A Phase 2a, Randomized, Blinded, Placebo-controlled Study of BOS-580 in Obese Subjects At Risk For, or with Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) with a Single Arm Open-label Extension

This is a randomized, blinded, placebo-controlled study of Efimosfermin in obese participants at risk for, or with biopsy-confirmed, nonalcoholic steatohepatitis (NASH), with a single arm open-label extension. It includes Parts A, B, C and D.

开始日期2021-09-30

申办/合作机构

Boston Pharmaceuticals, Inc.初创企业

NCT03466203

/ Completed临床1期

A 12 Week Phase Ib Randomized Investigator and Subject Blinded Placebo Controlled Repeat-dose Study of LLF580

The purpose of the study is to evaluate the safety and tolerability of multiple doses of LLF580 administered subcutaneously over 3 months in obese subjects. In addition, the study will also determine early efficacy signals in various metabolic diseases associated with elevated triglycerides and/or obesity.

开始日期2018-02-26

申办/合作机构

Novartis Pharmaceuticals Corp.

100 项与 Efimosfermin alfa 相关的临床结果

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100 项与 Efimosfermin alfa 相关的转化医学

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100 项与 Efimosfermin alfa 相关的专利（医药）

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项与 Efimosfermin alfa 相关的文献（医药）

2022-01-01·The Journal of Clinical Endocrinology & Metabolism2区 · 医学

LLF580, an FGF21 Analog, Reduces Triglycerides and Hepatic Fat in Obese Adults With Modest Hypertriglyceridemia

2区 · 医学

Article

作者: Ferriere, Michael ; Diener, John ; Wilson, Jessica ; Bajaj, Archna ; Hinder, Markus ; Maratos-Flier, Eleftheria ; Yowe, David ; Koren, Michael ; Escalon, Maricer ; Fein, Melanie ; Nguyen, Amanda ; Rader, Daniel J ; Hom, Doug ; Kompa, Jill ; Kankam, Martin K ; Martic, Miljen ; Li, Yifang ; Basson, Craig T ; Hunt, Allen ; Goldfine, Allison B

AbstractPurposeTo evaluate the safety and potential efficacy of LLF580, a genetically engineered variant of human fibroblast growth factor-21, for triglyceride lowering, weight loss, and hepatic fat reduction.MethodsA multicenter, double-blind, parallel design trial in obese, mildly hypertriglyceridemic adults randomized (1:1) to LLF580 300 mg or placebo subcutaneously every 4 weeks for 3 doses.ResultsOf 64 randomized study participants, 61 (mean ± SD: age 45 ± 11 years, 49% male, 80/15/5% Caucasian/African American/other, body mass index 36.1 ± 3.8 kg/m2) received LLF580 (n = 30) or placebo (n = 31) at 7 research sites in the United States. LLF580 lowered serum triglycerides by 54% (least square mean placebo adjusted change from baseline), total cholesterol 7%, low-density lipoprotein cholesterol 12%, and increased high-density lipoprotein cholesterol 36% compared with placebo (all P < 0.001) over 12 weeks. Substantial reduction of liver fat of 52% over placebo (P < 0.001) was also demonstrated in the setting of improved liver function tests including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, the composite enhanced liver fibrosis score, and N-terminal type III collagen propeptide (all P < 0.05). Insulin and C-peptide levels and insulin resistance by homeostatic model assessment for insulin resistance were all lower, and adiponectin higher with LLF580 treatment compared with placebo, whereas fasting glucose and glycated hemoglobin were unchanged. Reductions in biomarkers of bone formation without differences in markers of bone resorption were observed. LLF580 was generally safe and well tolerated, except for higher incidence of generally mild to moderate gastrointestinal adverse effects.ConclusionsIn obese, mildly hypertriglyceridemic adults, LLF580 was generally safe and demonstrated beneficial effects on serum lipids, liver fat, and biomarkers of liver injury, suggesting it may be effective for treatment of select metabolic disorders including hypertriglyceridemia and nonalcoholic fatty liver disease. Assessments of longer term safety and efficacy are warranted.ClinicalTrials.gov IdentifierNCT03466203

