2014年10月21日讯 /生物谷BIOON/ --业界认为，用于哮喘治疗时，单抗dupilumab将成为改变游戏规则的新药。dupilumab对多种炎症性疾病均具有治疗潜力。目前，赛诺菲正调查dupilumab用于哮喘、特应性皮炎（AD）、慢性鼻窦炎的治疗。
赛诺菲（Sanofi）和合作伙伴Regeneron近日宣布，启动单抗药物dupilumab III期临床项目LIBERTY AD，将调查dupilumab治疗特应性皮炎（atopic dermatitis，AD）的疗效和安全性。该项目将由至少5个III期临床试验组成，首个III期研究（LIBERTY AD CHRONOS）将招募700例中度至重度特应性皮炎（AD）成人患者，主要终点是调查dupilumab结合外用皮质类固醇治疗中度至重度特应性皮炎（AD）的疗效（16周），次要终点是评估dupilumab的长期安全性及有效性（52周）。
此前，在4项II期临床试验中，dupilumab快速且显著减少了特应性皮炎（AD）成人患者的皮肤损伤和瘙痒，目前，该病现有的治疗选择疗效十分有限。赛诺菲最初开发dupilumab用于哮喘的治疗，而这些结果表明，dupilumab潜在获益人群将从哮喘扩大至第二种特异性疾病，并还可能使其他特异性疾病患者受益。
特应性皮炎（AD）是一种慢性、复发性炎症性皮肤病，主要表现为剧烈的瘙痒、明显的湿疹样变和皮肤干燥。特应性皮炎（AD）常常自婴幼儿发病，部分患者延续终生，可因慢性复发性湿疹样皮疹、严重瘙痒、睡眠缺失、饮食限制以及心理社会影响而严重影响患者的生活质量。
目前，赛诺菲和Regeneron也正在调查dupilumab对哮喘和慢性鼻窦炎的治疗。在一项IIa期临床试验中，dupilumab消减了87%的哮喘发作，该数据是近20年中在哮喘临床试验中所取得的最激动人心的数据。对于中度至重度过敏性哮喘群体而言，dupilumab有望成为一个改变游戏规则的药物。目前哮喘的治疗一直是类似于创可贴疗法，这些疗法没有攻击到疾病的根本原因，而dupilumab可能能够解决疾病根源问题。
Dupilumab是一种全人源化单克隆抗体，靶向白介素4受体(IL-4R)的α亚基，由Regeneron公司利用其开创性的Veloclmmune技术开发，目前该公司正与赛诺菲合作开发dupilumab。
通过阻断IL-4Rα亚基，dupilumab能够调节II型辅助T细胞（Th2）免疫应答中2种驱动因子——白介素-13(IL-13)和白介素-4（IL-4）的信号通路，这2种细胞炎性因子是参与炎症反应的关键蛋白。
英文原文：Sanofi, Regeneron start Phase 3 trial of dupilumab in eczema
Sanofi and Regeneron Announce Start of Phase 3 Study of Dupilumab in Patients with Atopic Dermatitis
TARRYTOWN, N.Y. and PARIS, October 20, 2014 - Sanofi and Regeneron Pharmaceuticals, Inc. today announced that the first patients have been dosed in a Phase 3 clinical study of dupilumab, an investigational therapy that blocks IL-4 and IL-13 signaling, in adults with moderate-to-severe atopic dermatitis (AD) that is not adequately controlled with topical AD medications.
LIBERTY AD CHRONOS, the first trial in the Phase 3 clinical program for dupilumab, is a randomized, double-blind, placebo-controlled, multi-national study with the primary objective of demonstrating the efficacy of dupilumab in adults with moderate to severe AD when administered concomitantly with topical corticosteroids through 16 weeks. Secondary objectives of the study will evaluate the long-term safety and efficacy of dupilumab up to 52 weeks. The trial will enroll approximately 700 adult patients.
"Moderate-to-severe atopic dermatitis is a serious disease characterized by severe itching, sleep disturbances and widespread rash, and existing treatment options have limited efficacy," said Donald Y. M. Leung, MD, PhD, a member of the LIBERTY AD Clinical Trials Steering Committee and Head of the Division of Pediatric Allergy and Immunology at National Jewish Health in Denver, CO. "This Phase 3 program will evaluate if blocking IL-4 and IL-13, two key cytokines in the Th2 inflammatory pathway, may provide a potential new approach for this chronic, difficult-to-manage disease."
The LIBERTY AD Phase 3 clinical program will consist of at least five trials of patients with moderate-to-severe AD at sites worldwide. For more information on the LIBERTY AD CHRONOS study, please visit: http://clinicaltrials.gov/ct2/show/NCT02260986?term=dupilumab&phase=2&rank=2.
About the IL-4/IL-13 Pathway and Atopic Dermatitis
Moderate-to-severe atopic dermatitis, a serious, chronic form of eczema, is a systemic inflammatory disease characterized by an allergic response driven by a subset of immune cells called Type 2 helper T cells, or Th2 cells. IL-4 and IL-13 are key cytokines that are required for the initiation and maintenance of this Th2 immune response.
Moderate-to-severe forms of atopic dermatitis can be characterized by pronounced pruritus (itch), cutaneous dryness, and skin lesions marked by redness, infiltration/papulation, crusting/oozing, and lichenification (skin thickening), with periods of lesion exacerbation. Intense itching, scratching, and skin damage can lead to secondary infections. Atopic dermatitis is often associated with other inflammatory disorders such as asthma.[1] Moderate-to-severe atopic dermatitis can negatively impact patients' lives and is associated with a high burden to society in terms of direct costs of medical care and prescription drugs and loss of productivity. [2],[3],[4],[5]
About Dupilumab
Dupilumab, a fully-human monoclonal antibody, is directed against the IL-4 receptor alpha subunit, which blocks signaling from both IL-4 and IL-13. Dupilumab was created using Regeneron's pioneering VelocImmune® technology and is being co- developed with Sanofi in atopic dermatitis, asthma and chronic sinusitis with nasal polyposis. Dupilumab is an investigational agent under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority.