SHR-1905

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.