Therapeutics and Clinical Risk Management

Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Review

作者: Mantzoros, Christos S ; Polyzos, Stergios A ; Raptis, Dimitrios D

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease without any approved treatment to-date despite intensive research efforts by researchers and pharmaceutical industry. Fibroblast growth factor (FGF)-21 has been gaining increasing attention as a possible contributing factor and thus therapeutic target for obesity-related metabolic disorders, including NAFLD, mainly due to its effects on lipid and carbohydrate metabolism. Most animal and human observational studies have shown higher FGF-21 concentrations in NAFLD than non-NAFLD, implying that FGF-21 may be increased to counteract hepatic steatosis and inflammation. However, although Mendelian Randomization studies have revealed that variations of FGF-21 levels within the physiological range may have effects in hyperlipidemia and possibly nonalcoholic steatohepatitis, they also indicate that FGF-21, in physiological concentrations, may fail to reverse NAFLD and may not be able to control obesity and other diseases, indicating a state of FGF-21 resistance or insensitivity that could not respond to administration of FGF-21 in supraphysiological concentrations. Interventional studies with FGF-21 analogs (eg, pegbelfermin, efruxifermin, BOS-580) in humans have provided some favorable results in Phase 1 and Phase 2 studies. However, the definite effect of FGF-21 on NAFLD may be clarified after the completion of the ongoing clinical trials with paired liver biopsies and histological endpoints. The aim of this review is to critically summarize experimental and clinical data of FGF-21 in NAFLD, in an attempt to highlight existing knowledge and areas of uncertainty, and subsequently, to focus on the potential therapeutic effects of FGF-21 and its analogs in NAFLD.

项与 Efimosfermin alfa 相关的新闻（医药）

2025-03-14

·EndPoints

Boston Pharma, building off MASH momentum, mulls an IPO ahead of Phase 3 trial

The once-fledgling field of MASH drug developers is now one of the few areas of consistency in the biotech industry. And another late-stage startup is gaining traction. Boston Pharmaceuticals, advancing a once-monthly liver disease drug, is exploring both an IPO and an acquisition, looking to capitalize after a successful mid-stage trial and a comparable company’s positive data. “We are focusing on being de-risked and fast, but we’re also doing [a] dual track,” Boston Pharma CEO Sophie Kornowski told Endpoints News in an interview. “It’s important for us to have smart investors at the table. You want to maximize the asset for the patients.” Mayank Mamtani, senior managing director and group head of healthcare at B Riley Securities, compared Boston to the cardiometabolic biotech Carmot Therapeutics. In 2023, that company raised $150 million in May, filed paperwork to go public in mid-November, and was swiftly acquired by Roche two weeks later. “They could kind of do these parallel processes and see what makes sense from a timeline to value creation,” he said in an interview. Boston’s plans underscore just how much momentum biotechs have gained by looking to treat metabolic dysfunction-associated steatohepatitis, a form of advanced fatty liver disease also known as NASH. A few years ago, the treatment landscape was a graveyard. Now, there’s an approved drug in Madrigal’s once-daily pill Rezdiffra, and a number of followers that confidently feel there’s enough of the market that awaits them. Boston Pharma launched 10 years ago with $600 million when megarounds genuinely were a dime a dozen. It had the backing of Gurnet Point Capital, led then by current Biogen CEO Chris Viehbacher, and was helmed by former Eli Lilly executive Robert Armstrong. Not unlike many bright-eyed biotechs, Boston Pharma wanted to win at everything. It strove to have 20 clinical assets, and licensed a handful from GSK and Novartis in 2018. Another asset separately licensed from the Swiss pharma in 2020 was what became efimosfermin alfa, now the only asset in its clinical pipeline. Kornowski, a dealmaker in her own right after previously leading Roche’s BD team, said “the economics are really favorable to Boston Pharmaceuticals.” Board chairman Elias Zerhouni told Endpoints that when he got involved, he convinced investors that the company had to focus. “You can’t afford to not be best-in-class in at least one category, if not two,” he recalled telling Ernesto Bertarelli, an Italian billionaire whose asset management firm includes Gurnet Point. So the company focused on the MASH treatment. Boston Pharma reported Phase 2 data in November showing statistically significant improvements in both fibrosis without worsening of MASH, and resolution of MASH without worsening of fibrosis. Fibrosis is a type of liver scarring that’s a hallmark of the disease. Its drug got another boost after Akero Therapeutics reported in late January that its own candidate with a similar mechanism was able to better reverse advanced fibrosis in patients compared to placebo. Zerhouni says that those data not only validated the broader FGF21 class, but they informed how vital the duration of therapy is. “They set up a threshold for everybody,” he said. “We think we have what it takes to equal or better this particular threshold that they came up with.” Akero is testing its drug as a once-weekly treatment, and fellow FGF21-targeting biotech 89bio is testing weekly or every two-week dosing. Mamtani compared Boston’s once-monthly efimosfermin alfa to Amgen’s obesity drug MariTide, which is similarly leaning on convenience to compete with other weight loss drugs. “Longer-acting mechanism, very potent fat reduction, less drug exposure, maybe that bone [toxicity] risk can be kind of ruled out,” Mamtani said. “So those are things that, from a clinical profile standpoint, make the case” for the drug, he added. Boston Pharma has some catching up to do, with Akero and 89bio both in Phase 3 studies. It expects to work with the FDA on trial plans by the middle of this year and could start its Phase 3 study in patients with F2 or F3-stage fibrosis as early as the third quarter of this year. A separate trial arm, in more severe F4 patients, would launch “very soon after that,” according to Zerhouni. That program will also include a subgroup analysis for patients who enter the study on a GLP-1 drug, a key feature that some other MASH biotechs have already incorporated into their trials. Akero found that the combination of its drug and GLP-1s made “substantial differences to the liver,” according to an exec in an earlier interview . Boston did not include a similar subgroup analysis in its Phase 2 study. For Kornowski, keeping up with competitors isn’t daunting. “I’m extremely motivated to do it well, and to do it fast,” she said.

