Saroglitazar

The European Commission has granted conditional approval for Ipsen's IQIRVO (elafibranor) for the treatment of primary biliary cholangitis in adults, marking the first new therapy for this condition to be approved in the EU in almost ten years. With this approval, other companies such as CymaBay Therapeutics, Zydus Therapeutics, GlaxoSmithKline, and others also geared up to bring their candidates into the primary biliary cholangitis market. LAS VEGAS, Oct. 2, 2024 /PRNewswire/ -- Primary biliary cholangitis (PBC), previously referred to as primary biliary cirrhosis, is a long-term liver condition characterized by the gradual destruction of the small bile ducts within the liver, known as intrahepatic bile ducts. Over time, prolonged bile flow obstruction can result in cirrhosis and the development of portal hypertension. As per DelveInsight analysis, in 2023, the total diagnosed prevalent cases of primary biliary cholangitis in the 7MM were approximately 298K. These cases are projected to increase further during the forecast period (2024–2034). In 2023, the United States had the highest proportion of diagnosed prevalent cases of primary biliary cholangitis among the 7MM, comprising approximately 48% of the total cases. DelveInsight's epidemiology model for primary biliary cholangitis estimates a higher prevalence among females across the 7MM. Specifically, in the US in 2023, it suggests approximately 25K cases among males and 117K cases among females, indicating a female predominance. The primary treatment objectives are to reduce the progression rate of the disease and manage symptoms such as itching, osteoporosis, and dry eye/mouth (sicca syndrome). Liver transplantation remains the only life-saving option. Ursodeoxycholic acid (UDCA) is the main medication used to slow disease progression. Patients in the early stages often experience clinical, biochemical, and histological improvements. Studies suggest UDCA postpones the need for liver transplantation and extends survival, though its effectiveness in advanced stages like cirrhosis is uncertain. While initially approved by the US FDA for treating primary biliary cholangitis, UDCA now has generic versions available. The use of corticosteroids in patients without signs of autoimmune hepatitis remains a subject of ongoing research. Studies have shown that combining UDCA with dexamethasone can enhance the activity of the anion exchanger from two alternate promoters in liver cells in vitro. Budesonide is being considered due to its extensive first-pass hepatic metabolism, which may help minimize side effects. Corticosteroids may help relieve symptoms and improve biochemical and histological outcomes, though corticosteroid-induced osteoporosis is a major concern. The criteria for liver transplantation in patients with primary biliary cholangitis are generally the same as those for other chronic liver diseases. However, severe and unmanageable itching is a unique reason for considering a transplant. Fatigue, which may continue after transplantation, is not regarded as an indication for the procedure. Liver transplantation for PBC patients typically offers a better prognosis than for most other chronic liver diseases, with a 5-year survival rate of 84–87% and a 10-year survival rate of 79–84%. In May 2016, the US FDA granted accelerated approval for OCALIVA (obeticholic acid) as a treatment for primary biliary cholangitis. It is approved for use alongside UDCA in adults who do not respond adequately