Early data suggest a potential benefit of taladegib in idiopathic pulmonary fibrosis

The Hedgehog signalling pathway inhibitor taladegib, compared with placebo, led to a significant improvement in forced vital capacity (FVC) and other measures of lung fibrosis, while also increasing the rates of dysgeusia and muscle spasms in patients with idiopathic pulmonary fibrosis (IDP).

Dr Toby Maher (University of Southern California, CA, USA) presented results from ENV-IPF-101 (NCT04968574), a phase 2a, randomised, double-blind trial assessing oral taladegib 200 mg daily or placebo for 12 weeks. Participants were aged >40 years, diagnosed with IDP according to 2018 ATS/JRS/ERS/ALAT guidelines, with a predicted FVC >50% and a life expectancy of >12 months. The primary endpoint was safety, and a total of 41 participants were enrolled [1].

The most commonly reported adverse events (AEs) with taladegib compared with placebo included dysgeusia (57%), muscle spasms (57%), alopecia (52%), nausea (19%), and constipation (14%); none of these occurred with placebo. These AEs are typical among the class of Hedgehog inhibitor class. Following 12 weeks of treatment, the percentage predicted FVC increased by 1.9% from baseline with taladegib and decreased by 1.3% with placebo (P=0.035). Taladegib further led to improvements in radiographic measures of lung fibrosis, such as percentage quantitative interstitial lung disease, percentage qualitative ground glass, and percentage quantitative lung fibrosis.

“Treatment options are urgently needed for our patients with IDP, and this early phase 2a study of a Hedgehog inhibitor in IDP suggests the potential efficacy of this novel treatment approach,” concluded Dr Maher. “A phase 2b trial is now underway to evaluate these findings in a larger patient population.”

1. Maher T, et al. ENV-101 for the treatment of idiopathic pulmonary fibrosis: a randomised, double-blind, placebo-controlled phase 2 trial. ERS Congress, 27 September–1 October 2025, Amsterdam, the Netherlands.

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Posted on 30 October 202530 October 2025