Press Release: Global phase III trials demonstrate that nerandomilast slowed lung function decline in IPF and PPF, with similar discontinuation rates to placebo
-- Nerandomilast, an investigational agent, met the primary endpoint of both phase III trials, FIBRONEER-IPF and FIBRONEER-ILD, significantly reducing the decline in forced vital capacity (FVC) [mL] by absolute change from baseline at week 52, compared to placebo.1,2 -- Nerandomilast's safety and tolerability profile was consistent across both trials, with similar rates of permanent treatment discontinuation to placebo.1,2 -- In both trials the composite key secondary endpoint (time to first acute IPF/ILD exacerbation, first hospitalization for respiratory cause, or death) was not met. However, in the FIBRONEER-ILD trial, death occurred in a numerically smaller proportion of patients treated with nerandomilast than placebo.1,2 -- New drug applications for nerandomilast in idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) have been submitted in the US, China and the EU, with other geographies to follow.
Boehringer Ingelheim announced today detailed findings from the Phase III FIBRONEER-IPF and FIBRONEER-ILD trials. These studies evaluated nerandomilast, an investigational oral, preferential inhibitor of phosphodiesterase 4B (PDE4B), in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), respectively, with and without background antifibrotic therapy. Results were published in the New England Journal of Medicine and also presented as a late-breaking abstract at the American Thoracic Society (ATS) 2025 International Conference.
Nerandomilast is an investigational agent and has not been approved for use; its efficacy and safety has not been established.
Both trials met the primary endpoint at both doses, 9 mg and 18 mg, as measured by a reduction in the absolute change from baseline in forced vital capacity (FVC) [mL] decline at week 52 versus placebo.(1,2) FVC is a measure of lung function.(3)
"After several challenges in the scientific community to bring forward new clinical data, IPF and PPF continue to take a devastating toll on patients," said Toby Maher, M.D., Ph.D., Professor of Clinical Medicine, Keck School of Medicine, USC Los Angeles. "Having two phase III trials meet the primary endpoint is a major breakthrough for the scientific community, highlighting nerandomilast's potential to have a meaningful impact on patients' unmet needs, being studied as mono therapy or in combination with current treatments."
Across both trials, similar rates of permanent treatment discontinuation to placebo were observed: In FIBRONEER-IPF, adverse events led to permanent discontinuation of the trial regimen in 14.0% of the nerandomilast 18 mg group, 11.7% of the nerandomilast 9 mg group, and 10.7% of the placebo group.(1,2) In FIBRONEER-ILD, adverse events led to permanent discontinuation of the trial regimen in 10.0% of the nerandomilast 18 mg group, 8.1% in the nerandomilast 9 mg group, and 10.2% in the placebo group.(2) In both trials there were no imbalances between the nerandomilast and placebo groups with respect to adverse events of special interest such as vasculitis, depression, suicidality, or drug induced liver injury.(1,2)
"Idiopathic pulmonary fibrosis and progressive pulmonary fibrosis are devastating conditions, with one in two people dying within five years of IPF diagnosis. Despite this stark reality, ongoing research may provide new possibilities for patients, as there remains a need for additional therapies," said Shashank Deshpande, Head of Human Pharma and Member of the Board of Managing Directors at Boehringer Ingelheim. "The latest efficacy, safety and tolerability data on nerandomilast points to its potential in addressing the needs of those impacted by IPF and PPF."
FIBRONEER-IPF: Study Design and Results(1)
FIBRONEER-IPF ( https://www.boehringer-ingelheim.com/disclaimer/external?path=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05321069 NCT05321069) was a Phase III, double-blind, randomized, placebo-controlled trial evaluating the efficacy and safety of nerandomilast over at least 52 weeks in patients with IPF. A total of 1,177 patients across 36 countries were randomly assigned 1:1:1 to receive nerandomilast 9 mg twice-daily (n=392), nerandomilast 18 mg twice-daily (n=392), or placebo twice-daily (n=393). Randomization was stratified by use of background antifibrotic therapy, with 77.7% receiving nintedanib or pirfenidone at enrollment.