to UDCA, or as a standalone treatment for those who cannot tolerate UDCA. OCALIVA is a semi-synthetic bile acid analog with the chemical structure 6α-ethyl-chenodeoxycholic acid. OCALIVA remains the only approved second-line therapy for this condition. Later, in December 2016, the European Commission gave conditional approval for OCALIVA for the same uses—either in combination with UDCA or as monotherapy for adults unable to tolerate UDCA. Learn more about the FDA-approved primary biliary cholangitis drugs @ Drugs for Primary Biliary Cholangitis Treatment Recently, the European Commission has granted conditional approval for IQIRVO (elafibranor) 80mg tablets for treating primary biliary cholangitis. It can be used alongside ursodeoxycholic acid in adults who have an inadequate response to UDCA or as a standalone therapy for those who cannot tolerate UDCA. This decision follows a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on July 26, 2024, and the US FDA's Accelerated Approval granted on June 10, 2024. Elafibranor, a pioneering molecule, has been marketed and commercialized in the US by Ipsen under the brand name IQIRVO since June 2024. It was originally developed by GENFIT, from its discovery through the completion of a 52-week Phase III clinical trial. In 2021, Ipsen obtained exclusive global rights to elafibranor, except for China, Hong Kong, Taiwan, and Macau, through a licensing agreement with GENFIT. The EU approval was based on favorable outcomes from the Phase III ELATIVE trial, which demonstrated a 47% clinical benefit of IQIRVO combined with UDCA compared to placebo plus UDCA on the composite primary endpoint. The main objective for cholestasis response was defined as alkaline phosphatase (ALP) being less than 1.67 times the upper limit of normal (ULN), with a ≥15% reduction in ALP and total bilirubin levels within the normal range after one year. Additionally, the treatment showed a reduction in pruritus when compared to placebo. Additionally, in August 2024, Gilead Sciences, Inc. announced that the FDA has granted accelerated approval for LIVDELZI (seladelpar) to treat primary biliary cholangitis. This treatment can be used alongside ursodeoxycholic acid in adults who have not responded adequately to UDCA or as a standalone therapy for those unable to tolerate UDCA. Livdelzi is not advised for patients with or who develop decompensated cirrhosis. Seladelpar (MBX-8025) is a potent and selective PPARδ agonist, administered orally, and is currently being developed for patients with PBC who either do not respond to or cannot tolerate UDCA. In March 2024, Gilead Sciences completed its acquisition of CymaBay and announced the validation of a Marketing Authorization Application (MAA) for Seladelpar by the European Medicines Agency (EMA). Seladelpar has been granted Breakthrough Therapy Designation (BTD) by the US FDA, PRIME status by the EMA, and Orphan Drug Designation (ODD) from both agencies, which may accelerate the approval process. To know more about primary biliary cholangitis treatment options, visit @ New Treatment for Primary Biliary Cholangitis With this approval, several companies have also geared up to bring their lead assets into the market. The expected launch of emerging therapies, such as Saroglitazar Magnesium (Zydus Therapeutics), Linerixibat (GlaxoSmithKline), Setanaxib (Calliditas Therapeutics AB), Bezafibrate + obeticholic acid (Intercept Pharmaceuticals/Alfasigma), Volixibat (Mirum Pharmaceuticals), EP547 (Escient