A randomized, double-blind, placebo-controlled phase 2b study was terminated due to adverse events (AEs) and a lack of efficacy of BG00011, an anti-αvβ6 immunoglobulin G1 monoclonal antibody, as therapy for idiopathic pulmonary fibrosis (IPF), according to a study published in the American Journal of Respiratory and Critical Care Medicine.

The study was carried out after a small phase 2a study established the ability of BG00011 to selectively target αvβ6-mediated transforming growth factor (TGF)-β activation and interrupt fibrogenesis.

“Based on the positive results in phase IIa, a phase IIb study was conducted to evaluate the efficacy and safety of BG00011 at a flat dose of 56 mg (approximately 0.7 mg/kg) compared with placebo in a larger population of patients with IPF who were either ‘on’ or ‘off’ background therapy with pirfenidone or nintedanib,” the authors explained.


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“The study was terminated early due to safety findings, as BG00011-treated patients generally fared worse than the placebo group, with a higher number of severe adverse events (SAEs), respiratory AEs, and IPF events.”

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The study included 106 patients with IPF from 16 countries, and it was initiated in September 2018 and terminated in August 2019. The participants were randomized to receive BG00011 or placebo. The study was terminated after a review by the Data Safety and Monitoring Board, which identified too many SAEs and a lack of clinical benefit to the patients.

Acute IPF exacerbations occurred approximately 4 months into the study, reflecting long-term toxicity associated with the treatment. None of the participants receiving placebo experienced acute IPF exacerbations, which led to the study’s early termination.

The authors suspect that the main problem with selective targeting of αvβ6-mediated TGF-β activation is the proinflammatory effect of the inhibition of TGF-β, which will need to be addressed in future investigations.

Reference

Raghu G, Mouded M, Chambers DC, et al. A phase IIb randomized study of an anti-αvβ6 monoclonal antibody in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Published online June 30, 2022. doi:10.1164/rccm.202112-2824OC