Taladegib Shows Potential to Improve FVC in Idiopathic Pulmonary Fibrosis

Taladegib was safe and demonstrated promising efficacy in a phase 2a trial in people with idiopathic pulmonary fibrosis (IPF).1

"Patients living with idiopathic pulmonary fibrosis face a relentless and life-altering disease that affects not only their health but every aspect of daily life," Toby M. Maher, MD, PhD, Professor of Medicine and Director of Interstitial Lung Disease at Keck School of Medicine, University of Southern California, Los Angeles, said in a statement.2 "We are encouraged by the totality of the clinical data for taladegib, as we observed not only significant improvements from baseline in forced vital capacity (FVC) measured by spirometry, but also a significant increase in total lung capacity and reductions from baseline in key measures of fibrosis as measured by CT imaging. These encouraging results, published in The Lancet Respiratory Medicine and presented today during the ERS ALERT session, represent meaningful progress toward the goal of delivering an effective treatment for patients living with IPF."

Taladegib, also known as ENV-101, is an Hh pathway inhibitor. New data validating the therapy are from the randomized, double-blind, placebo-controlled, phase 2a, proof-of-concept ENV-IPF-101 clinical trial. The trial was conducted at 16 clinical sites in Australia, Canada, Malaysia, Mexico, and South Korea and included patients with IPF older than 40 years who were not treated with concurrent IPF therapy. Patients were randomly assigned to receive taladegib 200 mg or placebo equivalent once daily, orally for 12 weeks, and were followed for 6 weeks. The trial primarily evaluated safety in the intention-to-treat population and change from baseline in FVC in the efficacy-evaluable population. Investigators also assessed exploratory outcomes including measures of fibrosis on high-resolution CT (HRCT) in the efficacy-evaluable population.

The trial evaluated 41 patients randomly assigned to the taladegib group (n = 21; 3 [14%] female and 18 [86%] male) or the placebo group (n = 20; 4 [20%] female and 16 [80%] male between Aug 12, 2021, and July 28, 2023. Maher and colleagues found that all treatment-emergent adverse events (AEs) possibly or probably related to the study drug were grade 1 or 2, mild or moderate in severity (except 1), and none were serious AEs. The most common treatment-emergent adverse events in the taladegib group were dysgeusia (n = 12; 57%) muscle spasms (n = 12; 57%), and alopecia (n = 11; 52%). These AEs were not reported in the placebo group, in which the most common AEs reported were diarrhea (n = 4; 20%), headache (n = 3; 15%), and dizziness (n = 1; 5%). There were no deaths during the trial.1

During the trial, taladegib showed potential for improving FVC, an unmet need that remains in the field despite the recent United States Food and Drug Administration (FDA) approval of nerandomilast 9 mg and 18 mg tablets (marketed as Jascayd; Boehringer Ingelheim), which was the first new approval in the IPF field in over 10 years. The approval was supported by nerandomilast’s ability to reduce FVC decline compared to placebo, as demonstrated in the phase 3 FIBRONEER-IPF trial.3

On the other hand, investigators in ENV-IPF-101 found that patients treated with taladegib had an improvement from baseline in FVC and across multiple HRCT-based measures of disease, although further research is still needed to confirm its potential benefits. Maher and colleagues found that between-group differences in change from baseline to week 12 favoured taladegib in percent predicted FVC (3·95% [95% CI ,0·31–7·60]; P = .035; mean change from baseline of 1.9% in the taladegib group vs –1·3% for placebo), total lung capacity by HRCT (257.0 mL [95% CI; 86.8–427.2]; P = .0040; mean change from baseline of 206·67 mL in the taladegib group vs –55·58 mL in the placebo group), and percent quantitative interstitial lung disease (P = .047; mean change from baseline of –9·4% in the taladegib group vs 1·1% in the placebo group).1

"We are honored that the results of our Phase 2a trial have been published in The Lancet Respiratory Medicine, one of the world’s most respected and top-tier medical journals, and also selected as an ALERT presentation at ERS. This recognition is a testament to the dedication of our scientific and clinical teams, the investigators, and most importantly, the patients who participated in the trial," John Hood, PhD, Co-Founder, CEO and Chairman, Endeavor BioMedicines, added.2 "Our team remains committed to advancing taladegib with our current Phase 2b WHISTLE-PF trial, which is on track and expected to be completed in 2026.”

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 Resp Med. Published online September 29, 2025.

2. Endeavor BioMedicines Announces Publication of Positive Data from Phase 2a Trial in The Lancet Respiratory Medicine Evaluating taladegib (ENV-101) in Individuals with Idiopathic Pulmonary Fibrosis. News release. Endeavor BioMedicines. September 30, 2025. https://finance.yahoo.com/news/endeavor-biomedicines-announces-publication-positive-063700806.html

3. Johnson V. Nerandomilast Nets First New FDA Approval for Idiopathic Pulmonary Fibrosis in Over 10 Years. HCPLive. Article. October 7, 2025. https://www.hcplive.com/view/nerandomilast-first-new-fda-approval-idiopathic-pulmonary-fibrosis-over-10-years