Benralizumab

After over a decade without notable progress in treating chronic obstructive pulmonary disease, patients with this ongoing condition now have two new treatment options, with more expected in the future. Regeneron and Sanofi recently revealed that the FDA has expanded the approved uses of their widely successful drug DUPIXENT to include COPD treatment. This marks the drug's sixth approved indication in the US, following its first approval seven years ago for atopic dermatitis. LAS VEGAS, Nov. 12, 2024 /PRNewswire/ -- Chronic obstructive pulmonary disease (COPD) is a progressive lung condition characterized by obstructed airflow, making breathing difficult. It primarily encompasses two main conditions: chronic bronchitis and emphysema, often coexisting. COPD typically develops due to long-term exposure to irritants such as cigarette smoke, air pollution, or occupational dust. As per DelveInsight analysis, the diagnosed prevalent population of COPD in the 7MM was around 44 million in 2023. These cases of COPD in the 7MM are expected to increase at a significant CAGR of 1.4% throughout the study period (2020–2034). As per the estimates, the majority of cases of COPD are in females as compared to males, in the US. But in EU4 and the UK, and Japan the diagnosed cases of males represent the majority of the cases. Overall, in the 7MM, females are predominantly high in number. In 2023, the US had around 3 million, 9 million, 5 million, and 1 million cases of GOLD 1, GOLD 2, GOLD 3, and GOLD 4, respectively based on the severity of airflow limitation. Estimates suggest that airflow limitation was higher in GOLD 2 severity. Various types of medications are used to manage COPD symptoms and complications, including bronchodilators, which help relax the muscles around the airways. This relaxation opens the airways and makes breathing easier. Most bronchodilators are administered via an inhaler. In more severe cases, the inhaler may also contain steroids to reduce inflammation. Some commonly used short-acting and long-acting bronchodilators for COPD management include Albuterol (ProAir HFA, Ventolin HFA, and others), Ipratropium (Atrovent HFA), Levalbuterol (Xopenex), Aclidinium (Tudorza Pressair), Arformoterol (Brovana), and Formoterol (Perforomist). In the LABA category, medications such as Striverdi Respimat, Arcapta/Onbrez, Serevent, and Brovana are included, while the LAMA class features drugs like Spiriva (available as Spiriva HandiHaler and Spiriva Respimat), Tudorza Pressair, Incruse Ellipta, Yupelri, Seebri Neohaler, and Lonhala Magnair. Since the generic version of Brovana was approved in April 2020, its market share has declined. Additionally, Arcapta Neohaler, Seebri Neohaler, and Utibron Neohaler were discontinued in the US in March 2020, which means they no longer contribute to market size. Patients who do not respond to single therapies are often prescribed double or triple therapy. Among the double therapies, the LABA+ICS combination is widely recommended, with drugs such as Symbicort, Breo Ellipta, and Advair. There are also LABA+LAMA combinations, including Anoro Ellipta, Stiolto Respimat, and Bevespi Aerosphere. In July 2020, the US FDA approved AstraZeneca's BREZTRI AEROSPHERE for the maintenance treatment of