an open cohort state transition model was developed for a hypothetical one-million-member private health plan. The comparator was Standard of Care (SOC), defined as routine care for non-cirrhotic NASH patients with moderate-to-advanced liver fibrosis. Each year, the number of resmetirom treatment-eligible patients was estimated through prevalent, incident, and diagnostic rate estimates. Costs included resources incurred by the medical and pharmacy benefits of private payers, including resmetirom drug acquisition costs, diagnosis and monitoring, other medical and other prescription costs stratified by disease progression status (i.e., non-cirrhotic vs. cirrhotic/advanced liver diseases). Resmetirom adverse event management costs were included in sensitivity analysis. Drug costs were estimated based on the average wholesale acquisition cost as of March 2024. Other costs were based on published sources and inflated to 2023 US dollars. Budget impact outcomes were presented in aggregate, net, and on a per-member per-month (PMPM) basis.

RESULTS:

Compared with a scenario without resmetirom, the introduction of resmetirom yielded results ranging from 50 to 238 treated patients, net budget impact of $2.2 to $9.5 million, and PMPM from $0.19 to $0.80 over years one and three. Net costs excluding resmetirom declined over time. In sensitivity analyses, results were most sensitive to diagnostic and epidemiologic inputs.

LIMITATIONS:

Market shares are based on internal forecasts, a short time horizon, average treatment effects, and other limitations common to BIMs.

CONCLUSION:

The adoption of resmetirom on the formulary for the treatment of non-cirrhotic NASH with moderate-to-advanced liver fibrosis resulted in a moderate increase in budget impact with declining costs related to NASH progression.

2024-11-01·ADVANCES IN THERAPY

Progression from Non-alcoholic Steatohepatitis to Advanced Liver Diseases and Mortality Among Medicare Patients

Article

作者: Nunag, Dominic ; Gish, Robert ; Medicis, Joe ; Davis, Matthew ; Kim, Yestle

INTRODUCTION:

Non-alcoholic steatohepatitis (NASH) may progress to more advanced liver disease. This study aimed to characterize NASH progression and mortality in the Medicare population.

METHODS:

Patients with NASH in 100% Medicare fee-for-service claims accrued from 2015-2021 who were ≥ 66 years old at index diagnosis, continuously enrolled for ≥ 12 months prior to and ≥ 6 months following index (unless death), and had no evidence of other causes of liver disease were included. Diagnosis codes defined severity states: non-cirrhotic NASH, compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), and liver transplant (LT). Survival analyses of disease progression and mortality were conducted for each state and by year of progression (Y1-5). Cox proportional hazards models assessed risk factors of worsening disease.

RESULTS:

Mean age and follow-up were 72.2 and 2.8 years in 14,806 unique patients (n = 12,990 NASH; 1899 CC; 997 DCC; 209 HCC; 140 LT). Progression rates were highest for patients with CC (11-37% for Y1-5), followed by DCC (3-18%), NASH (3-12%), and HCC (2-4%). Mortality rates were highest for patients with HCC (41-85% for Y1-5), followed by DCC (41-76%), LT (7-33%), CC (6-26%), and NASH (2-12%). Patients with any disease progression had a 5-year mortality rate more than double that of patients without progression (41% vs. 16%). Delayed progression from NASH was associated with lower mortality risk; the 5-year mortality rate was 26% lower for patients with progression in Y2 vs. Y1 (32% vs. 43%) and further decreased for progression in Y3-Y5. Risk factors included age, nursing home use, congestive heart failure, coagulopathy, fluid/electrolyte disorders, and unexplained weight loss.

CONCLUSION:

Medicare patients ≥ 66 years with NASH experience high risk of disease progression associated with increased mortality rates. Slower disease progression is associated with lower mortality rates, suggesting that therapies that can delay or prevent NASH progression may reduce morbidity and mortality.

