生物制剂在EGPA的首次面对面试验, comparing a single monthly injection of Fasenra to three injections per month of mepolizumab
Positive high-level results from the 曼达拉 Phase III trial showed 澳门葡京网赌游戏’s Fasenra (benralizumab) met the primary endpoint of the trial and demonstrated non-inferior rates of remission compared to mepolizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA) who were receiving oral corticosteroids (OCS) with or without stable immunosuppressive therapy.
曼达拉 is the first Phase III head-to-head trial of biologics in EGPA and compared the efficacy and safety of Fasenra versus mepolizumab, the only currently approved treatment.1,2 在盲法试验中, patients were randomised to receive either a single 30mg subcutaneous injection of Fasenra or three separate 100mg subcutaneous injections of mepolizumab once every four weeks.1,2
EGPA是一种罕见的, immune-mediated vasculitis that is caused by inflammation of small to medium-sized blood vessels.3,4 Approximately half of patients with EGPA have concomitant adult-onset severe eosinophilic asthma (SEA).5 EGPA会对多个器官造成损害, 包括肺, 皮肤, 心, 胃肠道和神经, which accumulates over time and without treatment can be fatal.3,6
Michael Wechsler博士, Principal Investigator said: “The positive 曼达拉 trial results are exciting because patients with eosinophilic granulomatosis with polyangiitis today have limited treatment options but face crippling symptoms, 如果不治疗甚至可能致命. This trial demonstrates that a biologic medicine given in a single monthly injection could help patients achieve remission rates comparable to the current standard of care, adding to the importance of benralizumab as a potential treatment option for eosinophilic granulomatosis with polyangiitis.”
Sharon Barr, Executive Vice President, 澳门葡京赌博游戏 R&D, 澳门葡京网赌游戏, said: “The positive results from 曼达拉 demonstrate that Fasenra, which has a unique mechanism of action and directly targets eosinophils, can help patients achieve remission from the debilitating impacts of this inflammatory disease with a more convenient single monthly subcutaneous injection.”
安全性和耐受性概况 Fasenra in the trial was consistent with the known profile of the medicine.
Full results from 曼达拉 will be presented at an upcoming medical meeting and data will be shared with health authorities around the world.
Fasenra is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of blood and tissue eosinophils in most patients via apoptosis (programmed cell death).7,8
Fasenra is currently approved as an add-on maintenance treatment for SEA in the US, EU, 日本和其他国家, and is approved for self-administration in the US, 欧盟和其他国家.9,10 FDA批准了孤儿药认定 Fasenra for EGPA in 2018 and 澳门葡京网赌游戏 continues to explore Fasenra的 除严重哮喘外的潜能, as a treatment across many diseases where eosinophils are expected to play a role.11-14
笔记
EGPA
EGPA, 以前被称为丘格-施特劳斯综合症, 是罕见的, immune-mediated inflammatory disease that is caused by inflammation of small to medium-sized blood vessels.3,4 It is estimated that 118,000 people throughout the world live with EGPA.15
EGPA会对多个器官造成损害, 包括肺, 皮肤, 心, 胃肠道和神经.3 The most common symptoms and signs include extreme fatigue, 减肥, 肌肉和关节疼痛, 皮疹, 神经疼痛, 鼻窦和鼻腔症状, 还有呼吸短促.3,6 如果不治疗，这种疾病可能是致命的.3,6
Elevated levels of eosinophils play a central role in EGPA disease pathophysiology.4 All patients with EGPA have very high levels of eosinophils at some point in their disease, both in peripheral blood and in affected tissues or organs.3,6 Approximately half of patients with EGPA have concomitant adult-onset SEA, 并且经常有鼻窦和鼻腔症状.3,5
EGPA的治疗选择有限. Patients are often treated with chronic high-dose OCS and can experience recurrent relapses when attempting to taper off OCS.6,16 Mepolizumab is currently the only approved treatment for EGPA.2
曼达拉
曼达拉是随机的, 双盲, double-dummy, active-控制, 平行组, 多中心 52-week Phase III trial which compared the efficacy and safety of Fasenra to mepolizumab in adult patients with relapsing or refractory EGPA.1 在盲法试验中, 140 patients were randomised 1:1 (70 per treatment group) to receive either a single 30mg subcutaneous injection of Fasenra or three separate 100mg subcutaneous injections of mepolizumab once every four weeks.1
The primary endpoint was the proportion of patients who were in remission at both weeks 36 and 48.1 Remission is defined as Birmingham Vasculitis Activity Score (BVAS)=0 and OCS dose less than or equal to 4mg/day.1 Fasenra remission was compared to the historical placebo rate from mepolizumab’s Phase III trial, MIRRA.17 The primary statistical analysis was to demonstrate non-inferiority of Fasenra 与mepolizumab相比基于主要终点.
