IPF, Hopes from a New Cure for the Disease That Takes Your Breath Away and Attacks Your Heart

At first, difficulty breathing appears after an effort. Then, progressively, dyspnea occurs even at rest. And then comes the cough , dry, difficult to control, with the fingers that can take on the classic “drumstick” shape. This can lead to respiratory failure with consequent suffering for the lungs and heart in those who suffer from idiopathic pulmonary fibrosis (or IPF, acronym for the English Idiopathic Pulmonary Fibrosis ). For those who suffer from this rare disease (incidence approximately 20/100,000 in males; 13/100,000 in women) but whose occurrence seems to be increasing, research offers important treatment prospects. This is demonstrated by the results of the Phase III FIBRONEER™-IPF and FIBRONEER™-ILD studies, which evaluated nerandomilast, an investigational oral drug that acts by inhibiting experimental phosphodiesterase 4B (PDE4B) in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), with and without background antifibrotic therapy, respectively.

The findings were published in the New England Journal of Medicine and presented as late-breaking data at the 2025 American Thoracic Society (ATS) International Conference.

What emerges from the research

Nerandomilast is an investigational drug that has not yet been approved for use. Its efficacy and safety have not yet been established. Both studies met the primary endpoint with both the 9 and 18 milligram doses, as assessed by the reduction in absolute change in forced vital capacity (FVC) from baseline to Week 52 compared to placebo. FVC is a measure of lung function.

“After several trials in the scientific community to advance new clinical data, IPF and PPF continue to have devastating consequences for patients,” said Toby Maher , MD, Ph.D., Professor of Clinical Medicine, Keck School of Medicine, USC Los Angeles. “Having two Phase III studies meet the primary endpoint is a major breakthrough for the scientific community, highlighting that nerandomilast could have a meaningful impact on unmet patient needs, both as monotherapy and in combination with current treatments.” Low rates of permanent treatment discontinuation were observed in both studies: in the FIBRONEER™--IPF study, adverse events led to permanent discontinuation of the study regimen in 14.0% of patients in the nerandomilast 18 milligram group, 11.7% of patients in the nerandomilast 9 milligram group, and 10.7% of patients in the placebo group. In the FIBRONEER™-ILD study, adverse events led to permanent discontinuation of the study regimen in 10% of patients in the nerandomilast 18 milligram group, 8.1% of patients in the nerandomilast 9 milligram group, and 10.2% of patients in the placebo group. In both studies, there were no imbalances between the nerandomilast and placebo groups with respect to adverse events of interest, such as vasculitis, depression or other conditions.

What are interstitial lung diseases and what is IPF?

The disease is part of the so-called "interstitial lung diseases" or "diffuse infiltrative pneumopathies". These are pathologies of the lung parenchyma (the part dedicated to gas exchanges between air and blood) characterized by improper accumulation of cells or extracellular substances in these areas. In practice, the opposite of what happens in emphysema (a disease that occurs due to the "disappearance" of lung tissue dedicated to gas exchanges).

This group includes a huge number of pathological entities whose cause may be known, may have a clear association with systemic diseases (the lungs represent only one - although sometimes the main - of the organs involved), entities in which a genetic mutation has been identified or finally they may be idiopathic (diseases whose cause is unknown).

All these conditions have in common functional alterations of the organ: reduction of the ability to mobilize air volumes during respiratory acts, therefore restrictive deficit, reduction of oxygen in the blood under stress or, in the most advanced stages, at rest. For many, the cure is known, for others there are drugs capable of interrupting the evolution towards respiratory failure; finally, in a smaller number of diseases, only treatments capable of reducing the functional decline are known or, when possible, it is necessary to resort to lung transplantation. Idiopathic pulmonary fibrosis is part of this last group.