Nerandomilast

A new pooled analysis of the FIBRONEER™-IPF and FIBRONEER™-ILD trials resulted in a nominally significant reduction in the risk of death by 59% in patients who received 18mg nerandomilast without background therapy versus placebo.1 Both FIBRONEER™ phase III trials, had met their primary endpoint (reduction of lung function decline measured in forced vital capacity) but did not meet their key secondary endpoint (risk of acute exacerbation, hospitalization for respiratory cause, or death).1-3 Nerandomilast had a favorable safety and tolerability profile, with a similar rate of discontinuation due to adverse events as placebo.1-3 Findings presented at ERS support previous clinical trial data on the safety and efficacy of nerandomilast in IPF and PPF as monotherapy and in combination with currently approved medications.1 Boehringer Ingelheim today announced new data from the global Phase III FIBRONEER™ program on nerandomilast, an investigational oral preferential PDE4B inhibitor, which is currently not approved for use. The new pooled analyses, the first to demonstrate a nominally significant reduction in risk of death across IPF and PPF, was presented in a poster at the European Respiratory Society (ERS) International Congress 2025 in Amsterdam. Nominal significance means that the trial results showed a clear trend that suggests a possible benefit; however, the evidence does not meet the strict criteria to declare it statistically significant. Both phase III trials, FIBRONEER™-IPF and FIBRONEER™-ILD, had met their primary endpoint, demonstrating that nerandomilast slowed lung function decline in IPF and PPF, with similar discontinuation rates to placebo.2,3 Although both trials did not meet the key secondary endpoint (time to first acute IPF/ILD exacerbation, first hospitalization for respiratory cause, or death over duration of trial),2,3 the pooled analysis resulted in a nominally significant reduction in risk of death across IPF and PPF for the 18mg nerandomilast dose vs placebo in monotherapy and with background nintedanib.1 The trend was more pronounced in monotherapy.1 “The new pooled data zoom in on nerandomilast’s potential as monotherapy, pairing efficacy with a nominally significant reduction in the risk of death. While the findings are exploratory, they add to the growing body of evidence and may impact future research directions in pulmonary fibrosis,” said Marlies Wijsenbeek, Erasmus MC University Medical Centre. “The new findings go hand-in-hand with nerandomilast’s favorable safety and tolerability profile in previous studies. In a disease area with many patients discontinuing treatment,4 mostly related to limited tolerability of current therapies, this could really improve outcomes for patients.” Findings of the pooled analysis In both FIBRONEER™ trials, patients (FIBRONEER™-IPF, n=1177; FIBRONEER™-ILD, n=1176) were randomized to receive nerandomilast 9mg twice per day, 18mg twice per day, or placebo.2,3 The data was pooled and changes in FVC over 76 weeks and clinically relevant outcomes (acute exacerbations, respiratory hospitalization, and death) were analyzed. The analyses included the overall population and subgroups of patients by use of background therapy at baseline.1 In the overall trial population, a nominally significant reduction in the risk of death by 43% was observed in patients who received 18mg (HR 0.57 [CI: 0.41-0.78)].1 A nominally significant reduction in the risk of death, by 59%, was observed in patients who received 18mg nerandomilast without background therapy (HR 0.41 [CI: 0.24-0.70)].1 This downward trend was also seen in patients taking background nintedanib with a nominally significant reduction in the risk of death by 41% (HR 0.59 [CI: 0.37-0.94)].1 “For people living with pulmonary fibrosis, mortality remains unacceptably high, with every second person dying within 5 years of diagnosis,” said Shashank Deshpande, Chairman of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “As the first Phase III trial program to demonstrate a nominally significant reduction in the risk of death in progressive pulmonary fibrosis, FIBRONEER heralds a significant advance for this group of patients, who face a devastating diagnosis and very limited treatment options.” In the pooled analysis, nerandomilast showed a favorable safety and tolerability profile, with a similar rate of discontinuation due to adverse events as placebo, consistent with the prior phase III results.1 The most frequent adverse event in the nerandomilast group without background therapy was diarrhea, reported in 14.6% in the placebo group, 17.5% in the nerandomilast 9 mg group, and 27.4% in the nerandomilast 18 mg group.1 Patients receiving either background nintedanib or pirfenidone reported diarrhea in 27.1% in the placebo group, in 41.9% in the 9mg nerandomilast group and in 47.7% in the 18mg nerandomilast group. In all patients, serious adverse events occurred in 44.7%, 39%, and 40.5% of patients treated with placebo, nerandomilast 9 mg, and nerandomilast 18 mg, respectively.1 These latest FIBRONEER™ findings reinforce nerandomilast’s potential as a new treatment for IPF and PPF.1 About nerandomilastNerandomilast (BI 1015550) is an investigational orally administered preferential inhibitor of phosphodiesterase 4B (PDE4B) that is being studied as a potential treatment for IPF and PPF.2,3 Its efficacy and safety has not been established. Nerandomilast was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of IPF in February 2022 and for the treatment of PPF in April 2025.7,8 The FDA recently granted priority review to the New Drug Application (NDA) for nerandomilast in IPF, with an anticipated action date in Q4 2025. An NDA for nerandomilast in PPF has also been filed. Regulatory submissions are under review in China, the UK, and the EU, with filings in other geographies to follow.8 About IPF and PPFIdiopathic pulmonary fibrosis (IPF) is one of the more common progressive fibrosing interstitial lung diseases (ILDs), primarily affecting people