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From Slowing Decline to Restoring Function: Taladegib’s Promise in IPF, With Toby Maher, MD, PhD
Maher discussed taladegib's potential to improve FVC, rather than slow decline, in people with idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) remains one of the most challenging and devastating chronic lung diseases, marked by progressive scarring that relentlessly limits lung function and quality of life. For years, standard of care treatment with antifibrotic therapies like pirfenidone and nintedanib has focused on slowing but not halting the decline in lung capacity. Promising new data on taladegib (ENV-101), a hedgehog (Hh) inhibitor, show potential to disrupt that standard.
In a small phase 2a proof-of-concept trial recently published in The Lancet Respiratory Medicine and presented at the 2025 ERS International Congress, taladegib demonstrated an ability to improve rather than merely slow decline in lung function. Patients receiving the investigational therapy experienced measurable gains in forced vital capacity (FVC) and total lung capacity over 12 weeks, alongside reductions in CT-measured fibrosis. While the data are early and short term, they are an encouraging signal in a field where slowing disease progression has long been the most attainable goal. The phase 2a data support continued development in the ongoing phase 2b WHISTLE-PF trial, designed to confirm efficacy and long-term safety in a larger, global population.
HCPLive spoke with Toby Maher, MD, PhD, Professor of Medicine and Director of Interstitial Lung Disease at the Keck School of Medicine, University of Southern California, to learn more about the new data and about taladegib as the potenital first in a new class of therapy for IPF.
Maher gave some background on Hh signaling and other investigations into the pathway for IPF and other indications, including cancers. While earlier Hh inhibitors were limited by tolerability concerns, taladegib's more selective targeting yielded a favorable safety profile in the trial, supporting its use.
Maher shared his anticipation for further data that will come out of the WHISTLE-PF trial that he hopes will validate the initial findings. He also emphasized the importance of further research into the biology of IPF and earlier screening and detection of IPF to maximize therapeutic benefit.
"It's a small trial," Maher cautioned. "We never want to get too excited about small trials, but nonetheless, to actually see some improvement over [3 months] suggests that the efficacy of the drug is better than we've seen with other molecules in the past."
Maher's disclosures include Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, FibroGen, Genentech, GSK, Merck, PureTech Health, Sanofi, Trevi Therapeutics, and United Therapeutics.