Key efficacy results at 52 weeks, as published in the New England Journal of Medicine, include:
Placebo Nerandomilast 9 mg Nerandomilast 18 mg
twice-daily twice-daily
Primary Endpoint (adjusted mean change from baseline
in FVC)
All patients -183.5 mL (n=391) -138.6 mL (n=390) -114.7 mL (n=392)
(95% confidence interval [CI]: (95% CI: -165.6 to -111.6) (95% CI: -141.8 to - 87.5)
-210.9 to -156.1)
Subgroups of Primary Endpoint (adjusted mean change
from baseline in FVC)*
*Trial was not powered to show a difference for these
subgroups
No -148.7 mL (n=87) -70.4 mL (n=86) -79.2 mL (n=87)
background
antifibrotic
therapy
Background -191.6 mL (n=172) -130.7 mL (n=184) -118.5 mL (n=178)
nintedanib
Background -197.0 mL (n=132) -201.8 mL (n=120) -133.7 mL (n=127)
pirfenidone
The composite key secondary endpoint (time to first acute IPF exacerbation, first hospitalization for respiratory cause, or death) was not met.
The most frequent adverse event was diarrhea, reported in 16.0% of the placebo group, 31.1% of the nerandomilast 9 mg group, and 41.3% of the nerandomilast 18 mg group. The adverse event that most frequently led to discontinuation of the trial regimen was diarrhea, with 1.8% in the nerandomilast 9 mg group, 6.1%, in the nerandomilast 18 mg group, and in 0.5% in the placebo group discontinuing treatment. Other adverse events were balanced across treatment groups, specifically showing no imbalances between the nerandomilast and placebo groups in adverse events of special interest such as vasculitis, depression, suicidality, or drug-induced liver injury. Adverse events led to treatment discontinuation more frequently among patients taking background antifibrotic therapy across treatment groups. Serious adverse events occurred in 33%, 31%, and 30% of patients treated with placebo, nerandomilast 9 mg, and nerandomilast 18 mg, respectively. Adverse events were fatal in 5%, 4%, and 2% of patients treated with placebo, nerandomilast 9 mg, and nerandomilast 18 mg, respectively.
FIBRONEER-ILD: Study Design and Results(2)
FIBRONEER-ILD ( https://www.boehringer-ingelheim.com/disclaimer/external?path=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05321082%3Ftab%3Dresults NCT05321082) was a Phase III, double-blind, randomized, placebo-controlled trial evaluating the efficacy and safety of nerandomilast over at least 52 weeks in patients with PPF. A total of 1,176 patients across 44 countries were randomly assigned 1:1:1 to receive nerandomilast 9 mg twice-daily (n=393), nerandomilast 18 mg twice-daily (n=391), or placebo twice-daily (n=392). Randomization was stratified by use of background antifibrotic therapy, with 43.5% receiving nintedanib.
Key efficacy results at 52 weeks, as published in the New England Journal of Medicine, include:
Placebo Nerandomilast 9 mg Nerandomilast 18 mg
twice-daily twice-daily
Primary Endpoint (adjusted mean change from baseline
in FVC)
All -165.8 mL (n=391) -84.6 mL (n=390) -98.6 mL (n=390)
patients (95% CI: -190.5 to -141.0) (95% CI: -109.6 to -59.7) (95% CI: -123.7 to -73.4)
Subgroups of Primary Endpoint (adjusted mean change
from baseline in FVC)*
*Trial was not powered to show a difference for these
subgroups
No -154.1 mL (n=222) -82.3 mL (n=217) -95.2 mL (n=220)
background (95% CI: -187.1 to -121.2) (95% CI: -115.9 to -48.8) (95% CI: -128.6 to -61.9)
Background -180.9 mL (n=169) -87.8 mL (n=173) -102.9 mL (n=170)
nintedanib (95% CI: -218.6 to -143.2) (95% CI: -125.4 to -50.2) (95% CI: -141.2 to -64.5)
2 patients in this group took pirfenidone rather than nintedanib. These were classified as protocol deviations, but the data from these patients were analyzed as part of the background nintedanib group.
Nerandomilast was not statistically significant for the composite key secondary endpoint (time to first acute exacerbation, hospitalization for a respiratory cause, or death), but there were numerically fewer deaths in both treatment groups: 9 mg group (n=33/8.4%), 18 mg group (n=24/6.1%), versus placebo (n=50/12.8%).