Pharmaceuticals), and others are expected to create a positive impact on the market. Other therapies in the early stages of the trial are also being developed. Discover which therapies are expected to grab major primary biliary cholangitis market share @ Primary Biliary Cholangitis Market Report Saroglitazar (LIPAGLYN) comprises two primary types of PPAR agonists: PPARα (alpha) and PPARγ (gamma). This medication simultaneously reduces lipid and glucose levels, effectively decreasing elevated triglycerides and blood sugar while enhancing insulin sensitivity. The US FDA has awarded Saroglitazar orphan drug designation (ODD) and fast track designation (FTD) for primary biliary cholangitis (PBC). It is presently undergoing Phase II/III trials for this condition. Linerixibat (GSK2330672) is a medication under development for patients with primary biliary cholangitis who suffer from itching. It is a small molecule inhibitor of the ileal bile acid transporter (IBAT) that is minimally absorbed and taken as an oral tablet. By preventing the reabsorption of bile acids in the small intestine, linerixibat lowers the levels of pruritic bile acids in the bloodstream. In 2019, the FDA designated it as an orphan drug (ODD). It is currently being evaluated in a Phase III trial for treating cholestatic pruritus in individuals with PBC. Discover more about drugs for primary biliary cholangitis in development @ Primary Biliary Cholangitis Clinical Trials The anticipated launch of these emerging therapies for primary biliary cholangitis are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the primary biliary cholangitis market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the primary biliary cholangitis market saw a significant emergence of a dominant treatment modality, valued at USD 1.1 billion in the 7MM. This modality likely reflects advancements in therapeutic approaches such as first-line agents like UDCA, second-line treatments like obeticholic acid, and potentially emerging biologics or combination therapies aiming to address the complex pathophysiology of PBC, thus enhancing patient outcomes and market share. DelveInsight's latest published market report titled as Primary Biliary Cholangitis Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the primary biliary cholangitis country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The primary biliary cholangitis market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent cases of Primary Biliary Cholangitis Gender-specific Diagnosed Prevalent cases of Primary Biliary Cholangitis Age-specific Diagnosed Prevalent cases of Primary Biliary Cholangitis The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM primary biliary cholangitis market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis up to 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this primary biliary cholangitis market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the primary biliary cholangitis market. Also, stay abreast of the mitigating factors to improve your market position in the primary biliary cholangitis therapeutic space. Related Reports Primary Biliary Cholangitis Pipeline Primary Biliary Cholangitis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key PBC companies, including Genfit, Zydus Discovery, Ohara Pharmaceutical, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Novartis, CymaBay Therapeutics, among others. Primary Biliary Cholangitis Epidemiology Forecast Primary Biliary Cholangitis Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and