patients with COPD. Additionally, in October 2020, TRIXEO AEROSPHERE (a combination of formoterol fumarate, glycopyrronium bromide, and budesonide) received marketing authorization in the EU for the maintenance treatment of adult patients with moderate to severe COPD who are not adequately controlled by either a combination of an ICS and LABA or a LABA and LAMA. Currently, two triple combination therapies are available in the US: BREZTRI and TRELEGY ELLIPTA. Learn more about the FDA-approved COPD drugs @ Drugs for COPD Treatment Recently, Sanofi/Regeneron Pharmaceuticals' DUPIXENT added one more jewel to its crown by getting a label expansion nod for COPD from the FDA, EU, and NMPA. DUPIXENT's approval as the first targeted therapy for COPD represents a significant advancement in the treatment landscape for the disease. Unlike conventional treatments, which largely aim to manage symptoms, DUPIXENT specifically targets the IL-4 and IL-13 pathways linked to type 2 inflammation, a key driver in a subset of COPD patients. This precision in targeting allows for a more tailored treatment, especially for patients with elevated eosinophils, who often experience more frequent exacerbations and worse outcomes. The Phase III BOREAS trial demonstrated that patients treated with DUPIXENT experienced a 30% reduction in moderate-to-severe exacerbations over 52 weeks, significant improvements in lung function, and enhanced quality of life. By Week 52, those on DUPIXENT had improved prebronchodilator FEV1 by 160 mL compared to 77 mL in the placebo group. DUPIXENT was also well-tolerated, with a low frequency of adverse events. These results suggest that DUPIXENT could drastically shift COPD management by reducing exacerbations, improving lung function, and offering a safer, targeted therapy for patients with type 2 inflammation. To know more about COPD treatment options, visit @ New Treatment for COPD The chronic obstructive pulmonary disease pipeline possesses potential drugs in mid-stage developments to be launched in the near future. Itepekimab (Sanofi/Regeneron Pharmaceuticals), Benralizumab (AstraZeneca), Tezepelumab (Amgen/AstraZeneca), Mepolizumab (GSK), and others shall further create a positive impact on the market. Discover which therapies are expected to grab major COPD market share @ COPD Market Report Itepekimab is a fully human monoclonal antibody that targets interleukin-33 (IL-33), a protein involved in both type 1 and type 2 inflammation. The drug is administered via subcutaneous injection. Preclinical studies demonstrated that REGN3500 effectively inhibited several markers of both inflammatory types. Regeneron and Sanofi are investigating REGN3500 in diseases related to respiratory and dermatological inflammation. Currently, REGN3500 is in a Phase III clinical trial for COPD and was developed using Regeneron's VelocImmune technology, which produces optimized fully human antibodies. The development is part of a global collaboration between Regeneron and Sanofi. FASENRA (benralizumab) is a humanized recombinant monoclonal antibody of the IgG1k immunoglobulin type that selectively targets the alpha chain of the interleukin 5 receptor (IL-5R) found on eosinophils and basophils. It prevents IL-5 from binding and stops the hetero-oligomerization