2024-11-01·ADVANCES IN THERAPY

Estimation of the Eligible Population For Resmetirom Among Adults in the United States for Treatment of Non-Cirrhotic NASH with Moderate-to-Advanced Liver Fibrosis

Article

作者: Smith, Zachary J ; Bercaw, Eric M ; O'Connell, Tom ; Kim, Yestle ; Fishman, Jesse ; Charlton, Michael R

INTRODUCTION:

As of March 2024, resmetirom is the first and only therapy approved in the United States (US) for the treatment of adults with non-cirrhotic nonalcoholic steatohepatitis (NASH) with moderate-to-advanced liver fibrosis (MALF) consistent with stages F2/F3 fibrosis. Estimates of the diagnosed, treatment-eligible NASH population are poorly understood due to diagnostic variability. This study provides a contemporary estimate of the size of the US resmetirom treatment-eligible population.

METHODS:

A dynamic population calculator was developed combining literature, screening guidelines, resmetirom study criteria, and analyses of the NHANES 2017-March 2020 cycle. It computes NASH prevalence, proportion non-cirrhotic NASH with MALF, Year 1 diagnosis, and new diagnoses in Years 2 and 3. NASH prevalence was estimated by applying the American Association of Clinical Endocrinology screening algorithm and recommended NIT cut-offs in the NHANES dataset. The proportion of non-cirrhotic NASH with MALF was informed by analyses of the Forian US integrated medical claims database using NASH and cirrhosis-specific ICD-10-CM codes and FIB-4 scores. NASH diagnosis rates were obtained from published estimates and NHANES responses. Treatment-eligible population growth was projected using published incidence data. Estimates were compared to a NASH budget-impact-analysis (BIA) from the Institute for Clinical and Economic Review (ICER).

RESULTS:

In the base case, a NASH prevalence of 4.6% was modeled (range 1.3-14.2%). This value was multiplied by the proportion estimated to have non-cirrhotic MALF (i.e., 35%). Published analyses suggest a diagnosis rate of ~ 10% (range 3.3-14.3%) and ~ 16% year-over-year growth in the treatment-eligible population. Assuming a 1-million commercial-member population, the resmetirom treatment-eligible population was estimated as 1255-1699 in Years 1-3 following approval. Sensitivity analyses were conducted and comparison to the ICER BIA was influenced by different diagnosis rates.

CONCLUSION:

Estimation of the treatment-eligible population for resmetirom depends importantly on NASH diagnosis rates, which are predicted to be < 15% in the 3 years after drug approval. Nonalcoholic steatohepatitis (NASH) is an advanced form of nonalcoholic fatty liver disease. Previously there were no treatments for NASH in the United States (US), but as of March 2024, the US Food and Drug Administration (FDA) approved resmetirom (REZDIFFRA™), a once-daily, oral therapy, in conjunction with diet and exercise, under accelerated approval for the treatment of adults (aged 18 years or older) with non-cirrhotic NASH with moderate-to-advanced liver fibrosis (MALF), consistent with stages F2-F3. It is not well understood how many diagnosed patients with NASH would be eligible for treatment with resmetirom; thus, this study aimed to estimate the size of the US resmetirom treatment-eligible population. To do so, we created a flexible population calculator that considers how many people have NASH, what proportion would be eligible for resmetirom treatment-i.e., have non-cirrhotic NASH with MALF-and of those how many people would be diagnosed. We used published literature, screening guidelines, resmetirom study criteria, and analyses of national surveys to inform our range of estimates. In the main analysis, we modeled a NASH prevalence of 4.6% (range 1.3-14.2%), which was then limited to the proportion estimated to have non-cirrhotic NASH with MALF (i.e., 35%) and diagnosed (i.e., 10%, range 3.3-14.3%). A year-over-year growth of approximately 16% in the treatment-eligible population was modeled in years following approval. Assuming a population of 1 million commercial insurance enrollees, the resmetirom treatment-eligible population was estimated to be 1255-1699 in Years 1-3 following approval. We assessed alternative scenarios and have compared our results to existing models.