over 50 and more men than women.9 It is associated with breathlessness, persistent cough, fatigue, and reduced survival. With approximately half of patients dying within five years of diagnosis,5,6 IPF is deadlier than many forms of cancer.10,11 Patients with other types of fibrosing ILD can also develop a progressive phenotype, termed progressive pulmonary fibrosis (PPF). PPF is defined by worsening respiratory symptoms, physiological and radiological progression, despite management of the underlying cause.12 Globally, up to 3.6 million people may be affected by IPF and up to 5.6 million by PPF.12,13About Boehringer IngelheimBoehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. Our approximately 54,500 employees serve over 130 markets to build a healthier and more sustainable tomorrow. Learn more at http://www.boehringer-ingelheim.com/uk (UK) or www.boehringer-ingelheim.com (rest of world). References Oldham J, et al. (2025) Efficacy, safety and tolerability of nerandomilast in patients with pulmonary fibrosis: pooled data from the FIBRONEER-IPF and FIBRONEER-ILD trials. Poster, ERS 2025.Maher T et al. (2025) Nerandomilast in Patients with Progressive Pulmonary Fibrosis. N Engl J Med. 2025 Jun 12;392(22):2203-2214. DOI: 10.1056/NEJMoa2503643.Richeldi L, et al. Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med. 2025 Jun 12;392(22):2193-2202. DOI: 10.1056/NEJMoa2414108.Levra S et al. Long-term safety of antifibrotic drugs in IPF: a real-world experience. Biomedicines. 2022;10(12):3229. doi:10.3390/biomedicines10123229.Zheng Q et al. The global burden and temporal trends of interstitial lung disease: a systematic analysis from the Global Burden of Disease Study 2019. ERJ Open Res. 2022;8(1):00591-2021. DOI: 10.1183/23120541.00591‑2021.Cen Z et al. Outcomes and predictors of progression in progressive pulmonary fibrosis. Ann Med. 2024;56(1):2382949. DOI: 10.1080/07853890.2024.2406439.Boehringer Ingelheim (2022) FDA Grants BI 1015550 Breakthrough Therapy Designation for Idiopathic Pulmonary Fibrosis. Accessed September 2025. Available at: https://www.boehringer-ingelheim.com/us/human-health/lung-diseases/pulmonary-fibrosis/fda-grants-bi-1015550-breakthrough-therapy.Boehringer Ingelheim (2025) Global phase III trials demonstrate that nerandomilast slowed lung function decline in IPF and PPF, with similar discontinuation rates to placebo. Accessed September 2025. Available at: https://www.boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/phase-3-trials-nerandomilast-slowed-lung-function-decline-ipf-and-ppf. European Lung Foundation (2023) IPF - Idiopathic Pulmonary Fibrosis. Accessed April 2025. Available at: https://europeanlung.org/en/information-hub/factsheets/ipf-idiopathic-pulmonary-fibrosis/.Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA: A Cancer Journal for Clinicians. 2024;74(1):12–49. DOI: 10.3322/caac.21820.Vancheri C, Failla M, Crimi N, et al. Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology. Eur Respir J. 2010;35(3):496–504. DOI: 10.1183/09031936.00077309.Cottin V, Teague R, Nicholson L, Langham S, Baldwin M. The Burden of Progressive-Fibrosing Interstitial Lung Diseases. Front Med (Lausanne). 2022 Feb 1;9:799912. Doi: 10.3389/fmed.2022.799912. DOI: 10.3389/fmed.2022.799912.Podolanczuk AJ et al. Idiopathic pulmonary fibrosis: state of the art for 2023. Eur Respir J. 2023;61(4):2200957. DOI: 10.1183/13993003.00957‑2022.

United Therapeutics’ stock price soared Tuesday after the company reported a Phase 3 win in a lung disease that’s had a spate of failures. Tyvaso hit the primary goal in the TETON-2 trial in idiopathic pulmonary fibrosis (IPF). Patients who took Tyvaso for one year were able to more forcefully expel air from their lungs compared to those on placebo by a highly statistically significant margin. Tyvaso also achieved most of the study’s secondary endpoints. United’s shares $UTHR were up about 35% by midday Tuesday, hitting an all-time high at one point. There has been a recent string of clinical trial failures for IPF drugs from both large and small biopharma companies. Novartis ended a Phase 2 IPF study last October, and Pliant Therapeutics discontinued a Phase 2b study for its experimental IPF drug in March. Novartis did not disclose a reason for its discontinuation, while Pliant cited “an imbalance in unadjudicated IPF-related adverse events” between the two trial arms. Meanwhile, Boehringer Ingelheim last year touted multiple Phase 3 successes for its IPF drug nerandomilast. But that drug’s efficacy underwhelmed analysts once they saw the full data and began asking questions about the drug’s potential as a combination treatment and in the real world. Then in December, PureTech reported a successful Phase 2b readout showing that deupirfenidone appeared to stack up better against nerandomilast in cross-trial comparisons. Tyvaso’s latest results garnered no such pessimism. The magnitude of the United drug’s efficacy compared to other standard-of-care treatments is “unprecedented,” Leerink analyst Roanna Ruiz wrote in a note to investors. Tyvaso was also able to provide such a benefit for patients still taking other drugs, “positioning it uniquely in the IPF treatment landscape,” Ruiz added. The FDA usually requires two Phase 3 studies to succeed for this disease, and United is running another trial called TETON-1 that should read out in the first half of next year. While TETON-2 was a global study, TETON-1 enrolled patients in the US and Canada. Tuesday’s data significantly increase the likelihood that both studies end up being positive, according to TD Cowen analyst Joseph Thome. If TETON-1 ends up as another win and Tyvaso is approved, its peak global sales in IPF could reach $2.3 billion, Thome estimates. Tyvaso has been approved for another lung condition called pulmonary arterial hypertension since 2009. But in 2022, United got a separate formulation approved using an inhalation powder, compared to the original inhaled solution. The TETON-2 trial in IPF tested the original solution formulation.