Idiopathic Pulmonary Fibrosis (IPF) remains one of the most challenging respiratory diseases to treat, characterized by progressive lung scarring and severely unpredictable disease progression. Despite high unmet clinical needs, the current standard of care—antifibrotic therapies nintedanib and pirfenidone—offers only modest benefits, with ongoing side effects that are a significant burden to patients. In our latest review, “Drug Discovery and Development in Idiopathic Pulmonary Fibrosis: The Changing Landscape“ published in Drug Discovery Today, we reflect on the state of IPF research, the recent clinical setbacks, and propose new strategies that could shape the future of IPF treatments. (For the next few weeks you can download a copy of the article without access restrictions here.)
Key Failures Drive Need for New Approaches
Our review outlines that since 2020, when our previous review on the topic was published, several high-profile IPF drug development efforts have failed in late-stage clinical trials—including autotaxin inhibitors, CTGF antibodies, pentraxin-2, and galectin-3 inhibitors. These failures have recast doubt on the viability of single-target therapies and have underscored the complexities inherent in IPF’s poorly understood etiology. The challenges are further compounded by the need for any new treatment to co-exist with the existing standard of care, which has proven a difficult balancing act due to adverse drug interactions.
Inhaled Therapies: A Promising Alternative
Among the most exciting developments highlighted in the article is the potential in shifting towards inhaled formulations, particularly of existing drugs like nintedanib and pirfenidone. Inhalation routes could offer localized efficacy in the lungs while reducing systemic side effects—marking a promising way forward in reducing gastrointestinal adverse events that have limited the broader success of oral treatments. Early results from clinical trials of inhaled formulations show promise in stabilizing lung function while mitigating the onerous side-effects linked to oral administration.
Breaking the Add-On Treatment Paradox
Combining new therapies with the current standard of care remains a critical hurdle. Our analysis reveals a paradox where, despite pre-clinical evidence suggesting that novel drugs paired with existing IPF therapies should improve patient outcomes, clinical experiences have largely shown the opposite—more frequent or severe side effects. We advocate for the integration of drug combination studies early in preclinical programs to fully assess the complexities of drug-drug interactions.
Conclusion: A Paradigm Shift is Needed
As we move toward the future, two distinct strategies appear promising: inhaled treatments and the exploration of polypharmacology—compounds that can act on multiple disease pathways rather than focusing on a single target. Also, the patent expiry of nintedanib in 2025 may signal a new era where innovative combination therapies can be evaluated in a more open landscape, but the focus must now be on optimizing both safety and efficacy for patients.
For a more in-depth look at the results of recent IPF trials and emerging strategies, we invite you to read our full article published in Drug Discovery Today. We believe the future of IPF treatment lies in rethinking existing paradigms and innovating beyond the current limitations.