Cholelithiasis

CONSHOHOCKEN, Pa., Oct. 30, 2024 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a biopharmaceutical company focused on delivering novel therapeutics for nonalcoholic steatohepatitis (NASH)/metabolic dysfunction-associated steatohepatitis (MASH), today announced multiple resmetirom data presentations at the upcoming American Association for the Study of Liver Diseases (AASLD) Liver Meeting, taking place from November 15-19, 2024 in San Diego. Bill Sibold, Chief Executive Officer of Madrigal, stated, “This will be the first AASLD Liver Meeting following the approval of Rezdiffra earlier this year, and the entire NASH community feels energized with new momentum. It is an exciting moment for Madrigal and for the field as a whole. At the same time, we recognize that NASH remains the leading cause of liver transplant among women in the U.S. and second-leading cause in men, so there is an urgent need to continue advancing patient care. The Liver Meeting will provide a valuable opportunity to share the latest resmetirom clinical research, engage with healthcare providers, and reinforce Madrigal’s leadership position in NASH.” Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, added, “The eleven abstracts Madrigal will be presenting at The Liver Meeting support Rezdiffra’s position as the foundational therapy for NASH with moderate to advanced fibrosis and offer important insights into the burden of the disease on patients and the health system. We look forward to sharing two oral presentations of new results from the Phase 3 MAESTRO-NASH trial and multiple posters from our clinical development program that will help guide patient care and further NASH research.” Rezdiffra (resmetirom) is a once-daily, oral, liver-directed thyroid hormone receptor THR-β agonist designed to target key underlying causes of NASH. It is the first approved medication for the treatment of NASH. In the pivotal Phase 3 MAESTRO-NASH biopsy trial, Rezdiffra achieved both fibrosis improvement and NASH resolution primary endpoints, and 80% of patients treated with Rezdiffra 100 mg experienced improvement or stabilization of fibrosis. Rezdiffra is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials. Madrigal data presentations at AASLD The Liver Meeting, 2024 Oral presentation: “Effect of resmetirom or placebo in NASH fibrosis patients with <5% or ≥5% weight loss and/or on baseline GLP-1 therapy in the MAESTRO-NASH 52-week serial liver biopsy study” [Sunday, Nov. 17 at 9:15 a.m. PST. Presenter: Mazen Noureddin]Oral presentation: “Resmetirom effects on NASH with liver fibrosis in patients with NASH genetic risk alleles” [Sunday, Nov. 17 at 11:30 a.m. PST. Presenter: Naga Chalasani]Poster: “Resmetirom therapy of MASH-associated Child Pugh A cirrhosis reduces estimated risk for clinical outcome based on HepQuant RISK ACE model” [Presenter: Gregory Everson]Poster: “Baseline characteristics in well-compensated NASH cirrhosis patients diagnosed with or without a liver biopsy in MAESTRO-NASH-OUTCOMES, a clinical outcome Phase 3 study assessing the effect of resmetirom in well compensated NASH cirrhosis” [Presenter: Meena Bansal]Poster: “Use of non-invasive tests to diagnose and follow NASH with liver fibrosis patients treated with resmetirom” [Presenter: Naim Alkhouri]Poster: “Liver enzymes reductions from baseline over time in resmetirom treated patients in a Phase 3 study, MAESTRO-NASH” [Presenter: Seth Baum]Poster: “Validating pre-identified morphological baseline features for predicting fibrosis progression in MAESTRO-NASH” [Presenter: Jörn Schattenberg]Poster: “Impact of resmetirom on statin pharmacokinetics and safety in Phase 1 studies and MAESTRO-NASH” [Presenter: Seth Baum]Poster: “Assessment of resmetirom efficacy (80 mg vs. 100 mg) stratified by baseline body mass index and weight in patients from the MAESTRO-NASH trial” [Presenter: Mazen Noureddin]Poster: “Risk of incident extrahepatic cancers among Medicare patients with non-alcoholic steatohepatitis (NASH)” [Presenter: Robert Gish]Poster: “Current multi-dimensional view of non-alcoholic steatohepatitis (NASH)/ metabolic dysfunction-associated steatohepatitis (MASH) global epidemiological rates” [Presenter: Michael Charlton] Additionally, Madrigal will be exhibiting at booth #1239 and hosting two product theaters on Sunday and Monday, November 17 and 18, at 10:00 a.m. PST. About NASH Nonalcoholic steatohepatitis (NASH) is a more advanced form of nonalcoholic fatty liver disease (NAFLD). NASH is a leading cause of liver-related