Investigational insights into the potential of angiotensin type II receptor agonists as therapeutics for idiopathic pulmonary fibrosis

Introduction: Current standard-of-care for idiopathic pulmonary fibrosis is limited to nintedanib and pirfenidone, which only slow the progressive loss of lung function and have significant adverse effects that are intolerable to many patients. There is therefore a significant unmet need for alternative treatments for this incurable disease.

Areas covered: This review describes emerging evidence implicating dysregulation of the renin-angiotensin system in IPF pathogenesis, and both pre-clinical and recent clinical data supporting activation of the anti-fibrotic AT₂R as a promising therapeutic strategy. The efficacy of AT₂R agonists across pre-clinical models of both IPF and relevant lung diseases is discussed, with a particular focus on favorable findings with the AT₂R agonist C21 (buloxibutid), leading to its current clinical trials for IPF.

Expert opinion: Rapid translation of C21 (now named buloxibutid), the first-in-class orally available AT₂R agonist, to early phase clinical trials for IPF have established its safety and disease-modifying potential. Ongoing development of novel, more highly selective AT₂R agonists may deliver the same clinical benefit as C21 with reduced off-target effects. The AT₂R drug class offers great promise as novel therapeutics, potentially extending beyond IPF to Other inflammatory and fibrotic lung diseases.

C21; Idiopathic pulmonary fibrosis; buloxibutid; fibrosis; inflammation; lung.