of the IL-5R's alpha and beta subunits, thereby inhibiting signal transduction. Additionally, it is an afucosylated IgG, which enhances its affinity for the FcγRIIIα receptor on natural killer cells, macrophages, and neutrophils. Approved by the FDA in November 2017 for severe eosinophilic asthma, benralizumab was developed by MedImmune, AstraZeneca's global biologics R&D division. The company is currently conducting Phase III clinical trials for FASENRA as a treatment for COPD. TEZSPIRE (tezepelumab), a pioneering human monoclonal antibody created by Amgen and AstraZeneca, has shown considerable therapeutic potential for various respiratory conditions. Originally intended for treating COPD, TEZSPIRE has yielded encouraging results in decreasing moderate-to-severe exacerbations in patients with high blood eosinophil counts. Recent findings from the Phase IIa COURSE Trial, unveiled at the ATS 2024 conference, underscored TEZSPIRE's effectiveness in minimizing COPD exacerbations among patients with different eosinophil levels. Mepolizumab is currently undergoing Phase III clinical trials for COPD, particularly in patients with frequent exacerbations and elevated eosinophil levels. It is available as an injectable solution and a powder for reconstitution for subcutaneous administration. The IL-5 receptor complex activates several signaling pathways that lead to the release of cytokines, neuromediators, chemokines, and various kinases, which facilitate eosinophil differentiation, proliferation, recruitment, and degranulation. Mepolizumab works by inhibiting the formation of the IL-5 receptor complex, thereby preventing eosinophil activation. This disruption affects normal eosinophil maturation and function, leading to decreased eosinophilic airway inflammation and reduced eosinophil survival. Discover more about drugs for COPD in development @ COPD Clinical Trials The anticipated launch of these emerging therapies for COPD 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 COPD market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for COPD in the 7MM is expected to grow from USD 16 billion in 2023 with a significant CAGR of 5% by 2034. This growth is mainly driven by the rise in the number of prevalent cases of COPD, ongoing clinical research, and better diagnostic tools that might improve the prognosis of the disease. DelveInsight's latest published market report titled as Chronic Obstructive Pulmonary Disease 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 COPD country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The COPD market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent Cases of COPD Subtype-specific Diagnosed Prevalent Cases of COPD Gender-specific Diagnosed Prevalent Cases of COPD Age-specific Diagnosed Prevalent Cases of COPD Diagnosed Prevalent Cases of COPD Based on Severity of Airflow Limitation Diagnosed Prevalent Cases of COPD Based on Symptoms and Exacerbation History The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM COPD market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this COPD 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 COPD market. Also, stay abreast of the mitigating factors to improve your market position in the COPD therapeutic space. Related Reports