Depemokimab

LONDON, UK I September 09, 2024 I GSK plc (LSE/NYSE: GSK) today presented the full results from the SWIFT-1 and SWIFT-2 phase III clinical trials which assessed the efficacy and safety of depemokimab versus placebo in adults and adolescents with severe asthma with type 2 inflammation characterised by raised blood eosinophil count. 1 The data were presented at the European Respiratory Society International Conference (7-11 September) in Vienna, Austria and simultaneously published in the New England Journal of Medicine . SWIFT-1 and SWIFT-2 are duplicate studies with the same primary and secondary endpoints. Both trials met their primary endpoints with statistically significant reductions in the annualised rate of clinically significant exacerbations (asthma attacks) over 52 weeks versus placebo, with the pre-specified pooled analysis showing a significant 54% reduction in exacerbations [Rate Ratio 0.46, 95% CI, 0.36 – 0.59, p<0.001] (AER depemokimab = 0.51 exacerbations per year versus placebo = 1.11). 1 In the pooled analysis of SWIFT-1 and SWIFT-2, there was a 72% reduction [RR 0.28, 95% CI 0.13 – 0.61, p=0.002] (AER: depemokimab = 0.02 versus placebo = 0.09) in the secondary endpoint of clinically significant exacerbations requiring hospitalisation or emergency department visit compared to placebo. 1 As the pooled analysis of SWIFT-1 and SWIFT-2 did not control for multiple comparisons, results with a significant p-value (<0.05) are termed nominally significant. In the individual trials, the secondary endpoints assessing quality-of-life or the symptoms-based measure, showed improvements but did not reach statistical significance versus placebo. 1 These data are part of GSK’s aspirations to advance treatment goals for those with severe asthma. Preventing exacerbations, a known risk for hospitalisation, and cause of cumulative lung damage and disease progression, has been a longstanding goal of asthma treatment and care. 2 Sustained suppression of type 2 inflammation, an underlying driver of exacerbations, could help change the course of disease. 3 Extended dosing intervals could also help tackle other barriers to optimal outcomes such as adherence or frequent healthcare appointments. 4-7 Kaivan Khavandi, SVP, Global Head of Respiratory/Immunology R&D , said: “With a dosing schedule of just two injections per year, depemokimab has the potential to be the first approved ultra-long-acting biologic with six-month dosing. This could offer physicians and millions of patients with severe asthma an option that provides reassurance of sustained suppression of a key marker of type 2 inflammation and a reduction in the rate of exacerbations and hospitalisation – the fundamental treatment goal in asthma.” David