临床2期并购临床结果

2025-01-30

·PRNewswire

Metabolic Dysfunction-Associated Steatohepatitis Market to Register Stunning Growth at a CAGR of 17.9% in the US by 2034 | DelveInsight

The MASH treatment landscape is evolving rapidly, driven by a diverse array of therapeutic classes, each with unique mechanisms and potential impacts. The forecast period reveals significant shifts and emerging trends that will shape future market dynamics. LAS VEGAS, Jan. 30, 2025 /PRNewswire/ -- DelveInsight's Metabolic Dysfunction-Associated Steatohepatitis Market Insights report includes a comprehensive understanding of current treatment practices, MASH emerging drugs, market share of individual therapies, and current and forecasted market size from 2020 to 2034, segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan]. Key Takeaways from the Metabolic Dysfunction-Associated Steatohepatitis Market Report According to DelveInsight's analysis, the market size for MASH was found to be USD 2.1 billion in the 7MM in 2023. In 2023, there were an estimated 42 million prevalent cases of MASH in the 7MM. Out of these, a total of ~15 million cases were diagnosed, and this number is projected to increase by the end of 2034 in the 7MM. Leading MASH companies such as Inventiva Pharma, Novo Nordisk A/S, Cirius Therapeutics, Akero Therapeutics, 89bio, Boehringer Ingelheim, Zealand Pharma, Galectin Therapeutics, Lipocine, Viking Therapeutics, Eli Lilly and Company, Boston Pharmaceuticals, Pfizer, HighTide Biopharma, CytoDyn, Merck & Co., Hanmi Pharmaceutical, Hepagene (Shanghai), Hepion Pharmaceuticals, Enyo Pharmaceuticals, Gilead Sciences, Poxel SA, Zydus Therapeutics, Sagimet Biosciences, Ionis Pharmaceuticals, Corcept Therapeutics, and others are developing novel MASH drugs that can be available in the MASH market in the coming years. The promising MASH therapies in the pipeline include Lanifibranor (IVA337), Semaglutide, Azemiglitazone (MSDC-0602K), Efruxifermin (EFX), BIO89-100 (Pegozafermin), Survodutide (BI 456906), GR-MD-02 (Belapectin), LPCN1144, VK2809, Tirzepatide, BOS-580, Ervogastat (PF-06865571) + Clesacostat (PF-05221304), HTD1801, Leronlimab (PRO 140), Efinopegdutide, HPG1860, Rencofilstat (CRV431), EYP001 (Vonafexor), Semaglutide/Cilofexor/Firsocostat, PXL065, Saroglitazar Magnesium, Denifanstat (TVB-2640), ION224, Miricorilant (CORT118335), and others. In March 2024, Madrigal Pharmaceuticals' groundbreaking product, REZDIFFRA (resmetirom), a once-daily, oral THR-ß agonist, received accelerated endorsement from the US FDA based on results from the Phase III MAESTRO-NASH trial. This approval marks a significant stride in the medical landscape, as REZDIFFRA becomes the inaugural and sole FDA-sanctioned therapy for adults afflicted with non-cirrhotic MASH, accompanied by moderate to advanced liver scarring (fibrosis) corresponding to stages F2–F3 fibrosis. Discover which therapies are expected to grab the major MASH market share @ Metabolic Dysfunction-Associated Steatohepatitis Market Report Metabolic Dysfunction-Associated Steatohepatitis Overview Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease that stems from metabolic dysfunction, often linked to obesity, diabetes, and other conditions of metabolic syndrome. MASH is characterized by the accumulation of fat in liver cells, accompanied by inflammation and liver cell injury, which can progress to fibrosis, cirrhosis, or even liver cancer. The primary drivers of MASH include insulin resistance, obesity, type 2 diabetes, and dyslipidemia. Genetic predisposition and a sedentary lifestyle also play significant roles. Environmental factors, such as a poor diet high in sugars and fats, exacerbate the condition. MASH is often asymptomatic in its early stages. When symptoms occur, they can include fatigue, vague abdominal discomfort, or pain in the upper right quadrant. In advanced stages, signs of liver dysfunction such as jaundice, swelling of the abdomen or legs, and confusion may arise. Diagnosis involves a combination of clinical history, physical examination, and diagnostic tests. Blood tests measuring liver enzymes (ALT, AST) often indicate liver inflammation. Imaging techniques like ultrasound, MRI, or FibroScan can identify liver fat and fibrosis. In some cases, a liver biopsy is required to confirm the diagnosis and assess disease severity. Metabolic Dysfunction-Associated Steatohepatitis Epidemiology Segmentation The MASH epidemiology section provides insights into the historical and current MASH patient pool and forecasted trends for the 7MM. It helps recognize the causes of current and forecasted patient trends by exploring numerous studies and