Chronic Obstructive Pulmonary Disease Pipeline Chronic Obstructive Pulmonary 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 COPD companies, including Sanofi, Chiesi Farmaceutici S.p.A., United Therapeutics Corporation, Verona Pharma plc, Immunotek, Yungjin Pharm. Co., Ltd., Pulmotect, Inc., Tetherex Pharmaceutical, CSL Behring, AstraZeneca, Novartis, Genentech, Vertex Pharmaceuticals, EmeraMed, Afimmune, Mereo BioPharma, Synairgen, Adamis Pharmaceuticals, Quercegen Pharmaceuticals LLC, Regend Therapeutics, Meridigen Biotech Co., Ltd., Pulmatrix, Eisai, GlaxoSmithKline, EpiEndo Pharmaceuticals, 3SBio, OmniSpirant, Foresee Pharmaceuticals, Amgen, Organicell Regenerative Medicine, Arrowhead Pharmaceuticals, ProterixBio, RS BioTherapeutics, MitoRx, C4X Discovery, Respiratorius, ARK biosciences, Incannex, GNI Pharma, Celon pharma, Alveolus Bio, Kinaset therapeutics, Landos Biopharma, Parion Sciences, KeyMed Biosciences, Bioneer corporation, AlgiPharma, Palobiofarma, Dimerix Bioscience, Glenmark Pharmaceuticals, among others. Asthma Market Asthma Market Insights, Epidemiology, and Market Forecast – 2034 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 asthma companies including GlaxoSmithKline, 4D Pharma plc, AstraZeneca, Suzhou Connect Biopharmaceuticals, Avillion, Pearl Therapeutics, ARS Pharmaceuticals, Sinomab, Avalo Therapeutics, Kymab, Sanofi, Cumberland Pharmaceuticals, Genentech, Inc. , among others. Asthma Pipeline Asthma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key asthma companies, including Jiangsu Hengrui Medicine, GlaxoSmithKline, Immunotek SL, AB Science, EMS, Avalo Therapeutics, Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd., ARS Pharmaceuticals, Sanofi, Zura Bio Ltd., AstraZeneca, EURRUS Biotech GmbH, T-Balance Therapeutics GmbH, Gossamer Bio, Aldeyra Therapeutics, Inc., Trio Medicines, Janssen Research & Development, Arrowhead Pharmaceuticals, Hoffman-La-Roche, GlaxoSmithKline, Biohaven Pharmaceutical, TAK-Circulator Co., Shanghai Hengrui Pharmaceutical, among others. Acute Respiratory Distress Syndrome Market Acute Respiratory Distress Syndrome Market Insights, Epidemiology, and Market Forecast – 2034 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 ARDS companies, including MediciNova, Edesa Biotech, Light Chain Biosciences, Boehringer Ingelheim, Genentech, Windtree Therapeutics, Biomarck Pharmaceuticals, Athersys, Healios, Direct Biologics, Biohaven Pharmaceutical, Arch Biopartners, APEPTICO Forschung und Entwicklung GmbH, Staidson (Beijing) Biopharmaceuticals, Veru, Mesoblast Limited, Avalo Therapeutics, Pluristem Therapeutics, ILTOO Pharma, 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

导读 重度哮喘是哮喘患者致残、致死的主要原因，具有高度的疾病未来风险，严重影响患者生活质量的同时，也造成了沉重的社会经济负担1。近年来，随着对哮喘发病机制认识的不断深入，以2型炎症通路相关细胞因子，如IL-5/IL-5R、IL-4、IL-13、IgE等为靶点的生物制剂不断推陈出新，为重度哮喘的治疗开辟了新的途径。 困境重重 我国重度哮喘现状不容乐观 根据GINA 2024，重度哮喘定义为在排除患者依从性及药物吸入技术因素外，规律联合吸入高剂量糖皮质激素（ICS）和长效β2受体激动剂（LABA）治疗3个月或以上，并在充分管理影响哮喘控制各种因素后，仍不能达到哮喘控制的患者，或上述治疗降级后失去控制的患者，这一定义下的重度哮喘约占哮喘患者的3.7%1。 具体到我国，据估计，成人哮喘患者有4570万，其中重度哮喘约占3.4%-8.3%，影响约394万人2，尽管其比例同全球范围内其他地区基本一致，但整体疾病控制情况与国外存在较大差距，是我国哮喘疾病负担的主要来源（图1）2-4： 图1 我国重度哮喘疾病负担沉重，现状不容乐观 哮喘治疗的长期目标是实现哮喘的长期控制，在重度哮喘的管理中，要实现这一目标，ICS/LABA的长期规范治疗是基本前提，也是临床广泛认为有效的治疗手段1,5。