GSK culls top respiratory disease prospect, delivering another blow to IL-33 field

GSK CSO Hal Barron
GSK Chief Scientific Officer Hal Barron, M.D. (GSK)

GlaxoSmithKline has culled (PDF) a phase 2 asthma drug it once identified as a top prospect for its faltering respiratory business. The decision to dump IL33r antagonist GSK3772847 follows lackluster clinical data on rival candidates against the same target.  

GSK secured the rights to GSK3772847 from Johnson & Johnson in 2016 in a deal worth up to £175 million ($227 million). At the time, GSK hailed the prevention of binding between IL-33 and the ST2 receptor as a way to treat a large proportion of severe asthmatics, reflecting evidence of the role the pathway plays in the regulation of inflammatory cells.

Regeneron and Sanofi dampened expectations for the class last year when their anti-IL-33 antibody REGN3500 performed numerically worse than Dupixent in a proof-of-concept asthma trial. Later in the year, they hammered home doubts about targeting IL-33 by failing a phase 2b atopic dermatitis study.

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GSK slipped out the news that GSK3772847 achieved proof of concept in the summer of 2019. Later, GSK presented results showing 67% of patients who received GSK3772847 intravenously every four weeks suffered loss of asthma control, compared to 81% of people on placebo.

At the time of its summer 2019 update, GSK said it would review the data before deciding on the next steps. A phase 2 trial in moderate to severe asthma patients with allergic fungal airway disease (AFAD) continued while GSK reviewed data from the other study. GSK stopped the AFAD trial in May having enrolled just 17 of the originally anticipated 46 participants. 

“Recruitment was terminated early before meeting target enrollment due to a high screen failure rate and the feasibility of completing the study in a timely way,” GSK wrote in its explanation for stopping the trial.

The cessation of the phase 2 and setbacks to other anti-IL-33 drugs pointed to the possibility of GSK killing off GSK3772847. Even so, the dumping of the candidate, which GSK attributed to “portfolio prioritization,” marks a swift decline for an asset GSK CEO Emma Walmsley singled out as a top respiratory disease prospect just two years ago. 

GSK’s pipeline of respiratory disease prospects, once a key area for the company, features phase 3 trials of approved drugs Nucala and Trelegy, plus a phase 1 study of  IL-5 antagonist GSK3511294. GSK is developing GSK3511294 as an asthma treatment. A PI4kβ inhibitor in development as a treatment for viral chronic obstructive pulmonary disease exacerbations, GSK3923868, entered (PDF) phase 1 in the latest update. GSK3772847 was the only drug to get the chop in the third-quarter review. 

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