Jackson, FRCP, MSc, PhD, lead author of SWIFT-1 and SWIFT-2, Professor of Respiratory Medicine at King’s College London and Clinical Lead for Severe Asthma at Guy’s and St Thomas’ Hospitals, London , said: “As a physician, it is encouraging to see results of research that could evolve the management of severe asthma. For me, preventing exacerbations and particularly those that lead to hospitalisations is a treatment priority for the people I see with severe asthma. Not only are exacerbations traumatic for patients, and contribute to pressures on healthcare systems/hospitals, but each exacerbation can cause irreversible changes to the tissue of the lungs that over time can lead to permanent loss of lung function and make a patient’s breathing progressively more difficult.” Depemokimab is the first ultra-long-acting biologic to be evaluated in phase III trials; it has high binding affinity and potency for interleukin-5 (IL-5), which will enable six-month dosing intervals for patients with severe asthma. 1 IL-5 is a key cytokine (protein) in type 2 inflammation, typically detected by raised blood eosinophil count. 1 More than 80% of people with severe asthma exhibit type 2 inflammation as the underlying pathobiology of their asthma. Identification of these people could guide physicians in initiating the right treatment for the individual’s type of asthma, thereby helping to reduce their risk of exacerbations. 3 The proportion of patients experiencing any adverse event (AE) was similar between the depemokimab and placebo group in SWIFT-1 (depemokimab = 73%, placebo = 73%) and SWIFT-2 (depemokimab = 72%, placebo = 78%). No deaths or serious AEs were determined to be related to the study treatment by the investigator. 1 The trial was conducted during a time of high COVID prevalence, and these events were recorded as the most common AE across groups. 1 There was no difference in reports of COVID between those receiving depemokimab or placebo in SWIFT-1 (depemokimab = 20%, placebo = 22%) and SWIFT-2 (15% for both depemokimab and placebo). 1 Nasopharyngitis, another name for the common cold, was the second most common AE in the pooled analysis. The proportion of patients experiencing a nasopharyngitis AE was lower in the depemokimab group than the placebo group in SWIFT-1 (depemokimab = 12%, placebo = 19%) and in SWIFT-2 (depemokimab = 13%, placebo = 21%). Safety analysis of the data continues as part of the open-label extension studies. 1 These data will inform regulatory filings around the world. Depemokimab is currently not approved anywhere in the world. About the depemokimab development programme The phase III programme consists of SWIFT-1 and SWIFT-2 in severe asthma, with an open label extension study (AGILE). 