All patients who complete the 52-week 双盲 treatment period may be eligible to continue into an open label extension (OLE) period, intended to allow each patient at least one year of treatment with 非盲 Fasenra.1
Mepolizumab is a humanized IL-5 antagonist monoclonal antibody.2
Fasenra
Fasenra (benralizumab) is currently approved as an add-on maintenance treatment for SEA in the US, EU, 日本和其他国家, and is approved for self-administration in the US, 欧盟和其他国家.9,10 Fasenra has been studied in almost 4,000 patients in global clinical trials.18-22
Fasenra is in 发展 for other eosinophilic diseases including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps and hypereosinophilic syndrome.12-14
Fasenra was developed by 澳门葡京网赌游戏 and is in-licensed from BioWa, Inc.是协和麒麟株式会社的全资子公司.有限公司.,日本.
呼吸 & 免疫学
呼吸 & 免疫学, 澳门葡京网赌游戏澳门葡京赌博游戏公司的一部分, is a key disease area and growth driver to the Company.
澳门葡京网赌游戏 is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, 常常使人衰弱的, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases.
澳门葡京网赌游戏
澳门葡京网赌游戏(LSE/STO/Nasdaq: AZN)是一家全球性制药公司, science-led biopharmaceutical company that focuses on the discovery, 发展, and commercialisation of prescription medicines in 肿瘤学, 罕见疾病, 和澳门葡京赌博游戏, 包括心血管, 肾 & 新陈代谢和呼吸 & 免疫学. 总部设在剑桥, UK, 澳门葡京网赌游戏 operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. 请访问 澳门葡京网赌游戏.com 并在社交媒体上关注公司 @澳门葡京网赌游戏.
参考文献
1. 临床试验.政府. Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab. (曼达拉). 可在:http://classic.临床试验.政府 / ct2 /显示/ NCT04157348. [最后访问日期:2023年9月].
2. Mepolizumab美国处方信息. 可从:http://www获得.accessdata.食品及药物管理局.政府/drugsat食品及药物管理局_docs/label/2023/125526Orig1s021,761122Orig1s011Corrected_lbl.pdf[最后访问日期:2023年9月].
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6. Baldini C，等. Clinical Manifestations and Treatment of Churg-Strauss Syndrome. Rheum Dis clinn Am. 2010;36:527–543.
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9. 澳门葡京网赌游戏新闻发布. 可在:http://www.AstraZeneca.com/media-centre/press-releases/2019/fasenra-approved-in-the-us-for-self-administration-in-a-new-pre-filled-auto-injector-the-fasenra-pen-04102019.html. [最后访问日期:2023年9月].
10. 澳门葡京网赌游戏新闻发布. 可在:http://www.AstraZeneca.com/media-centre/press-releases/2019/fasenra-receives-positive-eu-chmp-opinion-for-self-administration-and-the-new-fasenra-pen-a-pre-filled-single-use-auto-injector-01072019.html. [最后访问日期:2023年9月].
11. 澳门葡京网赌游戏新闻发布. 可在:http://www.AstraZeneca.com/media-centre/press-releases/2018/us-食品及药物管理局-grants-fasenra-orphan-drug-designation-for-eosinophilic-granulomatosis-with-polyangiitis-26112018.html. [最后访问日期:2023年9月].
12. 临床试验.政府. Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations (RESOLUTE). 可从:http://临床试验获得.政府 / ct2 /显示/ NCT04053634. [最后访问日期:2023年9月].
13. 临床试验.政府. Efficacy and Safety Study of Benralizumab in Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID). 可在:http://临床试验.政府 / ct2 /显示/ NCT04157335. [最后访问日期:2023年9月].
14. 临床试验.政府. A Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) (NATRON). 可从:http://临床试验获得.政府 / ct2 /显示/ NCT04191304. [最后访问日期:2023年9月].
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16. Bell CF等. Burden of illness and costs associated with eosinophilic granulomatosis with polyangiitis: evidence from a managed care database in the United States. J管理护理规范药房. 2021;27:1249-1259.
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18. Bleecker ER等. Efficacy and safety of benralizumab for patients with severe asthma 不受控制的 with high-dosage inhaled corticosteroids and long-acting β 2-agonists (SIROCCO): a randomised, 多中心, 安慰剂对照的3期试验. 《澳门葡京赌博游戏》. 2016;388:2115-2127.
19. 菲茨杰拉德JM等. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, 作为对重症患者的附加治疗, 不受控制的, 嗜酸性粒细胞哮喘(CALIMA):随机, 双盲, 安慰剂对照的3期试验. 《澳门葡京赌博游戏》. 2016;388:2128-2141.
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