483

项与 Madrigal Pharmaceuticals, Inc. 相关的新闻（医药）

2024-11-04

·PRNewswire

Echosens Launches its Liver Health Management (LHM) Platform Globally, Streamlining Liver Care

The cloud-based platform enhances FibroScan® capabilities, providing advanced tools for data-driven liver disease management PARIS, Nov. 4, 2024 /PRNewswire/ -- Liver disease affects an estimated 1.5 billion people worldwide, with many cases going undiagnosed until it's too late. As liver conditions like metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) become more common, the need for early detection and proactive management has never been more urgent. To address this global health crisis, Echosens has launched its Liver Health Management (LHM) platform—a cloud-based solution designed to streamline liver disease care for healthcare providers in diverse clinical environments. The LHM platform integrates seamlessly with Echosens' FibroScan® technology, offering automated result transfers, biological marker-enhanced exams, and interpretation tools that support more informed, data-driven decision-making. "The LHM platform is designed to meet the growing needs of healthcare providers who are seeing an increase in patients with liver disease," said Dominique Legros, Group CEO of Echosens. "By connecting FibroScan® with the LHM platform, providers can access real-time insights and deliver more precise, data-driven care. The platform unlocks next-level liver disease management, enhancing efficiency and empowering clinicians to streamline workflows, improve patient outcomes, and stay ahead of the rising demand for liver care." Key features of the LHM platform, including worklist synchronization between FibroScan® devices and the platform, remote results interpretation, and secure data storage, allow providers to easily integrate liver care into their clinical workflows. This ensures efficient management of patient data while delivering comprehensive liver assessments. "The LHM platform is transforming our ability to monitor and manage liver disease," said gastroenterologist, Dr. Angelo Paredes. "With automated FibroScan® result transfers and intuitive interpretation tools, we can quickly identify at-risk patients and make informed decisions, allowing us to deliver timely recommendations and interventions to improve patient outcomes." Liver disease often progresses silently, with symptoms appearing only in advanced stages. With one in four people affected by MASLD and many undiagnosed, the LHM platform provides a critical solution by making liver screening routine, accessible, and actionable. "With the increasing prevalence of MASLD and MASH, the LHM platform provides essential support for clinicians seeking to catch the disease early, while it's still reversible," added Legros. "Our goal is to empower clinicians to intervene sooner, giving patients the best chance to improve their liver health, especially as more targeted treatments become available, such as Rezdiffra™, launched by Madrigal Pharmaceuticals earlier this year." For more information or to integrate the LHM platform into your practice, visit . About Echosens A pioneer in liver health, Echosens revolutionized liver diagnostics with FibroScan®, a non-invasive solution for comprehensive liver assessment. Validated by over 4,200 peer-reviewed publications and featured in 180+ international guidelines, FibroScan® is available in more than 127 countries, enabling millions of liver examinations worldwide. . Logo - WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