1,8 SWIFT-1 and SWIFT-2 were replicate 52-week, randomised, double-blind, placebo-controlled, parallel-group, multi-centre clinical trials. 1 The trials assessed the efficacy and safety of depemokimab adjunctive therapy in 382 and 380 participants who were randomised to receive depemokimab or a placebo respectively, in addition to their standard of care treatment with medium to high-dose inhaled corticosteroids plus at least one additional controller. 1 Number of subjects included in the Full Analysis of SWIFT-1: depemokimab = 250, placebo = 132 and in SWIFT-2: depemokimab = 252, placebo = 128. 1 The primary endpoint of reduction in the annualised rate of clinically significant exacerbations (asthma attacks) over 52 weeks vs. placebo for the individual studies were as follows: 1 An additional study (NIMBLE) is underway to assess the efficacy and safety of depemokimab when participants with severe asthma are switched from mepolizumab or benralizumab. 9 Depemokimab’s half-life and high potency for IL-5 means it has the potential to provide sustained inhibition of broad inflammatory functions and is being investigated in a variety of type 2 inflammatory conditions. 1,8-13 Depemokimab is currently being evaluated in phase III trials across a range of other IL-5 mediated diseases, including OCEAN for eosinophilic granulomatosis with polyangiitis (EGPA)10, ANCHOR 1 & 2 for chronic rhinosinusitis with nasal polyps (CRSwNP)11,12 and DESTINY for hypereosinophilic syndrome (HES). 13 About severe asthma and type 2 inflammation Severe asthma is defined as asthma that requires treatment with high-dose inhaled corticosteroids plus a second controller (and/or systemic corticosteroids) or biologic therapy, to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite treatment. 2 Estimates suggest that severe asthma accounts for more than 60% of all asthma-related costs in some countries, with higher per-patient costs than for a patient with type 2 diabetes or a stroke. 14 Patients with severe asthma bear a significant financial burden, for medical care and lost earnings. With some exacerbations leading to sick days or hospitalisation. 14 In more than 80% of patients with severe asthma, their condition is driven by type 2 inflammation in which patients exhibit elevated levels of eosinophils (a type of white blood cell). 3 Blood eosinophils count can be measured via a simple blood test. IL-5 is a core cytokine (protein) in type 2 inflammation alongside IL-4 and IL-13. 2 Type 2 inflammation drives the underlying pathology various immune-mediated conditions. IL-5 is responsible for the growth, activity, and survival of eosinophils. 