Constructive Knowledge for Nerandomilast in IPF/PPF

Boehringer Ingelheim revealed new information from two Section 3 scientific trials on Nerandomilast, an investigational orally-administered drug candidate for idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).

RT’s Three Key Takeaways:

• A brand new pooled evaluation of the FIBRONEER-IPF and FIBRONEER-ILD trials resulted in a nominally vital discount within the danger of demise by 59% in sufferers who obtained 18mg nerandomilast with out background remedy versus placebo.¹
• Each FIBRONEER part III trials, had met their main endpoint (discount of lung operate decline measured in pressured important capability) however didn’t meet their key secondary endpoint (danger of acute exacerbation, hospitalization for respiratory trigger, or demise).^1-3
• Nerandomilast had a positive security and tolerability profile, with the same charge of discontinuation resulting from hostile occasions as placebo.^1-3

Boehringer Ingelheim immediately introduced new information from the worldwide Section III FIBRONEER program on nerandomilast, an investigational oral preferential PDE4B inhibitor, which is at the moment not accepted to be used. The brand new pooled analyses, the primary to exhibit a nominally vital discount in danger of demise throughout IPF and PPF, was offered in a poster on the European Respiratory Society (ERS) Worldwide Congress 2025 in Amsterdam. Nominal significance implies that the trial outcomes confirmed a transparent pattern that implies a attainable profit; nevertheless, the proof doesn’t meet the strict standards to declare it statistically vital.

Nerandomilast (BI 1015550) is an investigational orally administered preferential inhibitor of phosphodiesterase 4B (PDE4B) that’s being studied as a possible remedy for IPF and PPF.^2,3 Its efficacy and security has not been established.

Nerandomilast was granted Breakthrough Remedy Designation by the US FDA for the remedy of IPF in February 2022 and for the remedy of PPF in April 2025.^7,8 

Idiopathic pulmonary fibrosis (IPF) is without doubt one of the extra widespread progressive fibrosing interstitial lung ailments (ILDs), primarily affecting folks over 50 and extra males than ladies.⁹ Sufferers with different sorts of fibrosing ILD may develop a progressive phenotype, termed progressive pulmonary fibrosis (PPF). PPF is outlined by worsening respiratory signs, physiological and radiological development, regardless of administration of the underlying trigger.¹² Globally, as much as 3.6 million folks could also be affected by IPF and as much as 5.6 million by PPF.^12,13

Section 3 Trials

In each FIBRONEER trials, sufferers (FIBRONEER-IPF, n=1177; FIBRONEER-ILD, n=1176) have been randomized to obtain nerandomilast 9mg twice per day, 18mg twice per day, or placebo.^2,3 The info was pooled and modifications in FVC over 76 weeks and clinically related outcomes (acute exacerbations, respiratory hospitalization, and demise) have been analyzed. The analyses included the general inhabitants and subgroups of sufferers by use of background remedy at baseline.¹

Within the general trial inhabitants, a nominally vital discount within the danger of demise by 43% was noticed in sufferers who obtained 18mg (HR 0.57 [CI: 0.41-0.78)].¹  A nominally vital discount within the danger of demise, by 59%, was noticed in sufferers who obtained 18mg nerandomilast with out background remedy (HR 0.41 [CI: 0.24-0.70)].¹ This downward pattern was additionally seen in sufferers taking background nintedanib with a nominally vital discount within the danger of demise by 41% (HR 0.59 [CI: 0.37-0.94)].¹

“For folks residing with pulmonary fibrosis, mortality stays unacceptably excessive, with each second individual dying inside 5 years of prognosis,” stated Shashank Deshpande, Chairman of the Board of Managing Administrators and Head of Human Pharma at Boehringer Ingelheim. “As the primary Section III trial program to exhibit a nominally vital discount within the danger of demise in progressive pulmonary fibrosis, FIBRONEER heralds a major advance for this group of sufferers, who face a devastating prognosis and really restricted remedy choices.”

Within the pooled evaluation, nerandomilast confirmed a positive security and tolerability profile, with the same charge of discontinuation resulting from hostile occasions as placebo, in step with the prior part III outcomes.¹ Essentially the most frequent hostile occasion within the nerandomilast group with out background remedy was diarrhea, reported in 14.6% within the placebo group, 17.5% within the nerandomilast 9 mg group, and 27.4% within the nerandomilast 18 mg group.¹ Sufferers receiving both background nintedanib or pirfenidone reported diarrhea in 27.1% within the placebo group, in 41.9% within the 9mg nerandomilast group and in 47.7% within the 18mg nerandomilast group. In all sufferers, severe hostile occasions occurred in 44.7%, 39%, and 40.5% of sufferers handled with placebo, nerandomilast 9 mg, and nerandomilast 18 mg, respectively.¹