The safety and tolerability profile of nerandomilast was largely consistent with FIBRONEER-IPF. The most frequent adverse event was diarrhea, reported in 24.7% of the placebo group, 29.5% of the nerandomilast 9 mg twice daily group, and 36.6% of the nerandomilast 18 mg twice daily group over 52 weeks. There were no imbalances between the nerandomilast and placebo groups in adverse events of special interest such as vasculitis, depression, or suicidality. The adverse events that most frequently led to treatment discontinuation were 'condition aggravated' (i.e., worsening of pulmonary fibrosis) which led to discontinuation in 1.5% in the nerandomilast 9 mg group, 1.0%, in the nerandomilast 18 mg group, and in 3.1% in the placebo group, and diarrhea, which led to discontinuation in 1.3%, 2.6%, and 0.5% of these treatment groups, respectively. The incidence of adverse events that led to treatment discontinuation was generally similar among patients taking background nintedanib therapy and patients not taking background nintedanib therapy. Serious
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Press Release: Global phase III trials -2-
adverse events occurred in 35.2%, 31.8%, and 33.2% of patients treated with placebo, nerandomilast 9 mg, and nerandomilast 18 mg, respectively. Adverse events were fatal in 5.1%, 3.6%, and 2.0% of patients treated with placebo, nerandomilast 9 mg, and nerandomilast 18 mg, respectively.
About nerandomilast
Nerandomilast (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.(1,2)
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. The U.S. FDA recently granted priority review to the New Drug Application (NDA) for nerandomilast in IPF, with an anticipated action date in the fourth quarter of 2025. An NDA for nerandomilast in PPF has also been filed with the FDA. Regulatory submissions for nerandomilast in IPF and PPF are also under review in China and the EU, with filings in other geographies to follow.
About IPF and PPF
IPF is one of the more common progressive fibrosing interstitial lung diseases (ILDs).(4) In IPF, the root cause of pulmonary fibrosis is not known. Symptoms of IPF include breathlessness during activity, a dry and persistent cough, fatigue and weakness.(5) The disease primarily affects patients over the age of 50 and affects more men than women.(5)
Patients with certain types of non-IPF fibrosing ILD may also develop a progressive phenotype known as PPF. In PPF, there is often a known underlying disease (e.g. rheumatoid arthritis or systemic sclerosis) cause for the ILD.(6) In ILDs other than IPF, PPF is defined by worsening respiratory symptoms, physiological evidence of disease progression and radiological evidence of disease progression.(6)
The prevalence of IPF and PPF varies by region. It is estimated that up to 3.6 million people could be affected by IPF worldwide and up to 5.6 million by PPF.(7,8)
About Boehringer Ingelheim
Boehringer 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 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. More than 54,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Learn more at https://www.boehringer-ingelheim.com/disclaimer/external?path=http%3A%2F%2Fwww.boehringer-ingelheim.com%2Fuk http://www.boehringer-ingelheim.com/uk (UK) or https://www.boehringer-ingelheim.com/disclaimer/external?path=http%3A%2F%2Fwww.boehringer-ingelheim.com www.boehringer-ingelheim.com (rest of world).
References
(1) Richeldi L, et al. (2025) Nerandomilast in patients with idiopathic pulmonary fibrosis. In: NEJM. 2025.
(2) Maher TM, et al. (2025) Nerandomilast in patients with progressive pulmonary fibrosis. In: NEJM. 2025.
(3) Twisk JWR et al. (1998). Tracking of lung function parameters and the longitudinal relationship with lifestyle. European Respiratory Journal. 12(3):627--634.
(4) Sauleda J, et al. Idiopathic Pulmonary Fibrosis: Epidemiology, Natural History, Phenotypes. Med Sci (Basel). 2018 Nov 29;6(4):110. doi: 10.3390/medsci6040110. PMID: 30501130; PMCID: PMC6313500.
(5) European Lung Foundation (2023) IPF - Idiopathic Pulmonary Fibrosis. Accessed April 2025. Available at: https://www.boehringer-ingelheim.com/disclaimer/external?path=https%3A%2F%2Feuropeanlung.org%2Fen%2Finformation-hub%2Ffactsheets%2Fipf-idiopathic-pulmonary-fibrosis%2F https://europeanlung.org/en/information-hub/factsheets/ipf-idiopathic-pulmonary-fibrosis/.
(6) Podolanczuk AJ, Fernández Peréz ER. Identification, course, and management of progressive pulmonary fibrosis. Am J Manag Care. 2024 Oct;30(7 Suppl):S122-S130. doi: 10.37765/ajmc.2024.89634. PMID: 39495032.
(7) Maher TM, Bendstrup E, Dron L, Langley J, Smith G, Khalid JM, Patel H, Kreuter M. Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir Res. 2021 Jul 7;22(1):197. doi: 10.1186/s12931-021-01791-z. PMID: 34233665; PMCID: PMC8261998.
(8) 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. PMID: 35178411; PMCID: PMC8843847. Assuming a world population of 8bn
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