2 About GSK in respiratory GSK is redefining the future of respiratory medicine as it builds on decades of pioneering work to deliver more ambitious treatment goals and develop the next-generation standard of care, for hundreds of millions of people with respiratory diseases. With an industry-leading respiratory portfolio and pipeline of vaccines, targeted biologics, and inhaled medicines, we are focused on improving outcomes and the lives of people living with all types of asthma and COPD along with less understood diseases like refractory chronic cough or rarer conditions like systemic sclerosis with interstitial lung disease. GSK is harnessing the latest science and technology with the aim to modify underlying disease dysfunction and prevent disease progression. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. References SOURCE: GlaxoSmithKline

注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需要得到授权。 1.恒瑞重磅Nectin-4 ADC「SHR-A2102」首次公布临床结果，疾病控制率 87.5%！ 2024 年 ESMO 大会摘要已公布，恒瑞首次公布了其 SHR-A2102（一种针对 Nectin-4 的 ADC）治疗晚期实体瘤患者的 I 期研究结果。数据显示，在接受过大量既往治疗的 NSCLC 患者中，ORR 为31.3%，DCR 为 87.5%。SHR-A2102为恒瑞医药自主研发且具有知识产权的靶向Nectin-4的抗体药物偶联物（ADC），其有效载荷是拓扑异构酶抑制剂（TOPi）。多种研究表明Nectin-4在肿瘤中的高表达与肿瘤的发展和不良预后密切相关。Nectin-4（基因名称PVRL4，脊髓灰质炎病毒受体4）蛋白是属于免疫球蛋白超家族的Nectin家族。Nectin家族与钙黏着蛋白共同作用，对粘着连接和紧密连接的产生和维持具有显著影响，它们调节多种细胞行为，包括细胞粘附、生长、分化、迁移和凋亡。Nectin-4蛋白在胚胎和胎盘中特异性表达，在少数正常成年组织（包括皮肤）中表达，以及在肿瘤组织中过表达。因此，探索靶向Nectin-4蛋白及联合治疗方案或可为晚期实体瘤患者提供更多的治疗选择。截至 2024年 4 月 9 日，共招募了 38 名患者（中位年龄：61 岁；≥3 线既往治疗：60.5%；既往接受过ICI 治疗：78.9%）。在剂量递增（D-ESC）期间，17 名患者接受 2 至 10 mg/kg 的 SHR-A2102 治疗。10 mg/kg 组中只有 1 名患者出现 DLT（4 级血小板计数减少），MTD 尚未达到。在剂量扩展（D-EXP）期间，另外 10 名和 11 名患者分别接受 6 mg/kg 和 8 mg/kg 的 SHR-A2102 治疗。数据显示，在 30 名可评估肿瘤反应的患者中，总的 ORR 为 23.3%，DCR 为 76.7%。在 16 名可评估的接受过大量既往治疗的 NSCLC 患者中，ORR 为 31.3%（非鳞癌，50.0%；鳞癌，12.5%），DCR 为87.5%（非鳞癌，75.0%；鳞癌，100.0%） 总体而言，42.1% (16/38) 的患者发生 3/4 级 TRAE，其中最常见(≥10%) 为白细胞计数减少 (21.1%)、贫血(18.4%)、中性粒细胞计数减少 (15.8%) 和淋巴细胞计数减少 (13.2%)。未发生与治疗相关的死亡。 2.国产首个！华东医药JAK抑制剂HDM3010启动Ⅲ期临床，治疗白癜风 9 月 9 日，药物临床试验登记与信息公示平台显示，华东医药在国内启动一项Ⅲ期临床，以评估 HDM3010 治疗白癜风患者的效果和安全性。HDM3010 是一款 JAK1/JAK2 抑制剂，是首个在国内启动白癜风 Ⅲ 期临床的国产 JAK 抑制剂。HDM3010首次申报临床在2023年10月获批，局部治疗12岁及以上成人和儿童患者的非节段性白癜风的I期临床已完成，2024年7月第二个适应症获批临床，用于18岁及以上轻中度结节性痒疹患者的局部治疗。本次启动的是一项随机、双盲 Ⅲ 期临床，研究的目的是评估 HDM3010 治疗中国白癜风患者的有效性和安全性。有效性的主要终点指标为：治疗第 24 周面部白癜风面积评分指数（F-VASI）较基线至少改善 75% 的受试者比例。全球范围内，目前仅有 Incyte 公司的 JAK 抑制剂芦可替尼乳膏（Opzelura）获批治疗白癜风。该药最早于 2022 年 7 月获 FDA 批准，用于 12 岁及以上非节段型白癜风患者的局部治疗。2023 年 4 月，该药再次获欧盟 EMA 批准，用于 12 岁及以上青少年及成人患者伴面部受累的非节段型白癜风的治疗。期待华东医药JAK抑制剂HDM3010 Ⅲ期临床能够进展顺利，早日获批。 3.百济神州PRMT5抑制剂BGB-58067片在国内申报临床，针对实体瘤 9月10日，中国国家药监局药品审评中心（CDE）官网公示，百济神州申报的1类新药BGB-58067片临床试验申请获得受理，这是该产品首次在中国申报临床。BGB-58067是一款PRMT5抑制剂，为百济神州实体瘤在研产品，预计于2024年进入临床研究阶段。PRMT的中文全称是蛋白质精氨酸甲基转移酶，它可催化靶蛋白上精氨酸残基的甲基化。根据文献，目前已发现了九个PRMT家族成员（PRMT1-9）。除PRMT8表达仅限于神经元外，其它PRMT成员一般在多种细胞和组织类型中以及跨物种中普遍表达。PRMT5是Skb1（粟酒裂殖酵母）和Hsl7（酿酒酵母）的人类同源物，起初在酵母双杂交筛选中作为Janus激酶2（JAK2）的结合蛋白被发现，因此早期被命名为JBP1。