然而，由于重度哮喘主要由2型炎症驱动6，且该类型哮喘患者体内相关细胞因子（如IL-5、IL-13等）可能存在阈值效应——体现为随着患者体内T2炎症水平升高，细胞因子不断活化表达增加、升高至一定水平时，可能导致炎症细胞对激素的敏感性降低，因此，即使在高剂量激素治疗下，组织中炎症细胞仍存在持续增多的情况7-9。一项在重度哮喘患者中开展的前瞻性研究显示，即使接受了较高剂量的ICS/LABA+口服糖皮质激素（OCS）治疗，仍有74.5%的患者未实现哮喘控制10，且OCS的常见副作用还会进一步影响重度哮喘患者的健康和生活质量11,12。在此背景下，对于重度哮喘，寻找新的、有效及安全性良好的治疗方式一直是学术界所关注的热点。 借势而进 生物制剂已成破局之匙 支气管哮喘是一种包含多种临床表型的异质性气道疾病，这种异质性在临床、病理、生理等方面均有所体现（图2），并成为近10余年来哮喘领域新的研究热点，其中，炎症表型、分子表型等概念的提出和不断丰富完善，更是进一步深入阐明了哮喘的发病机制13。生物制剂亦在此背景下应运而生，通过靶向关键炎症通路实现精准治疗，为重度哮喘带来了新的希望。 图2 哮喘表型分类13 目前，我国已获批用于重度哮喘治疗的生物制剂主要包括本瑞利珠单抗、度普利尤单抗、美泊利珠单抗和奥马珠单抗四类，其作用靶点各异。对于重度哮喘患者，临床中可基于患者的临床表型选择相应的生物制剂进行精准治疗（图3）。 图3 国内已上市四种生物制剂机制及适用人群14-20 基于“精准靶向”的独特优势，上述生物制剂为不同表型重度哮喘患者带来了更多的治疗选择和更好的临床预后（图4），引领了重度哮喘新的治疗目标“临床缓解”的衍生21。 图4 生物制剂显著提高重度哮喘患者临床缓解比例 乘势而上 靶向上皮源性细胞因子新型生物制剂聚焦未及之需 成绩的获得不是结束，而恰恰是下一段探索的开始。 尽管现有生物制剂相较于传统治疗方案已取得诸多突破，但值得注意的是，我们仍需意识到，在重度哮喘领域，目前仍存在诸多挑战—— 识别重度哮喘分型的生物标志物检测受多种因素影响，需要动态监测 当前用以鉴别不同类型重度哮喘的生物标志物主要包括免疫球蛋白E（IgE）、嗜酸性粒细胞（EOS）和呼出一氧化氮（FeNO），但由于三种生物标志物可随时间动态变化，且部分检测结果受到多种因素影响（难以获取、其他疾病、既往用药等）（图5），因此临床中需动态监测，这无疑增加了检测的复杂性、成本和时间。 图5 重度哮喘生物标志物IgE、EOS和FeNO检测特点 约60%重度哮喘患者存在≥2种生物标志物升高，仅能针对单一生物标志物的各类现有生物制剂或作用有限 国际注册研究显示22，约60%的重度哮喘患者有≥2种生物标志物升高（图6）；我国C-BIOPRED研究亦显示2，多数重度哮喘患者同时存在血嗜酸性粒细胞（bEOS）和FeNO升高。 图6 国际注册研究中约60%的重度哮喘患者有≥2种生物标志物升高 现有生物制剂主要针对下游炎症通路，仅作用于T2型重度哮喘 当前市面上已有的生物制剂仅作用于T2型重度哮喘（图7），EOS数值较低的非T2型目前主要通过大环内酯类药物治疗、支气管热成型术等，选择有限且需综合考虑疗效与安全性问题23,24。 图7 现有生物制剂治疗靶点及适用重度哮喘类型 在此背景下，基于气道上皮在哮喘发病机制中的核心地位，近年来，靶向哮喘气道上皮源性细胞因子的新型生物制剂从级联反应顶部广泛抑制炎症，一方面可全面覆盖T2和非T2型哮喘，另一方面可同时靶向T2型炎症的多个驱动因素，影响几乎全部生物标志物，已成为重度哮喘治疗的重要研究方向，有望在解决上述挑战中取得突破。 重度哮喘是哮喘疾病负担的主要来源，生物靶向制剂的出现为患者带来了更多的治疗选择和更好的临床预后，并引领其治疗和管理迈向“临床缓解”的更高目标。期待随着更多新型生物制剂的不断发展和应用，未来重度哮喘的治疗将迎来更多的可能性和希望。 调研问题 参考文献： 1.GINA 2024. 2.Zhang Q, et al. Clin Transl Med. 2022;12(2):e710. 3.Zhang L, et al. Biomed Res Int. 2016;2016:9868704. 4.Yang X, et al. BMC Pulm Med. 2023;23(1):463. 5.中华医学会呼吸病学分会哮喘学组. 支气管哮喘防治指南（2020年版）. 中华结核和呼吸杂志，2020，43(12):1023-1048. 6.Deng Z, et al. Chin Med J (Engl). 2023 Jan 20;136(2):230-232. 7.Louis R, et al. Am J Respir Crit Care Med. 2000;161(1):9-16. 8.郭海琴，等. 临床肺科杂志. 2017; 22(10):1903-1909. 9.Dunican EM & Fahy JV. Eur Respir J. 2017;49:1701167. 10.Athanazio R, et al. BMC Pulm Med. 2016;16(1):153. 11.VOLMER T, et al . Eur Respir J. 2018 Oct 25;52(4):1800703, 12.Sweeney J et al. Thorax. 2016;71:339-346. 13.杜文,刘春涛.支气管哮喘的表型[J].中华临床免疫和变态反应杂志,2022,16(3):287-291. 14. Menzies-Gow A, et al. N Engl J Med. 2021 May 13;384(19):1800-1809.  15.Lai K, et al. Respir Med. 2024 Apr 1:107611. 16.Castro M, et al. N Engl J Med. 2018 Jun 28;378(26):2486-2496.  17.Chupp GL, et al. Lancet Respir Med. 2017;5(5):390-400. 18.Humbert M, et al.  Allergy. 2004;60:309-316. INNOVATE. 19.袁胜芳, 宋宁, 王布, 等.  成人重度支气管哮喘生物靶向治疗研究进展 [J] . 中华结核和呼吸杂志,2020,43 (04): 376-379. 20.中国医药教育协会慢性气道疾病专业委员会, 中国哮喘联盟. 重度哮喘诊断与处理中国专家共识（2024） [J] . 中华医学杂志, 2024, 104(20) : 1759-1789. 21.K. Milger-Kneidinger ,et al.Response to biologics and clinical remission in the adult GAN severe asthma cohort.ERS 2023. PA629 22.Denton E, et al. J Allergy Clin Immunol Pract 2021;9:2680–2688.e7 23.Bozzetto, et al, Curr Opin Pulm Med. 2015 Jan;21(1):16-21.  24.Anne M Fitzpatrick, et al. J Allergy Clin Immunol Pract. 2020 Feb; 8(2): 452-463. 本材料由阿斯利康提供，仅供医疗专业人士参考，不用于推广目的。 审批编号：CN-146310  有效期至：2025-11-4 -THE END- 医脉通是专业的在线医生平台，“感知世界医学脉搏，助力中国临床决策”是平台的使命。医脉通旗下拥有「临床指南」「用药参考」「医学文献王」「医知源」「e研通」「e脉播」等系列产品，全面满足医学工作者临床决策、获取新知及提升科研效率等方面的需求。