mortality and an increasing burden on healthcare systems globally. Additionally, patients with NASH, especially those with more advanced metabolic risk factors (hypertension, concomitant type 2 diabetes), are at increased risk for adverse cardiovascular events and increased morbidity and mortality. Once patients progress to NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), the risk of adverse liver outcomes increases dramatically. When a patient with NASH progresses to cirrhosis, their risk of liver-related mortality increases by more than 42 percent. NASH is rapidly becoming the leading cause of liver transplantation in the U.S. Madrigal estimates that approximately 1.5 million patients have been diagnosed with NASH in the U.S., of which approximately 525,000 have NASH with moderate to advanced liver fibrosis. Madrigal is focusing on approximately 315,000 diagnosed patients with NASH with moderate to advanced liver fibrosis under the care of liver specialist physicians during the launch of Rezdiffra. NASH is also known as metabolic dysfunction-associated steatohepatitis (MASH). In 2023, global liver disease medical societies and patient groups came together to rename the disease, with the goal of establishing an affirmative, non-stigmatizing name and diagnosis. Nonalcoholic fatty liver disease (NAFLD) was renamed metabolic dysfunction-associated steatotic liver disease (MASLD); NASH was renamed MASH; and an overarching term, steatotic liver disease (SLD), was established to capture multiple types of liver diseases associated with fat buildup in the liver. In addition to liver disease, patients with MASH have at least one related comorbid condition (e.g., obesity, hypertension, dyslipidemia, or type 2 diabetes). About Rezdiffra What is Rezdiffra? Rezdiffra is a prescribed medicine used along with diet and exercise to treat adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver. It is not known if Rezdiffra is safe and effective in children (under 18 years old). This indication is approved based on improvement of NASH and liver scarring (fibrosis). There are ongoing studies to confirm the clinical benefit of Rezdiffra. Before you take Rezdiffra, tell your healthcare provider about all of your medical conditions, including if you: have any liver problems other than NASH.have gallbladder problems or have been told you have gallbladder problems, including gallstones.are pregnant or plan to become pregnant. It is not known if Rezdiffra will harm your unborn baby.are breastfeeding or plan to breastfeed. It is not known if Rezdiffra passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Rezdiffra. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Rezdiffra and other medicines may affect each other, causing side effects. Rezdiffra may affect the way other medicines work, and other medicines may affect how Rezdiffra works.Especially tell your healthcare provider if you take medicines that contain gemfibrozil to help lower your triglycerides, or cyclosporine to suppress your immune system, because Rezdiffra is not recommended in patients taking these medicines.Tell your healthcare provider if you are taking medicines such as clopidogrel to thin your blood or statin medicines to help lower your cholesterol.Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. What are the possible side effects of Rezdiffra? Rezdiffra may cause serious side effects, including: liver injury (hepatotoxicity). Stop taking Rezdiffra and call your healthcare provider right away if you develop the following signs or symptoms of hepatotoxicity: tiredness, nausea, vomiting, fever, rash, your skin or the white part of your eyes turns yellow (jaundice), pain or tenderness in the upper middle or upper right area of your stomach (abdomen). gallbladder problems. Gallbladder problems such as gallstones, inflammation of the gallbladder, or inflammation of the pancreas from gallstones can occur with NASH and may occur if you take Rezdiffra. Call your healthcare provider right away if you develop any signs or symptoms of these conditions including nausea, vomiting, fever, or pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen to your back and the pain may happen with or without vomiting. The most common side effects of Rezdiffra include: diarrhea, nausea, itching, stomach (abdominal) pain, vomiting, dizziness, constipation. These are not all the possible side effects of Rezdiffra. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Madrigal at 1-800-905-0324. Please see the full Prescribing Information, including Patient Information, for Rezdiffra. About Madrigal PharmaceuticalsMadrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a biopharmaceutical company focused on delivering novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal’s medication, Rezdiffra (resmetirom), is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of NASH. For more information, visit www.madrigalpharma.com. Forward-Looking StatementsCertain statements in this press release, other than purely historical information, may constitute “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including statements regarding: Rezdiffra and its expected use for treating NASH with moderate to advanced fibrosis. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Madrigal’s control, and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties and other factors are described under the heading “Risk Factors” in Madrigal’s Annual Report on Form 10-K for the year ended December 31, 2023, and Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, and in subsequent filings made by Madrigal with the Securities and Exchange Commission from time to time. These forward-looking statements are based on Madrigal's current expectations and speak only as of the date of this press release. Except as required by law, Madrigal undertakes no obligation to update any forward-looking statements to reflect new information, events, or circumstances after the date they are made, or to reflect the occurrence of unanticipated events. Investor Contact Tina Ventura, IR@madrigalpharma.com Media ContactChristopher Frates, media@madrigalpharma.com

针对不断出现的替尔泊肽仿冒产品，礼来进一步采取了法律行动。 近日，礼来对三家替尔泊肽的供应商提起了诉讼，因为这三家供应商提供未经FDA批准的仿冒替尔泊肽，公司寻求法院下令停止这些替尔泊肽仿冒产品的销售，并要求这些供应商给予经济赔偿。 假冒药的横行 GLP-1需求的飙升不仅使诺和诺德和礼来成为欧洲最有价值的公司之一，也导致了全球各地长期供应短缺的现象，为了从中分得一杯羹，一些违法商家对两家公司的产品进行了大肆的仿冒和伪造。这些未经严格监管的仿冒药对患者的健康构成重大的风险，严重的可能危及生命。 去年12月，FDA在其官网发布公告，查获了数千支假冒美格鲁肽注射剂，FDA建议批发商、零售药店不要分发、使用或销售印有生产批号为NAR0074的仿冒产品。 在NAR0074批次中，用的是真的司美格鲁肽，但其注射针头是假的，无菌性未知。 存在更大安全隐患的是假药，一些非法商家通过伪造的药品生产批号来非法兜售假药。 如生产编号为MP5B060的司美格鲁肽中就混入了大量假药，这些假药的活性成分是胰岛素，只是被重新贴标签和包装为了司美格鲁肽。据调查，混入MP5B060批次中的假药至少已经在英国、墨西哥、孟加拉国、伊拉克、黎巴嫩等11个国家流通。 服用这类假药会给患者造成重大的安全风险，注射过量胰岛素会导致血糖或葡萄糖水平过低，患上低血糖症，严重者可能发展为意识丧失或癫痫发作。 2023年7月，世界卫生组织已经对MP5B060批次混入假药发出了警告，一些国家/地区甚至已经禁止使用带有该生产编号的产品。 复方药物的风险 此外，未经监管批准的复方药物同样存在重大的健康风险。 复方药物是FDA为了解决“上市药物短缺以及特定个体患者的临床需求”允许有执照的药房自行配制配方、剂量和给药方式的做法。 然而在一些药房配制的复方药物中，其活性成分过少、过多或根本没有，更甚者含有错误或有害的成分。 这些复方药物造成了一些患者的错误用药，症状轻微的一些患者出现胃肠道反应、晕厥、脱水、头痛、胆结石和急性胰腺炎，而严重的甚至需要住院治疗。 据统计，今年8月31日，FDA表示其收到了346份复方司美格鲁肽不良事件报告，以及136份复方替尔泊肽不良事件报告，这其中有很大一部分与服用了错误的药物剂量有关。 2024年3月，礼来表示不向任何复方药店提供Mounjaro和Zepbound的活性成分—替尔泊肽。2024年5月，澳大利亚政府宣布全面禁止复方替尔泊肽。最近，诺和诺德也向FDA要求禁止司美格鲁肽的复方药物。 参考出处 https://www.benzinga.com/news/24a10/41436151/eli-lilly-sues-some-vendors-for-unauthorized-sale-of-fake-weight-loss-drug https://www.drugdiscoverytrends.com/lilly-novo-nordisk-battle-surge-in-copycat-weight-loss-drugs-amid-safety-concerns/ 司美格鲁肽假药风险高，FDA再次发布预警

Terns Pharmaceuticals is making headlines with promising early results from its experimental GLP-1 obesity drug, which led to a 5.5% reduction in body weight in a small study. Positioned as a potential oral alternative to popular injectable weight loss medications like Ozempic, this new drug may soon offer another option for those seeking medical interventions for obesity. With larger trials on the horizon, the excitement around pharmaceutical treatments for weight loss continues to grow. The economic impact of weight loss medications on healthcare systems Pharmaceutical treatments like Wegovy and Ozempic have demonstrated significant potential in reducing body weight, but their high costs pose challenges for both patients and the broader healthcare system. With prices reaching up to $1,349 per month for Wegovy and around $1,000 for Ozempic, access to these medications is often restricted to those with comprehensive insurance. Even for patients with insurance, out-of-pocket costs can still amount to hundreds of dollars monthly, creating a substantial financial burden for many. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum This cost barrier raises concerns about worsening health disparities, particularly among low-income and underserved populations. Medicaid and Medicare beneficiaries are far less likely to access these medications, as Medicare Part D typically does not cover weight-loss drugs unless the patient also has a chronic condition like heart disease. This lack of coverage leaves many patients without a traditional solution. In addition to the cost, the side effects of these drugs are another factor prompting some patients to seek alternative approaches. Common side effects of weight-loss drugs like Ozempic and Wegovy include nausea, diarrhea, and constipation, with more severe risks such as gallstones, thyroid complications, and even cancer in some cases. These potential health risks have spurred growing interest in more holistic approaches to weight management, with the U.S. alternative medicine industry experiencing significant growth — from $21.7 billion in 2013 to an estimated $30.6 billion in 2023. For employers and insurers, the rising popularity of weight-loss treatments also has financial implications. As companies consider offering coverage for these high-cost medications, they must balance short-term expenses with potential long-term savings from treating obesity-related conditions. For some organizations, incorporating more cost-effective options, such as herbal supplements, into employee benefit plans may provide a viable solution, particularly given the growing demand for natural health products. The role of herbs for weight loss presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB The science behind herbal remedies for weight management is still evolving. While pharmaceutical options like Ozempic have undergone rigorous clinical trials and are backed by strong evidence, herbal alternatives lack the same level of scientific scrutiny. However, early research suggests that certain herbs may provide metabolic benefits. Adaptogens, a class of herbs gaining attention, offer a unique approach to supporting the body through stress. Adaptogens are known for their ability to help the body adapt to various stressors — be they physical, chemical, or biological. Although they are not specifically marketed as weight loss solutions, adaptogens can indirectly influence weight loss by addressing factors like hormonal imbalances and chronic stress. For example, prolonged stress triggers the production of cortisol, a hormone associated with fat accumulation, especially around the abdomen. By helping to regulate cortisol levels, adaptogens like ashwagandha, rhodiola, and holy basil promote hormonal balance, which may contribute to weight management as a secondary benefit. In addition to managing cortisol, studies suggest that adaptogens may activate genes that protect cells from damage during stress, further supporting overall bodily balance. While adaptogens are not a direct solution for weight loss, their ability to reduce stress — one of the main contributors to weight gain — makes them an intriguing part of a holistic approach to weight management. Berberine-rich herbs have also been gaining attention in the weight loss arena, often referred to as “Nature’s Ozempic” due to their potential to support metabolic health. Herbs like barberry root bark, goldenseal root, and Oregon grape root are particularly noted for their berberine content. Studies highlight berberine’s ability to activate AMP-activated protein kinase (AMPK), a key regulator of glucose metabolism and fat breakdown. Despite its nickname, berberine functions differently from medications like Ozempic, Wegovy, and Mounjaro, which are GLP-1 receptor agonists. These drugs suppress appetite by slowing digestion and increasing insulin production. In contrast, berberine activates AMP-activated protein kinase (AMPK), an enzyme that plays a crucial role in regulating energy use and fat metabolism. However, while these findings are encouraging, further research is needed to confirm berberine’s long-term efficacy and safety for weight loss. Offering choices: the compassionate approach to patient care For patients who may be unable to afford the high cost of GLP-1 obesity drugs or are worried about the side effects, it’s important for healthcare providers to offer education on herbal alternatives and consider these as part of the broader treatment conversation. While herbal options may not produce the same clinical outcomes as pharmaceuticals like Wegovy or Ozempic, they can still serve as valuable components of a comprehensive weight management strategy, particularly for those seeking more accessible or lower-cost options. By presenting herbal treatments as complementary or supportive measures, providers empower patients to make informed, individualized choices that account for both health and financial considerations. This inclusive approach ensures that patients from diverse socioeconomic backgrounds can explore effective weight management solutions, even when high-cost medications may be out of reach.