SHR-1905

近日，ClinicalTrials.gov上新登记4项重磅III期临床试验，葛兰素史克（GSK）旗下在研新药Felcoreibart（GSK-5784283）开启了针对慢性阻塞性肺疾病（COPD）、哮喘两大慢性气道疾病的关键性临床开发征程，有望成为呼吸领域下一款潜力生物制剂。 关于Felcoreibart Felcoreibart是一款长效抗胸腺基质淋巴细胞生成素（TSLP）单克隆抗体，2023年8月，One Bio与江苏恒瑞医药达成独家协议，开发和商业化SHR-1905用于治疗哮喘和慢性鼻窦炎在全球范围内除大中华区外的地区，2024年GSK耗资10亿美元首付款收购Aiolos Bio（One Bio）获得Felcoreibart的大中华区外全部权益。 TSLP是气道炎症上游的核心调控因子，处于2型炎症反应的“源头位置”，能够启动并放大多条炎症通路，是哮喘、慢阻肺等慢性气道疾病非常热门的干预靶点。不同于已经上市的多款靶向下游IL‑5通路的生物制剂，阻断上游TSLP信号通路，理论上可覆盖更广的炎症人群，不受嗜酸性粒细胞水平限制，具备更大的适用潜力。 四项全新III期临床试验详情 本次一次性登记的4项试验统称为PERSIST项目，于2026‑08‑21/2026-08-24公示，全部为多中心、随机、双盲、安慰剂对照的III期研究，试验设计均采用「标准治疗基础上加用试验药物/安慰剂」的方案开展评估。 赛道格局：GSK加码气道疾病生物制剂版图 葛兰素史克长期深耕呼吸炎症赛道，已经拥有美泊利珠单抗（IL‑5单抗）、德莫奇单抗（IL‑5R单抗）等多款成熟的2型炎症生物制剂。但这类药物主要适用于嗜酸性粒细胞升高的患者群体，在非嗜酸性表型慢阻肺/哮喘患者当中疗效有限。 而Felcoreibart靶向炎症上游TSLP通路，如果III期临床顺利成功，有望突破现有生物制剂的人群局限，给更广谱的慢阻肺、难治性哮喘患者带来全新治疗选择，进一步巩固GSK在全球慢性气道疾病领域的管线优势。 小结 随着PERSIST系列III期试验正式启动，Felcoreibart已经走到了决定商业化前景的关键一步。未来3‑4年的临床结果，将会揭晓这款上游抗炎单抗能否给哮喘、慢阻肺治疗格局带来新的变革，后续我们也将持续跟踪该项目的临床进展。

GSK is looking to expand its COPD biologics franchise beyond IL-5 blockade, kicking off two Phase III studies of its long-acting anti-TSLP antibody felcorekibart (GSK5784283/AIO-001).Sanofi and Regeneron's IL-4/IL-13 inhibitor Dupixent (dupilumab) and GSK's IL-5 inhibitor Nucala (mepolizumab) are currently the only approved biologics for the condition.Earlier this year, CEO Luke Miels singled out felcorekibart as one of the pipeline programmes that could help GSK raise its game (see – Spotlight On: GSK's new CEO urges company to deliver 'more competitive products').The programme, acquired through GSK's 2024 takeout of Aiolos Bio for $1 billion upfront, will be tested in the PERSIST COPD-1 and PERSIST COPD-2 studies. Each will enrol 624 patients with moderate to very severe COPD to assess whether felcorekibart, added to standard therapy, can cut the annualised rate of moderate and severe exacerbations, according to ClinicalTrials.gov. Primary completion is targeted for mid 2029.GSK is also starting PERSIST ASTHMA-1, a 514-patient Phase III study of felcorekibart in patients with uncontrolled asthma. Three more late-stage studies of the drug are expected to begin this half as well (see – Vital Signs: GSK management comes out swinging with pipeline refresh).Tezspire and lunsekimig studiesThe COPD programme puts GSK in the race with other companies that are looking to make TSLP blockade a new treatment option against the respiratory disease. AstraZeneca and Amgen are testing the first approved TSLP-targeting drug Tezspire (tezepelumab) – it was originally cleared in 2021 for severe asthma followed by a label extension into chronic rhinosinusitis with nasal polyps last year – in the Phase III EMBARK and JOURNEY studies, each enrolling 990 patients with moderate to very severe COPD. Both trials are expected to report in early 2029.However, according to a recent FirstWord report, Tezspire's prospects as a potential therapy for patients with non-eosinophilic COPD were clouded following disappointing results from the Phase II COURSE study last year, which raised questions about the breadth of its potential benefit (see – KOL Views Q&A: Breadth of Tezspire's activity could be key asset in COPD battle with Dupixent). EMBARK and JOURNEY are evaluating Tezspire in a refined eosinophilic patient population."The initial thinking with tezepelumab was that because it targets early in the inflammatory cascade it may affect type 1 inflammation, which it does marginally. That makes it interesting, and so, certainly, I would like to see further development of it," one key opinion leader (KOL)  told FirstWord (see – KOL Insight: Chronic Obstructive Pulmonary Disease). "However, a lot of the Phase II COURSE study wasn't positive."Another said, "The last thing we need is another type 2 eosinophilic biologic in COPD. It's a disappointment because Tezspire could really help us with the non-eosinophilic patients, which are at least 70% of the [COPD] population."Meanwhile, Sanofi is pursuing a potentially differentiated TSLP strategy with lunsekimig, a bispecific antibody targeting both TSLP and IL-13. KOLs told FirstWord that honing and clearly defining the patient population responsive to lunsekimig – aiming for a niche distinct from Dupixent and Nucala – would be a strategy for success.The drug is currently being evaluated in the Phase IIb/III PERSEPHONE and THESEUS studies, each enrolling 942 patients with inadequately controlled COPD and an eosinophilic phenotype.