views of key opinion leaders. The MASH market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Prevalent Cases of MASH Diagnosed Prevalent Cases of MASH Gender-specific Diagnosed Prevalent Cases of MASH Severity-specific Diagnosed Prevalent Cases of MASH Metabolic Dysfunction-Associated Steatohepatitis Treatment Market The approval of REZDIFFRA (resmetirom) in March 2024 represents a pivotal achievement in medical innovation, transforming the treatment landscape for MASH disease. This groundbreaking therapy addresses the root causes of MASH, offering renewed hope to patients grappling with this challenging condition. Clinical trials have shown impressive results, with REZDIFFRA effectively reducing symptoms like inflammation and fibrosis, enhancing liver function, and improving patients' quality of life. By providing healthcare professionals with a robust treatment option, this approval addresses a critical unmet need and has the potential to significantly alleviate the complications linked to advanced liver disease. The prevalence of MASLD is strongly linked to type 2 diabetes mellitus and obesity, particularly in individuals with a higher body mass index. However, MASLD occurrence is reduced in T2DM patients receiving treatments such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, GLP-1 receptor agonists, and insulin. Vitamin E, with its antioxidant properties, is regarded as a first-line pharmacological option for managing MASH, especially when dietary and lifestyle interventions are insufficient. Antifibrotic agents can help prevent the progression of liver fibrosis and MASLD into fibrotic MASH. The role of pioglitazone, an anti-diabetic medication, in improving MASH histology in T2DM patients is well-documented, but concerns remain regarding potential side effects like weight gain, fluid retention, cancer risk, and bone fractures. Additional therapeutic targets for MASLD and MASH include G protein-coupled receptors (GPCRs), estrogen-related receptor alpha (ERRα), bone morphogenetic proteins (BMPs), and KLFs. Bariatric surgery, or weight loss surgery, is the most effective intervention for treating obesity and diabetes, as it reduces food absorption while influencing gut hormone secretion and metabolic function. To know more about MASH treatment guidelines, visit @ Metabolic Dysfunction-Associated Steatohepatitis Management Metabolic Dysfunction-Associated Steatohepatitis Pipeline Therapies and Key Companies Lanifibranor (IVA337): Inventiva Pharma Semaglutide: Novo Nordisk A/S Azemiglitazone (MSDC-0602K): Cirius Therapeutics Efruxifermin (EFX): Akero Therapeutics BIO89-100 (Pegozafermin): 89bio Survodutide (BI 456906): Boehringer Ingelheim/Zealand Pharma GR-MD-02 (Belapectin): Galectin Therapeutics LPCN1144: Lipocine VK2809: Viking Therapeutics Tirzepatide: Eli Lilly and Company BOS-580: Boston Pharmaceuticals Ervogastat (PF-06865571) + Clesacostat (PF-05221304): Pfizer HTD1801: HighTide Biopharma Leronlimab (PRO 140): CytoDyn Efinopegdutide: Merck & Co./Hanmi Pharmaceutical HPG1860: Hepagene (Shanghai) Rencofilstat (CRV431): Hepion Pharmaceuticals EYP001 (Vonafexor): Enyo Pharmaceuticals Semaglutide/ Cilofexor/ Firsocostat: Gilead Sciences PXL065: Poxel SA Saroglitazar Magnesium: Zydus Therapeutics Denifanstat (TVB-2640): Sagimet Biosciences ION224: Ionis Pharmaceuticals Miricorilant (CORT118335): Corcept Therapeutics Discover more about MASH drugs in development @ Metabolic Dysfunction-Associated Steatohepatitis Clinical Trials Metabolic Dysfunction-Associated Steatohepatitis Market Dynamics The MASH market dynamics are expected to change in the coming years. Growing research activities and multiple clinical trials for MASH, driven by the rapid surge in its prevalence due to rising obesity and type 2 diabetes rates, highlight an active drug development pipeline and an expanding market size. The large pool of patients and lucrative growth opportunities present attractive prospects for key players, further supported by ongoing preclinical studies aimed at advancing imaging techniques for MASH diagnosis, potentially eliminating the need for invasive biopsy-based histopathological confirmation. Furthermore, potential therapies are being investigated for the treatment of MASH, and it is safe to predict that the treatment space will significantly impact the MASH market during the forecast period. Moreover, the anticipated introduction of emerging therapies with improved efficacy and a further improvement in the diagnosis rate are expected to drive the growth of the MASH market in the 7MM. However, several factors may impede the growth of the MASH market. Lack of awareness and negligence in the early stages of MASH by physicians often lead to disease progression, culminating in irreversible damage where liver transplantation becomes the only viable option. Diagnosing advanced MASH typically requires procedures like liver biopsy, which are costly, invasive, and risky. Regulatory challenges also pose hurdles, as the FDA mandates achieving one MASH endpoint for approval, while the EMA's draft guidance requires efficacy in both endpoints, potentially delaying first-mover approvals in major European markets. Additionally, access to expensive MASH treatments may be limited in certain regions, further hindering patient adoption. Moreover, MASH treatment poses a significant economic burden and disrupts patients' overall well-being and QOL. Furthermore, MASH market growth may be offset by failures and discontinuation of emerging therapies, unaffordable pricing, market access and reimbursement issues, and a shortage of healthcare specialists. In addition, the undiagnosed, unreported cases and the unawareness about the disease may also impact MASH market growth. Scope of the Metabolic Dysfunction-Associated Steatohepatitis Market Report Therapeutic Assessment: Metabolic Dysfunction-Associated Steatohepatitis current marketed and emerging therapies Metabolic Dysfunction-Associated Steatohepatitis Market Dynamics: Key Market Forecast Assumptions of Emerging Metabolic Dysfunction-Associated Steatohepatitis Drugs and Market Outlook Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, Metabolic Dysfunction-Associated Steatohepatitis Market Access and Reimbursement Download the report to understand which factors are driving MASH market trends @ Metabolic Dysfunction-Associated Steatohepatitis Market Trends Table of Contents Related Reports Non-Alcoholic Steatohepatitis Epidemiology Forecast Non-Alcoholic Steatohepatitis Epidemiology Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted NASH epidemiology in the 7MM, i.e., the United States, EU4 (Germany, France, Italy, Spain), the United Kingdom, and Japan. Nonalcoholic Steatohepatitis Pipeline Nonalcoholic Steatohepatitis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key nonalcoholic steatohepatitis companies, including Madrigal Pharmaceuticals, Intercept Pharmaceuticals, Cirius Therapeutics, Novo Nordisk, Inventiva, Galmed Pharmaceuticals, AstraZeneca, Galectin Therapeutics, Viking Therapeutics, Eli Lilly and Company, Terns Pharmaceuticals, Sinew Pharma, 89bio, Inc., Eccogene, Novartis Pharmaceuticals, Poxel SA, AngioLab, Pfizer, Arrowhead Pharma, LG Chem, Redx Pharma, Lipocine, Inc., CytoDyn, Inc., Alnylam Pharmaceuticals, Inc., Chemomab Therapeutics, NuSirt Biopharma, HK inno. N, Aligos Therapeutics, Altimmune, Inc., Kowa Pharmaceutical, Ionis Pharmaceuticals, NorthSea Therapeutics, Rivus Pharmaceuticals, Hanmi Pharmaceutical, Hepagene Therapeutics, HighTide Biopharma, Akero Therapeutics, Merck Sharp & Dohme LLC, Cascade Pharmaceuticals, Hepion Pharmaceuticals, Chipscreen Biosciences, Boston Pharmaceuticals, Bristol-Myers Squibb, Sunshine Lake Pharma, GSK plc., Future Medicine, Gilead Sciences, ENYO Pharma, Histogen, among others. Non-Alcoholic Fatty Liver Disease Market Non-Alcoholic Fatty Liver Disease Market Insight, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key NAFLD companies, including MediciNova, Eli Lilly and Company, AstraZeneca, Inventiva Pharma, Oasis Pharmaceuticals, LLC, Madrigal Pharmaceuticals, Inc., BioMarin Pharmaceutical, GlaxoSmithKline, Zydus Therapeutics Inc., Akero Therapeutics, Inc, Pfizer, Boehringer Ingelheim, Neuraly, Inc., Merck Sharp & Dohme LLC, Rivus Pharmaceuticals, Inc., Hepion Pharmaceuticals, Inc. , among others. Non-Alcoholic Fatty Liver Disease Pipeline Non-Alcoholic Fatty Liver Disease Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key NAFLD companies, including BeiGene, Inventiva Pharma, Cirius Therapeutics, Madrigal Pharma, Novo Nordisk, Galmed Pharmaceuticals, AstraZeneca, Galectin Therapeutics, Viking Therapeutics, Dr. Falk Pharma GmbH, Sagimet Biosciences, Eli Lilly and Company, Terns Pharmaceuticals, Sinew Pharma, Novartis Pharmaceuticals, Afimmune, Poxel SA, AngioLab, Pfizer, Oramed Pharmaceuticals, Can Fite Biopharma, MediciNova, Metacrine, Inc., Lipocine, Inc., CytoDyn, Inc., Alnylam Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma, Chemomab Therapeutics, NuSirt Biopharma, HK inno.N, Kowa Pharmaceutical, Ionis Pharmaceuticals, NorthSea Therapeutics, Rivus Pharmaceuticals, Hanmi Pharmaceutical, Hepagene Therapeutics, HighTide Biopharma, Akero Therapeutics, Enanta Pharmaceuticals, Cascade Pharmaceuticals, 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