2024-11-03

·空之客

【药海听涛】全拿下，一扫光：GLP-1真的会杀死NASH市场吗？

自从这一波GLP-1火爆起来，几乎是一路从胜利走向胜利，不仅在T2D和减重这些基本盘，对心衰和慢性肾病等看似圈外领域，也都是风卷残云，看起来一副“VENI VIDI VICI”的姿态。于是每个不幸可能被GLP-1走过的角落，似乎注定逃不过寸草不生的命运，NASH就是长期以来被认为下一个“被GLP-1杀死的市场”。上周正好有两件NASH领域重要的里程碑事件先后出炉，让我们再审视一遍，NASH市场是否真的会被GLP-1全拿下一扫光？ 1 Sema治疗NASH到底能不能打？ 11月1日，Novo公布了Semaglutide治疗NASH的三期临床ESSENCE研究的初步结果，共入组了1,200例F2/3患者，按2:1分别每周一次给药2.4mg Semaglutide和安慰剂，本次公布的是前72周的病理结果。在72周内Sema与安慰剂相比，纤维化改善且NASH不恶化的比例是37.0% vs 22.5%，NASH缓解且纤维化不恶化的比例是62.9% vs 34.1%，两个终点都有显著性。看起来结果还是挺积极的，但问题是否足够制霸整个NASH领域了吗？先简单粗暴对比一下双终点的纸面数据不难发现，Sema本次Ph3数据与此前每日一次低剂量的Ph2b数据相比既没有惊喜也不算惊吓，相比于THRβ和FGF21等其他机制，Sema在纤维化终点依然没什么优势、反倒原本表现不错的NASH终点的优势被削弱了不少，至少很难说有碾压级的优势。特别是对于Madrigal的Resmetirom来说，从销售能力原本就跟Novo不在一个量级，一旦临床数据也被压一头的话可能就生存空间更加受限，而Sema目前的数据并没有体现出比Resmetirom有多大优势，这相当于给后者一个缓刑，无怪乎周五晚Madrigal又大涨了25%。再细看一下，本次ESSENCE研究的两个终点，Sema组在绝对值上（37.0%和62.9%）都是可圈可点，然而被安慰剂效应一反衬就显得泯然众人（22.5%和34.1%）。具体来说，纤维化终点上本次把安慰剂效应控制得不错，但Sema自己的响应率却不尽如人意，甚至不如自己的二期；NASH终点则是安慰剂效应高得过于离谱，在此前S/T药的NASH临床中都未曾见到，更是远远超出其他药物。于是，最终导致ESSENCE研究这两个终点的安慰剂修正结果都难称理想。当然，由于目前Novo只是出了一个PR，具体的分析集和统计学方法等细节都未披露（比如病理学评分的方式和脱落受试者的处理方法是不是与此前临床试验可比），对ESSENCE研究结果的定位还不能完全定论。 2 Madrigal的预期应该在哪儿？另外一边，Madrigal恰是提前一天10月31日发布了三季报，可以说是技惊四座。首先是最直观的销售额，上市后第一个季度$14.6m、第二个季度就爬到$62.2m，几乎是consensus的2倍以上；其次是患者数量，从上个季度的2,000迅速增长到这个季度的6,800，与销售额增长匹配，也与公司表达的库存很低相匹配；再次是对头部医生的处方覆盖，从上个季度的20%迅速提升到40%。最后也是最关键的信息，是在已覆盖80%商保的情况下，其中95%的支付可以接受无创检测而并不要求穿刺，从上市之前有关Resmetirom支付到底是否要求穿刺的争论基本上已经落定，最后的一丝悬念就看明年初Medicare的态度。腰杆子看起来硬了不少的Madrigal，居然开始了公屏嘲讽模式，直指Sema耐受性差不说，还yygq一顿“感谢Sema为我们打开了巨大市场空间、在它那么高的停药比例之后能留下足够多的二线患者”。 u1s1，这话刨掉情绪而论可能还挺值得玩味，虽然未见得就一定对谁有利。先必须要坦然承认，Sema正在成为NASH的一线标准疗法，证据包括下面（盗来的）payer调研结果以及连Madrigal也并没有否认这一趋势（他们只是阴阳了Sema耐受性差）；在接受这一现实的情况下，Resmetirom以及后续其他NASH药物完全有机会争取的生存空间就是联用GLP-1或者干脆就序贯治疗也没问题，那就推动着后续开发者要考虑这些setting，然而Resmetirom自己其实与GLP-1的协同作用并不算明显，所以压缩它空间的未必是GLP-1、反倒有可能是后续比如FGF-21等潜在与GLP-1协同更明显的玩家。对于Madrigal来说，阶段性的超预期引发了一个更加萦绕在全市场心头的疑问：为什么不赶紧把产品/公司卖掉？而公司对此的态度是截然相反，不仅没有出售的意思，反而是不断强调要以Resmetirom为起点长期深耕打造一个NASH帝国。这种在广阔适应症领域凭借一己之力做成biopharma的目标，固然热血但可行性实在不高（参见【医苑观畴】海外Biotech商业化的成败风云），最终能成功的那寥寥数人也都是要经历长时间和大规模的痛苦投入阶段：想当年Regeneron自己开始卖Eylea的时候，放量那四五年每年SG&A要烧$1b以上（那可是快10年前的购买力），这是凭借那几年公司市值高达$50b左右，增发两次融了$15b，以及Dupi提供的持续分成收益，才最终成就了Eylea的超重磅地位和Regeneron自己的传奇；就算是Alnylam自己卖TTR这么窄的品种，每年SG&A也要烧$800m，这也是凭借市值在$20b左右，连续增发好多轮融了$5b以上，才能撑得住如此不计血本的支出……而看看现在Madrigal也就$7b的市值（这还是在大涨之后），$1b的现金余额，每个季度只敢花$100m左右SG&A，就只有一种“这点钱够干啥的”捉襟见肘之感。综上所述，GLP-1想要一口吃下巨大的NASH市场目前看还缺付好牙口，包括Madrigal在内的玩家还有充足的施展空间，且目前初步的趋势也相当有利，至于选取何种切入口以及何种商业化模式，还有待探索和试错。往期NASH药物相关文章：【药海听涛】最后的烛火能否燃到黎明：NASH领域再现希望【药海听涛】弦歌不辍还是功败垂成：NASH药物近期主要进展【药海听涛】Madrigal鼙鼓动地来，惊破NASH羽衣曲【药海听涛】以往不谏，来者可追：NASH研发方向的新旧交替【药海听涛】GLP-1也不是万能的：2024年欧肝会NASH药物数据更新

