Taladegib Improves Lung Fibrosis on Quantitative CT: Peter George, MBBS, PhD

A post hoc quantitative CT (QCT) analysis of the phase 2a ENV-IPF-101 trial found that taladegib (ENV-101), an oral hedgehog pathway inhibitor, increased lung volume and reduced imaging markers of interstitial lung disease (ILD) extent in patients with idiopathic pulmonary fibrosis (IPF), according to Peter George, MD, PhD, consultant respiratory physician and clinical lead for interstitial lung disease at Royal Brompton Hospital. George discussed the late-breaking abstract, presented at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain, held September 5 to 9, in an interview with HCPLive. George is also senior medical director for respiratory at Brainomix, the company whose e-Lung algorithm was used in this analysis.

The parent 12-week trial previously showed taladegib improved percent-predicted forced vital capacity (FVC) by a mean of 1.9% from baseline versus a 1.3% decline with placebo.1 In the new analysis, applying Brainomix's e-Lung algorithm to baseline and week-12 high-resolution CT scans from 34 patients (15 taladegib, 19 placebo), taladegib was associated with an increase in e-Lung volume compared with placebo (+204 mL vs −60 mL; P = .003) and a reduction in total disease extent, a measure of overall ILD burden (mean change, −2.9% vs +1.0%; P = .01).2 The taladegib group also showed a significant reduction in reticulovascular score, a marker of total fibrosis severity (−0.7% vs +0.5%; P = .04), a trend toward reduced weighted reticulovascular score (WRVS), a measure of peripheral fibrosis (−0.5% vs +0.6%; P = .1), and a significant reduction in pulmonary vascular volume (−0.35% vs +0.02%; P = .002).2

George said the taladegib and placebo groups were well matched at baseline, with WRVS of 15.5% and 14.2%, respectively, and that the taladegib group's slightly higher baseline severity, given that a WRVS above 15% has been linked in prior work to accelerated lung function decline, strengthens rather than undermines confidence in the findings. He also pointed to concordant signals between 2 independent QCT platforms, the UCLA Voyant algorithm used in the original analysis and Brainomix e-Lung used here, as evidence supporting a genuine drug effect rather than a technology-specific artifact.

George was direct about the disease being addressed. “IPF is a terrible disease. It's a disease that is associated with inexorable lung function decline, progressive symptoms, and certain death, and that is the reality of what is really a very severe disease,” he said.

He cautioned that this remains a small, post hoc analysis from a 12-week phase 2a trial, and that phase 2a signals have historically not always replicated in larger studies; he said the field awaits data from the ongoing phase 2b WHISTLE-PF trial before drawing firmer conclusions. Still, he said the combination of lung function and imaging signals adds confidence heading into that readout, and that quantitative CT could increasingly inform both trial go/no-go decisions and clinical treatment choices in IPF.

George’s disclosures include Boehringer Ingelheim, AstraZeneca, Daiichi Sankyo, Avalyn, and GSK, and he is senior medical director for respiratory at Brainomix.

References

1. Maher TM, Goldin JG, Hood J, et al. Taladegib for the treatment of idiopathic pulmonary fibrosis (ENV-IPF-101): a multicentre, randomised, double-blind, placebo-controlled, phase 2a trial. Lancet Respir Med. 2025;13(11):1001-1010. doi:10.1016/S2213-2600(25)00239-5

2. George P, Deveraj A, DiFrancesco A, et al. Treatment with taladegib results in increased lung volume and regression of markers of ILD: a phase 2a post hoc CT analysis using Brainomix e-Lung. Late-breaking abstract presented at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.