临床3期

2024-11-16

·药明康德

每月一次！近70%患者达缓解，MASH疗法积极临床结果公布

▎药明康德内容团队编辑 Boston Pharmaceuticals今天宣布了一项2期试验的积极结果，该研究评估了每月一次的长效人类成纤维细胞生长因子21（FGF21）类似物efimosfermin alfa（BOS-580）对具有F2/F3期肝纤维化的代谢功能障碍相关脂肪性肝炎（MASH）患者的疗效与安全性。分析显示，BOS-580的治疗可显著改善肝纤维化≥1级，且MASH不会恶化，并且在24周内MASH缓解且肝纤维化不会恶化。详细数据将在美国肝病研究协会（AASLD）肝脏会议当中公布。根据此积极结果，该公司预计于2025年将临床项目推进到后期开发阶段。 MASH曾名为非酒精性脂肪性肝炎（NASH），是代谢功能障碍相关脂肪性肝病（MAFLD）的晚期形式。MASH是导致肝脏相关死亡的主要原因之一，对全球卫生系统造成日益加重的负担。此外，MASH患者，特别是那些具有更多代谢风险因素（高血压、合并2型糖尿病）的患者，心血管不良事件的风险增加，发病率和死亡率也相应提高。一旦MASH发展为显著的肝纤维化（F2和F3阶段），患者产生不良肝损伤结果的风险急剧上升。据统计，全球有超过2.5亿MASH患者，且预计到2030年，晚期患者数量将翻倍。研究显示，在超重或肥胖人群中，超过三分之一个体同时患有MASH。MASH患者在疾病早期通常症状不明显，甚至无明显症状，这常导致诊断延迟。与普通人群相比，MASH患者进展为晚期肝病（包括肝癌）的风险更高。这次所公布的试验是一项随机、双盲、安慰剂对照的2期研究（N=84），旨在评估试验24周，在活检确诊的F2或F3纤维化MASH患者中，每月一次皮下注射300毫克BOS-580的疗效和安全性。图片来源：123RF 关键疗效分析显示，45.2%的药物组患者在无MASH恶化的情况下获得≥1级的肝纤维化改善，而安慰剂组这一比例为20.6%（p=0.038）。有67.7%的药物组患者在无肝纤维化恶化的情况下实现MASH缓解，而安慰剂组这一比例为29.4%（p=0.002）。此外，38.7%的药物组患者实现MASH缓解并获得≥1级的肝纤维化改善，安慰剂组在此一数值上为17.6%（p=0.066）。接受BOS-580治疗的患者在研究期间表现出纤维化生物标志物的快速显著改善，肝损伤和肝脏脂肪的非侵入性标志物显著减少。患有2型糖尿病受试者的糖化血红蛋白（HbA1c）水平也有显著且具临床意义的改善。在24周的治疗期间，接受BOS-580治疗的患者因不良事件而停药的比率低，患者发生胃肠道副作用和注射部位反应的总体发生率亦低。 ▲试验疗效结果摘要（图片来源：参考资料[1]）目前BOS-580的2期临床开发计划正在继续进行，包括针对F2和F3患者的开放标签延长期研究，提供额外的24周治疗以评估长期安全性和疗效，并进一步验证BOS-580的低免疫原性。 BOS-580是一种每月一次皮下注射的长效人类FGF21变体，通过调节代谢通路来降低肝脂肪、改善肝损伤和炎症，并逆转MASH患者的肝纤维化。BOS-580在哺乳动物细胞中制造，具有类似人类的糖基化特性。目前该疗法正在开展针对MASH的2期临床试验。在早期的2a期12周临床研究中，BOS-580展现良好的安全性特征，并显示出在统计学上显著降低患者的肝脂肪含量、肝损伤标志物和纤维化标志物，同时改善患者的代谢生物标志物。 ▲在之前公布的2a期试验中，MASH患者在接受BOS-580治疗12周后在晚期脂肪肝纤维化代谢组学复合生物标志物上获得改善（图片来源：参考资料[2]） MASH疗法的开发是近年来产业关注的领域。今年3月，美国FDA加速批准Madrigal Pharmaceuticals药品Rezdiffra（resmetirom）联合饮食和运动，治疗患有中重度肝纤维化的MASH成人患者。