Treatments for idiopathic pulmonary fibrosis are on the horizon
Article Date: 28 January 2026
Article URL: https://www.nature.com/articles/d41586-026-00109-7
Article Image: https://media.nature.com/w767/magazine-assets/d41586-026-00109-7/d41586-026-00109-7_51935830.jpg
Summary
Idiopathic pulmonary fibrosis (IPF) is a progressive, frequently fatal lung disease that often starts quietly and is diagnosed late. Existing standard therapies — nintedanib and pirfenidone — slow lung-function decline but have limited impact on mortality and cause burdensome side effects such as diarrhoea, which reduces uptake and tolerance.
New research points to clearer biological causes (genetic factors such as MUC5B variants and telomere-related mutations, plus environmental triggers) and a shift in drug development toward targeting earlier steps in disease, and improving tolerability. Several candidates are in trials: some target TGF-β signalling more precisely (for example, GTX-11 and rentosertib), others block profibrotic lipids or receptors (admilparant), and some aim to promote epithelial repair (buloxibutid).
Not all approaches have succeeded: integrin inhibitors (for example bexotegrast) and some autotaxin inhibitors produced adverse outcomes in trials, highlighting the narrow therapeutic window and biological redundancy. The notable recent advance is the FDA approval of nerandomilast (October 2025) after a phase III trial showed it slowed lung-function decline by more than one-third over a year and was much better tolerated than older drugs. Researchers now aim to detect disease earlier and combine treatments that both prevent fibrosis and promote repair.
Key Points
- IPF is usually diagnosed late; untreated, it commonly causes respiratory failure within 3–5 years.
- Current standard drugs (nintedanib and pirfenidone) slow decline in forced vital capacity (FVC) but have limited mortality benefit and significant side effects.
- Genetic factors (MUC5B, TERT/TERC and surfactant-gene mutations) and environmental exposures contribute to disease onset and progression.
- Targeting TGF-β and related pathways is biologically plausible but challenging; some approaches (integrin inhibitors) caused harm in trials.
- New agents show promise: nerandomilast has FDA approval (Oct 2025) after phase III data showing reduced FVC decline and markedly improved tolerability.
- Admilparant (LPA-receptor blocker) showed positive phase II results without common gastrointestinal side effects and is proceeding to phase III.
- Strategies that promote epithelial repair (for example buloxibutid) aim to stop IPF early rather than only limit fibrosis.
- A combination, multi-target approach and earlier detection of disease are likely to be needed to transform outcomes.
Why should I read this?
Quick take — it’s actually good news. For years IPF looked grim: slow drugs, nasty side effects, poor uptake. Now we’ve got a genuinely better-tolerated drug approved, sensible new targets in the pipeline, and a move towards treating disease earlier and repairing lungs rather than only slowing scarring. If you care about lung health, drug development or clinical practice, this piece flags the drugs and pathways to watch.
Context and relevance
This article matters because it captures a turning point in IPF research: a clearer understanding of genetic and environmental drivers, a recognition that late-stage anti-fibrotic strategies have limits, and a pipeline shift towards earlier intervention and repair. The approval of nerandomilast and promising mid-stage data for agents such as admilparant and rentosertib could change clinical practice, improve tolerability for patients, and make recruitment into early-disease trials feasible. However, past trial failures show the field must balance efficacy against risk of acute lung injury — combination therapies and better diagnostics will be key.