Each part III trials, FIBRONEER-IPF and FIBRONEER-ILD, had met their main endpoint, demonstrating that nerandomilast slowed lung operate decline in IPF and PPF, with comparable discontinuation charges to placebo.^2,3 Though each trials didn’t meet the important thing secondary endpoint (time to first acute IPF/ILD exacerbation, first hospitalization for respiratory trigger, or demise over period of trial),^2,3 the pooled evaluation resulted in a nominally vital discount in danger of demise throughout IPF and PPF for the 18mg nerandomilast dose vs placebo in monotherapy and with background nintedanib¹ The pattern was extra pronounced in monotherapy.¹ 

“The brand new pooled information zoom in on nerandomilast’s potential as monotherapy, pairing efficacy with a nominally vital discount within the danger of demise.  Whereas the findings are exploratory, they add to the rising physique of proof and will influence future analysis instructions in pulmonary fibrosis,” stated Marlies Wijsenbeek, Erasmus MC College Medical Centre. “The brand new findings go hand-in-hand with nerandomilast’s favorable security and tolerability profile in earlier research. In a illness space with many sufferers discontinuing remedy,⁴ largely associated to restricted tolerability of present therapies, this might actually enhance outcomes for sufferers.”   

These newest FIBRONEER findings reinforce nerandomilast’s potential as a brand new remedy for IPF and PPF.¹

The FDA lately granted precedence assessment to the New Drug Utility (NDA) for nerandomilast in IPF, with an anticipated motion date in This fall 2025. An NDA for nerandomilast in PPF has additionally been filed. Regulatory submissions are underneath assessment in China, the UK, and the EU, with filings in different geographies to comply with.⁸

References

1. Oldham J, et al. (2025) Efficacy, security and tolerability of nerandomilast in sufferers with pulmonary fibrosis: pooled information from the FIBRONEER-IPF and FIBRONEER-ILD trials. Poster, ERS 2025.
2. Maher T et al. (2025) Nerandomilast in Sufferers with Progressive Pulmonary Fibrosis. N Engl J Med. 2025 Jun 12;392(22):2203-2214. DOI: 10.1056/NEJMoa2503643.
3. Richeldi L, et al. Nerandomilast in Sufferers with Idiopathic Pulmonary Fibrosis. N Engl J Med. 2025 Jun 12;392(22):2193-2202. DOI: 10.1056/NEJMoa2414108.
4. Levra S et al. Lengthy-term security of antifibrotic medicine in IPF: a real-world expertise. Biomedicines. 2022;10(12):3229. doi:10.3390/biomedicines10123229.
5. Zheng Q et al. The worldwide burden and temporal developments of interstitial lung illness: a scientific evaluation from the World Burden of Illness Research 2019. ERJ Open Res. 2022;8(1):00591-2021. DOI: 10.1183/23120541.00591‑2021.
6. Cen Z et al. Outcomes and predictors of development in progressive pulmonary fibrosis. Ann Med. 2024;56(1):2382949. DOI: 10.1080/07853890.2024.2406439.
7. Boehringer Ingelheim (2022) FDA Grants BI 1015550 Breakthrough Remedy Designation for Idiopathic Pulmonary Fibrosis. Accessed September 2025. Accessible at: 
8. Boehringer Ingelheim (2025) World part III trials exhibit that nerandomilast slowed lung operate decline in IPF and PPF, with comparable discontinuation charges to placebo. Accessed September 2025. Accessible at:   
9. European Lung Basis (2023) IPF – Idiopathic Pulmonary Fibrosis. Accessed April 2025. Accessible at: 
10. Siegel RL, Giaquinto AN, Jemal A. Most cancers statistics, 2024. CA: A Most cancers Journal for Clinicians. 2024;74(1):12–49. DOI: 10.3322/caac.21820.
11. Vancheri C, Failla M, Crimi N, et al. Idiopathic pulmonary fibrosis: a illness with similarities and hyperlinks to most cancers biology. Eur Respir J. 2010;35(3):496–504. DOI: 10.1183/09031936.00077309.
12. Cottin V, Teague R, Nicholson L, Langham S, Baldwin M. The Burden of Progressive-Fibrosing Interstitial Lung Illnesses. Entrance Med (Lausanne). 2022 Feb 1;9:799912. Doi: 10.3389/fmed.2022.799912. DOI: 10.3389/fmed.2022.799912.
13. Podolanczuk AJ et al. Idiopathic pulmonary fibrosis: cutting-edge for 2023. Eur Respir J. 2023;61(4):2200957. DOI: 10.1183/13993003.00957‑2022.