根据新闻稿，这是获得FDA批准的首款MASH疗法，标志着该领域的一项重要里程碑。这个月初，诺和诺德（Novo Nordisk）宣布其减重疗法Wegovy（semaglutide，司美格鲁肽）在ESSENCE关键临床3期试验中，与安慰剂相比，可显著缓解MASH患者的肝纤维化并实现脂肪性肝炎消退。诺和诺德预计将于2025年上半年向美国和欧盟监管单位递交Wegovy用于治疗MASH的监管申请。Sagimet Biosciences则在今年10月宣布，其在研口服FASN小分子抑制剂denifanstat用于治疗MASH的临床2b期试验FASCINATE-2的结果发表于《柳叶刀》子刊The Lancet Gastroenterology & Hepatology。结果显示，denifanstat在疾病活动、MASH缓解和肝纤维化方面均实现了具有统计学显著性和临床意义的改善，支持这一疗法进入3期临床试验。同样专注于MASH的还有89bio公司。去年9月，其所开发的FGF21类似物pegozafermin用于治疗MASH的2b期试验结果登上《新英格兰医学杂志》，分析显示，有37%的15 mg pegozafermin治疗组患者的MASH得到缓解，此数值在安慰剂组仅有2%，该疗法用于治疗MASH的3期试验已经启动。而Akero Therapeutics的在研药品efruxifermin（EFX）用于治疗MASH的3期试验也已经开展。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] Boston Pharmaceuticals to Announce Positive Phase 2 Data on Efimosfermin Alfa (BOS-580) in F2/F3 MASH During Late-Breaking Oral Presentation at AASLD 2024, The Liver Meeting®. Retrieved November 15, 2024 from https://www.businesswire.com/news/home/20241115839453/en/Boston-Pharmaceuticals-to-Announce-Positive-Phase-2-Data-on-Efimosfermin-Alfa-BOS-580-in-F2F3-MASH-During-Late-Breaking-Oral-Presentation-at-AASLD-2024-The-Liver-Meeting%C2%AE [2] BOS-580, a long-acting FGF21 analogue, treatment shows beneficial changes in the circulating lipidome and improves MASEF score in patients with phenotypic metabolic dysfunction-associated steatohepatitis in a Phase 2a randomized, placebo-controlled, 12-week study. Retrieved November 15, 2024 from https://static1.squarespace.com/static/639a279aa2f7e15993210ea2/t/66e1d2827634e51ef9149505/1726075523483/WED-220+BOS-580+Part+A+Lipidomics+EASL+2024+Poster+5.9.24+Final.pdf 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床2期临床结果