PBC epidemiology trends. Liver Cirrhosis Market Liver Cirrhosis Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key liver cirrhosis companies, including Madrigal Pharmaceuticals, Inc., Galectin Therapeutics Inc., Grifols Therapeutics LLC, CymaBay Therapeutics, Akero Therapeutics, Inc., NGM Biopharmaceuticals, Inc., Gilead Sciences, Novo Nordisk A/S, Cellaion, Promethera Therapeutics, Lipocine Inc., Bristol Myers Squibb, Prism Pharma, Ohara Pharmaceutical, Shionogi, among others. Liver Cirrhosis Pipeline Liver Cirrhosis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key liver cirrhosis companies, including Versantis AG, Mirum Pharmaceuticals, Sagimet Biosciences, TenNor Therapeutics, Prism Pharma, Vedanta Biosciences, Intercept Pharmaceuticals, Boehringer Ingelheim, Ohara Pharmaceutical, Ocelot Bio, Calliditas Therapeutics, Galecto Biotech, Pharmicell, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

●Iqirvo（elafibranor）80毫克片剂是近十年来首个获批用于治疗罕见肝病原发性胆汁性胆管炎的新药 ●基于ELATIVEIII期临床试验的积极数据而获得批准 ●原发性胆汁性胆管炎影响美国约10万人，全球患病率正在上升；治疗不当可能会导致肝功能衰竭 ●Iqirvo在美国获批，确立益普生在罕见胆汁淤积性肝病治疗领域的领先地位 Jiuzhou News          6月10日，益普生宣布美国食品药品监督管理局（FDA）已加速批准Iqirvo（elafibranor）80毫克片剂与熊去氧胆酸（UDCA）联合用于治疗对UDCA反应不足的成人原发性胆汁性胆管炎（PBC），或作为单药治疗无法耐受UDCA的患者。Iqirvo可立即在美国为符合条件的患者开具处方。 这一适应症的加速获批基于elafibranor对于碱性磷酸酶（ALP）的降低作用，尚未证实该药物可改善生存率或预防肝功能恶化事件的发生。这一适应症的继续批准，可能取决于确认性试验中对临床益处的验证结果。不建议患有或发展为失代偿性肝硬化（例如腹水、静脉曲张出血、肝性脑病）的人使用。Iqirvo不推荐用于患有或发展出失代偿期肝硬化（如腹水、静脉曲张出血、肝性脑病）的人群。 Elafibranor是一款同类首创、口服（每日一次）的过氧化物酶体增殖物激活受体（PPAR）激动剂，是益普生在2021年从GENFIT公司引进。Elafibranor的加速批准是基于发表在《新英格兰医学杂志》上III期ELATIVE试验结果。ELATIVE研究表明，接受elafibranor加UDCA治疗（n=108），达到生化反应综合主要终点的患者比例是接受安慰剂加UDCA治疗（n=53）的13倍（分别为51%和4%，相差47%）。ALP是一种生化标志物，在PBC试验中用作替代终点。次要终点显示，只有接受elafibranor治疗的患者的ALP水平恢复正常，elafibranor+UDCA组为15%，而安慰剂+UDCA组为0%。大多数患者（95%）接受了研究药物（elafibranor或安慰剂）与UDCA的联合治疗。 最常见（≥10%）的elafibranor不良反应是体重增加、腹痛、腹泻、恶心和呕吐，部分接受elafibrano治疗的研究参与者出现肌肉疼痛、肌无力、横纹肌溶解症、骨折、胎儿和新生儿发育潜在的不良影响、药物引起的肝损伤、过敏反应、胆道阻塞。 PBC是一种罕见的自身免疫性胆汁淤积性肝病，胆汁和毒素积聚（胆汁淤积）以及慢性炎症导致肝脏不可逆性纤维化（瘢痕化）和胆管破坏。PBC为终生的疾病，在美国大约有10万人受到影响，其中大多数是女性，如果不能得到有效治疗，随着时间的推移可能会恶化，导致需要肝移植，甚至在某些情况下会导致过早死亡。PBC还会影响日常生活，患者最常见的症状是严重疲劳和难以忍受的瘙痒（瘙痒感）。 Elafibranor已向欧洲药品管理局（EMA）和英国药品和保健品管理局（MHRA）提交，寻求批准用于治疗PBC。预计EMA和MHRA将在2024年下半年做出最终监管决定。 小结 过氧化物酶体增殖物激活受体（PPAR）是一种配体激活型转录因子，已确定的三种亚型包括PPARα、 PPARδ/β、 PPARγ。其中，PPARα在肝脏中高度表达，广泛参与体内能量代谢、氧化应激、炎症等多种生物活动；PPARγ在各种脂肪组织中广泛表达，参与脂质代谢活动；PPARβ则被发现在抑制炎症反应发生方面发挥作用。 目前，已有多款PPAR激动剂获批上市：贝特类药物是最具代表性的PPAR-α激动剂，包括吉非贝齐、非诺贝特、苯扎贝特和培马贝特，用于治疗动脉粥样硬化和血脂异常；PPAR-γ激动剂主要为噻唑烷二酮类，用于治疗２型糖尿病（T2MD），如吡格列酮、曲格列酮、罗格列酮；PPAR-α/γ双激动剂沙罗格列扎，在印度获批用于血酯异常和高甘油三酯、非酒精性脂肪肝；PPAR-α/β/γ全激动剂西格列他钠，由微芯生物研发在国内获批用于T2MD的治疗。 ▲图1 获批上市的PPAR激动剂 PPAR除了在糖尿病、心血管疾病的临床应用之外，PPAR的功能调节还能够改善各种原因引起的肝脏疾病，包括病毒性肝炎、非酒精性脂肪性肝病、胆汁淤积性肝病、肝纤维化、肝细胞癌、药物性肝炎等。PPAR激动剂主要通过减少脂质沉积、调节炎症反应的手段，参与肝脏疾病治疗发挥作用，在肝病治疗领域展现出巨大潜力。 ▲图2 PPAR参与肝脏疾病的分子机制 PPAR激动剂在肝病领域的开发，目前非酒精性脂肪肝（NASH）、原发性胆汁性胆管炎（PBC）两项适应症进展较快。海外开发中，除益普生Elafibranor外，礼来/武田共同开发的吡格列酮正在开展T2MD伴有NASH的4期临床研究；Inventiva开发的Lanifibranor处于治疗NASH的III期临床阶段；Cadila的沙罗格列扎已在印度获批用于NASH治疗，并在美国开展NASH、PBC的II期临床；Poxel公司的氘代R-吡格列酮也在II期临床获得积极结果。 ▲图3 PPAR激动剂在肝脏疾病中的临床研发进展 国内参与者包括微芯生物、正大天晴、拓臻生物。其中，微芯生物为自主研发的PPARα/β/γ全激动剂，正在开展NASH治疗II期临床；正大天晴在2022年以1200万美元的首付款及最高不超过4000万美元的里程碑，引入Lanifibranor在大中华区的独家许可，已在国内登记NASH III期临床；拓臻生物于2019年以3500万美元首付款以及不高于1.93亿美元的里程碑，获得elafibranor大中华区的独家权益，目前尚未查询到国内临床进展。 ▲图4 文中PPAR激动剂结构式 免责申明 本公众号注明原创的内容权利均属九洲药业所有，未经授权，不得擅自使用或许可他人使用。如需获得授权，请和九洲药业提前联系。已获得授权的，应在授权范围内使用，并注明来源且不得再全部或部分转授权他人。 本公众号对转载、分享的内容、陈述、观点判断保持中立，不对所包含内容的合法性、准确性、可靠性或完善性提供任何明示或暗示的保证，该等内容版权归原作者所有，仅供学习参考之用，若对转载、分享的内容有任何权利疑问，烦请联系九洲药业。