A New Hope on the Horizon: Nerandomilast
In the landscape of pulmonary fibrosis treatment, a significant development in 2025 is the investigational drug nerandomilast (BI 1015550). Developed by Boehringer Ingelheim, this oral medication has completed successful Phase 3 clinical trials and is currently undergoing review by the U.S. Food and Drug Administration (FDA). If approved, it would be the first new antifibrotic agent for interstitial lung disease (ILD) in over a decade.
How Nerandomilast works
Nerandomilast is a preferential inhibitor of phosphodiesterase 4B (PDE4B). The PDE4B enzyme is involved in the fibrotic process, which is the scarring of the lungs that characterizes pulmonary fibrosis. By inhibiting this enzyme, nerandomilast aims to interrupt the signaling pathways that lead to lung scarring. In preclinical studies, it has shown both antifibrotic and immunomodulatory effects, suggesting it can both slow fibrosis and modulate the immune response.
Promising Phase 3 trial results
The FIBRONEER clinical trial program demonstrated nerandomilast's effectiveness. The trials showed that nerandomilast significantly reduced the rate of decline in forced vital capacity (FVC)—a key measure of lung function—in patients with both idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). This was observed whether the drug was used as a monotherapy or in combination with existing antifibrotic agents, showing its versatility. The trial results also indicated a more favorable tolerability profile compared to currently approved treatments, with diarrhea being the most common side effect.
Potential impact and approval status
The positive trial results and favorable safety profile of nerandomilast offer fresh hope for patients who have difficulty tolerating the side effects of current medications. With a Priority Review designation from the FDA, a decision is expected in the fourth quarter of 2025. Approval would provide patients with a new, potentially better-tolerated treatment option and could also pave the way for combination therapies.
Other Innovative Therapies in the Pipeline
Beyond nerandomilast, the field of pulmonary fibrosis treatment is seeing a wave of innovation, including AI-driven drug discovery and repurposing existing medications.
AI-Designed Drugs: Rentosertib
Artificial intelligence has significantly accelerated the drug discovery process. Rentosertib, a TNIK inhibitor identified using AI, showed promising early results in a Phase 2a trial. The study found that IPF patients taking a specific dose of rentosertib had improved lung function compared to a placebo group. This represents one of the first AI-designed drugs to show potential for IPF treatment and highlights a faster, more cost-effective approach to finding new therapies.
Targeting Fibrosis Pathways: Taladegib, Buloxibutid, Admilparant
Several other investigational drugs are targeting different pathways involved in fibrosis:
- Taladegib (ENV-101): Granted Orphan Drug Designation by the FDA, this hedgehog pathway inhibitor is in Phase 2b trials.
- Buloxibutid: This AT2 receptor agonist received Fast Track designation and is in Phase 3 trials.
- Admilparant (BMS-986278): An LPA1 receptor antagonist, it is currently being investigated in Phase 3 clinical trials.
Repurposing Existing Medicines: Ipilimumab
Researchers at Tulane University have found that ipilimumab, an FDA-approved cancer drug, could potentially help treat IPF. By blocking a protein called CTLA-4, ipilimumab helps the immune system clear out the damaged, senescent cells that contribute to lung scarring. This approach may help restore lung function, though this is still in early research phases.
Comparison of Current and Emerging Therapies
The following table compares the current standard of care with key emerging therapies:
| Therapy | Mechanism of Action | Status | Efficacy Signal (FVC Decline) | Common Side Effects |
|---|---|---|---|---|
| Pirfenidone (Esbriet) | Antifibrotic and anti-inflammatory | FDA-Approved | Slows rate of decline | Nausea, rash, photosensitivity |
| Nintedanib (Ofev) | Tyrosine kinase inhibitor | FDA-Approved | Slows rate of decline | Diarrhea, nausea, liver issues |
| Nerandomilast | PDE4B inhibitor (oral) | Phase 3/FDA Review | Significantly slowed decline in trials | Diarrhea, generally well-tolerated |
| Rentosertib | TNIK inhibitor (AI-designed) | Phase 2a Positive | Increased FVC in 60mg dose group | Mild-moderate adverse events |
| Admilparant | LPA1 receptor antagonist | Phase 3 | Significant reduction in FVC decline | Trial data ongoing |
| Buloxibutid | AT2 receptor agonist | Phase 3 | Trial data ongoing | Trial data ongoing |
A New Approach to Managing Symptoms
In addition to the search for antifibrotic treatments, new drugs are being developed to manage the debilitating symptoms of pulmonary fibrosis. Chronic, persistent cough is a common and distressing symptom for many patients. Haduvio™ (oral nalbuphine ER) is an experimental therapy that showed significant promise in Phase 2a trials for treating chronic cough in IPF patients. By targeting the cough reflex, this medication offers a potential new avenue for improving quality of life for those with IPF.
The Path Forward for Pulmonary Fibrosis Treatment
While the current standard-of-care drugs, nintedanib and pirfenidone, have provided important options, they do not cure the disease and can have challenging side effects. The emergence of nerandomilast as a potential new therapy is a major step forward, offering improved tolerability and effectiveness as a monotherapy or combination treatment. The robust pipeline of other therapies, including AI-driven and repurposed drugs, further demonstrates that research is accelerating rapidly. The ongoing clinical trials provide hope for a future with more treatment options and improved quality of life for patients with pulmonary fibrosis. For up-to-date information on enrolling clinical trials, patients can consult their doctor or visit a trusted source like the Pulmonary Fibrosis Foundation's clinical trial finder.
Conclusion
The question of what is the new medicine for pulmonary fibrosis is seeing a hopeful answer with the advent of nerandomilast, an oral PDE4B inhibitor currently under FDA review. Its positive Phase 3 results suggest it may offer a more tolerable and effective treatment for both IPF and PPF than currently available options. Alongside this, AI-designed drugs like rentosertib and other innovative candidates targeting various fibrotic pathways are progressing through clinical trials, highlighting a significant leap forward in pharmacological research. As research continues to accelerate, the future holds promise for a broader range of medications to slow disease progression and manage symptoms more effectively, offering renewed hope to patients and clinicians alike.