100 项与 Efimosfermin alfa 相关的药物交易

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研发状态

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
非酒精性脂肪性肝炎	临床2期	美国	Boston Pharmaceuticals, Inc.初创企业	2021-09-30
肥胖	药物发现	美国	Novartis Pharmaceuticals Corp.	2018-02-26

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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


NCT04880031 (BOS-580-201, Biospace) 人工标引	临床2期	非酒精性脂肪性肝炎	84	Efimosfermin alfa 300 mg	醖淵選鹹鏇獵觸網築淵(構夢鏇艱齋網鹽繭鑰鏇) = 繭糧壓糧鏇齋廠築願築鬱遞夢獵廠餘齋襯廠淵 (醖壓蓋觸淵壓鑰鏇範簾 ) 更多	积极	2024-11-15
				Placebo	醖淵選鹹鏇獵觸網築淵(構夢鏇艱齋網鹽繭鑰鏇) = 糧遞醖鏇構蓋簾顧齋遞鬱遞夢獵廠餘齋襯廠淵 (醖壓蓋觸淵壓鑰鏇範簾 ) 更多
NASH_TAG2024	临床2期	-	102	BOS-580	(艱膚製廠鑰醖範範遞遞) = 製鹹淵糧簾憲淵構範齋願淵鏇遞蓋鹽齋餘衊夢 (鏇夢鬱襯構觸簾遞積衊 )	积极	2024-01-04
				Placebo	(艱膚製廠鑰醖範範遞遞) = 顧選製壓構蓋製鹽製鏇願淵鏇遞蓋鹽齋餘衊夢 (鏇夢鬱襯構觸簾遞積衊 )
NCT04880031 (Biospace) 人工标引	临床2期	非酒精性脂肪性肝炎	102	overall	(蓋鏇鏇鹹觸廠獵艱鹽醖) = No treatment emergent adverse events of hypoglycemia were reported in any patient enrolled in the study. 鑰壓願繭蓋齋獵鏇願鬱 (齋範選鏇鏇憲鏇網鬱醖 ) 更多	积极	2023-11-10
				BOS-580 (HbA1c≥6.5%)
NCT03466203 (Pubmed \| J Clin Endocrinol Metab)	临床1期	高甘油三酯血症 \| 肥胖	64	LLF580 300 mg	觸艱齋願鹹淵鏇餘積夢(鏇顧糧積鏇積構觸顧齋) = higher incidence of generally mild to moderate gastrointestinal adverse effects 衊製願淵遞蓋遞製齋糧 (艱繭獵製憲築鑰鬱獵鹽 )	-	2021-08-25