随后研究发现，该蛋白其实是精氨酸甲基转移酶，且对多种底物包括髓鞘碱性蛋白、纤维蛋白以及组蛋白H2A和H4等具有体外催化活性，因此研究人员才将其更名为PRMT5。已有研究发现，PRMT5可参与许多细胞活动，包括细胞生长、迁移和发育等。临床和临床前研究表明，PRMT5可在多种癌症中高表达，包括胃癌、肺癌、乳腺癌、结直肠癌、肺癌、淋巴瘤、膀胱癌、三阴性乳腺癌和髓系血液癌症等，其高表达会导致肿瘤细胞过度增殖，促进肿瘤生长。据不完全统计，当前全球范围内已有10多款PRMT5抑制剂进入到临床试验阶段，研发公司包括阿斯利康（AstraZeneca）、安进（Amgen）、百时美施贵宝（Bristol Myers Squibb）、强生（Johnson & Johnson）、石药集团等公司。 4.正大天晴PDE3/4抑制剂TQC3721吸入粉雾剂获批临床，针对慢性阻塞性肺病 9月9日，中国国家药监局药品审评中心（CDE）官网公示，正大天晴1类新药TQC3721吸入粉雾剂获批临床，拟开发用于慢性阻塞性肺病（COPD）患者的维持治疗。TQC3721是一款PDE3/4双重抑制剂。此前正大天晴开发了吸入用TQC3721混悬液剂型，目前正在中国开展治疗中重度COPD的2期临床研究。本次为吸入粉雾剂剂型首次在中国获批临床。COPD 是一种以气流受限为特点的常见呼吸系统疾病，患病率高、致残致死率高、病程且治疗周期长，其三个主要症状是呼吸困难、慢性咳嗽和咳痰。据世卫组织预计，COPD 将在2030 年成为全世界第三位主要死因；预计2060年会有超540万人死于COPD。PDE3调节气道平滑肌中的cAMP和cGMP，从而调节支气管张力；PDE4调节cAMP并参与炎症细胞活化和迁移，从而调节炎症反应和免疫细胞的活化。因此，抑制PDE3导致气道平滑肌松弛，抑制PDE4具有抗炎作用。研究显示，与单独抑制PDE3或PDE4相比，双重抑制PDE3和PDE4显示出在支气管扩张和抑制炎症反应两方面的协同或增强效应。今年8月，中国生物制药宣布该公司下属企业正大天晴已经完成TQC3721吸入性混悬液的1期和2期临床试验，并且2篇壁报全部被欧洲呼吸学会国际大会（ERS 2024）大会收录，其中一篇以最新重磅摘要（Late Breaking Abstract）的形式入选。这两项研究评估了TQC3721混悬液的安全性、耐受性、药代动力学特征和初步疗效，以及在中重度慢性阻塞性肺病患者中的有效性和安全性。 5.股票大涨16%！口服GLP-1R激动剂TERN-601减肥效果优秀，28天减重5% 9月9日，临床阶段的生物制药公司Terns Pharmaceuticals, Inc. (Nasdaq: TERN)公布，其口服GLP-1R激动剂TERN-601的Ⅰ期试验结果，结果显示，TERN-601的最高剂量组达到了4.9%的安慰剂调整平均体重减轻，患者每天接受一次TERN-601。公司还表示，这组67%的参与者减掉了5%或更多的基线体重。TERN-601是一种口服的小分子胰高血糖素样肽-1受体激动剂，或GLP-1R激动剂，是Terns内部发现的与肥胖相关的药物。TERN-601是利用Terns专有的受体三维QSAR模型，通过基于内部结构的药物发现工作而设计的。根据体外活性、代谢稳定性和药代动力学参数对配体进行了进一步优化。这一过程导致选择了TERN-601，一种倾向于cAMP生成的有效GLP-1R激动剂。1期试验是一项随机、双盲、安慰剂对照的单次和多次递增剂量(SAD和MAD)试验，在肥胖或超重的健康成人中评估TERN-601的安全性、耐受性、药代动力学(PK)和药效学(PD)。该试验的主要终点是评估TERN-601的安全性和耐受性，每天一次，持续28天。次要终点包括PK，用TERN-601治疗28天后体重减轻的疗效，以及其他探索性指标。 6.GSK超长效IL-5单抗depemokimab三期结果登《新英格兰医学杂志》，针对严重哮喘 9月10日，GSK公布了3期临床试验SWIFT-1和SWIFT-2的完整结果，这两项试验评估了在研单抗depemokimab与安慰剂相比，在具有2型炎症特征（以血液嗜酸性粒细胞计数为标志）的严重哮喘成人和青少年患者的疗效和安全性。分析显示，试验达主要终点，该疗法可显著降低患者哮喘发作率达54%。详细数据公布于欧洲呼吸学会国际会议（ERSIC）上，并同时发表在《新英格兰医学杂志》。depemokimab是一种具有超长半衰期的IL-5抗体，其设计允许患者每六个月接受一次注射。这种药物针对的是白细胞介素5（IL-5），这是一种在2型炎症反应中发挥核心作用的细胞因子。2型炎症通常通过嗜酸性粒细胞的增加来识别，是大多数严重哮喘患者的主要病理机制，可能导致病情的突然恶化。III期临床项目包括SWIFT-1和SWIFT-2两项研究，以及AGILE开放标签扩展研究。SWIFT-1和SWIFT-2是为期52周的随机、双盲、安慰剂对照、多中心临床试验，共纳入了755名参与者。这些参与者在接受标准治疗的同时，随机分配接受Depemokimab或安慰剂。分析显示，两项试验均达到了主要终点。即与安慰剂相比，该疗法在52周内显著降低患者临床显著恶化（哮喘发作）的年化率。预定的汇总分析显示恶化率显著降低达54%（HR=0.46，95% CI：0.36–0.59，p<0.001）。试验亦达成次要终点。与安慰剂相比，患者需要住院或急诊救治的临床显著恶化减少达72%（HR=0.28，95% CI：0.13–0.61，p=0.002）。在试验中，评估生活质量或患者症状指标的次要终点显示出改善，但与安慰剂相比未达到统计学显著性。 END 近期热门资源获取 后台回复关键词“报告”，获取数十篇药融云出品独家报告 后台回复关键词“2023首仿”，获取2023年首仿药物获批名单 后台回复“GLP-1深度报告”，获取完整《GLP-1产业现状与未来发展》PDF版。 后台回复“中国 I 类新药”，获取完整《中国 I 类新药靶点》PDF版。 后台回复“NAFLD/NASH”，获取完整《NAFLD/NASH报告》PDF版。 后台回复“AI+制药”，获取完整《中国AI制药企业白皮书》PDF版。 后台回复“XXG”，获取完整《中国心血管系统药物分析报告》PDF版。 后台回复“FZZJ”，获取完整《基于剂型改良的复杂注射剂分析》PDF版。 后台回复“药品进出口”，获取完整《中国药品进出口白皮书》深度报告-PDF版。 联系我们，体验药融云更多专业服务 会议 合作 园区 服务 数据库 咨询 定制 服务 媒体 合作 点击阅读原文，申请药融云企业版免费试用！