ASH会议临床3期临床结果临床2期

2024-11-01

·Endpoints

Novo Nordisk claims late-stage MASH victory, continuing GLP-1's expansion

A day after Madrigal Pharmaceuticals impressed investors, Novo Nordisk is looking to steal the spotlight. The Danish drugmaker reported Friday that semaglutide succeeded in a Phase 3 study of patients with metabolic dysfunction-associated steatohepatitis (MASH), a form of advanced fatty liver disease and a burgeoning disease area for the GLP-1 class. Novo markets semaglutide as Wegovy for obesity and Ozempic for type 2 diabetes. Patients given 2.4 mg of semaglutide reported a statistically significant improvement in liver fibrosis without worsening of steatohepatitis in addition to resolution of steatohepatitis with no worsening of fibrosis — the two primary endpoints in the ESSENCE trial. At the 72-week mark, 37% of patients treated with 2.4 mg of semaglutide achieved liver fibrosis improvement compared to 22.5% on placebo, and 62.9% of patients on semaglutide achieved resolution of steatohepatitis, compared to 34.1% on placebo. Novo said that semaglutide was safe and well-tolerated in the study, producing a similar profile that’s been seen in the drug’s other trials. The company plans to file for approval in the US and EU in the first half of 2025 and present data at a scientific meeting later this year. The second part of the study remains on track for a readout in 2029. This was the readout that MASH drug developers were anxiously awaiting, given the ascension of the GLP-1 class and the proliferation of the drugs. Madrigal said Thursday that Rezdiffra, which was approved earlier this year, brought in an eye-popping $62.2 million in sales in the third quarter. But analysts still had questions about the potential for insurers to require that patients first take a GLP-1 before moving to a MASH-specific drug. “To date, we haven’t seen any requirement for step-through,” Madrigal CEO Bill Sibold said during Thursday’s earnings call, and he tried to reassure analysts that “topline readouts don’t always translate into labels so well.” “We’ll see what happens with the results of the trial to see what happens, if anything happens, with payers,” Sibold added. After an initial premarket selloff, Madrigal’s stock $MDGL rallied about 18% when the market opened Friday. The company’s shares have risen 41% since the end of Wednesday. The new Phase 3 data for semaglutide are a bounceback victory after the drug did not hit similar primary endpoints in a Phase 2 study last year. But because MASH is so prevalent among people with obesity, it’s been a hot disease area to tackle for companies with GLP-1 drugs. Despite the high price of GLP-1 drugs in the US, their annual list prices are significantly lower than Rezdiffra, which has a wholesale acquisition cost of $47,400 per year. But they’ve also been plagued by patchwork coverage and high dropout rates. Sibold sought to reinforce his confidence that payers would continue covering the drug, which became the first FDA-approved treatment for the underlying cause of MASH. “We feel like we’re in a very strong position as we go into any potential readout that takes place from ESSENCE,” he said.

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药物(靶点)	适应症	全球最高研发状态

瑞司美替罗 ( THR-β )	肝硬化更多	临床3期
PRCL-02 ( CRAC )	银屑病更多	临床2期
MGL-3745 ( THR-β )	II a型高脂蛋白血症更多	临床前
STA-9183 ( HSP90 )	肿瘤更多	临床前
Ganetespib ( HSP90 )	非小细胞肺癌IIIB期更多	终止