Boehringer’s nerandomilast meets primary endpoint in Phase III study FIBRONEER™-ILD, in progressive pulmonary fibrosis

• Topline data from FIBRONEER™-ILD show that the investigational compound nerandomilast met its primary endpoint, which was the absolute change from baseline in forced vital capacity [mL] at week 52 versus placebo
• The FIBRONEER™-ILD trial is the second Phase III trial in which the investigational compound nerandomilast has met its primary endpoint¹
• Initial safety and tolerability results of the FIBRONEER™-trials are generally consistent with the Phase II results in IPF; full efficacy and safety data from FIBRONEER™-ILD will be shared in the second quarter of 2025
• Boehringer Ingelheim will submit a new drug application for nerandomilast for the treatment of PPF to the US Food & Drug Administration (FDA) and other health authorities worldwide

Boehringer Ingelheim announced today that the FIBRONEER™-ILD trial met its primary endpoint, which was the absolute change from baseline in forced vital capacity (FVC) [mL] at week 52 versus placebo. FVC is a measure of lung function.² Initial data readouts of the FIBRONEER™-trials support a generally consistent safety and tolerability profile when compared to the Phase II idiopathic pulmonary fibrosis (IPF) study, with overall adverse events comparable to those seen in the placebo group.³

Nerandomilast is an investigational oral, preferential inhibitor of phosphodiesterase 4B (PDE4B).³ As it has not been approved for use, safety and efficacy have not been established. It is being investigated as part of the FIBRONEER™ global program, which includes two Phase III studies —FIBRONEER™-IPF⁴ in people living with IPF and FIBRONEER™-ILD⁵ in people living with progressive pulmonary fibrosis (PPF). 

Based on these results, Boehringer Ingelheim will submit a new drug application for nerandomilast for the treatment of PPF to the US FDA and other health authorities worldwide.

“The positive FIBRONEER™-ILD topline result shows the potential of nerandomilast in progressive pulmonary fibrosis. The hope is that the safety and tolerability profile we are initially seeing could potentially help to reduce treatment challenges,” said Shashank Deshpande, Head of Human Pharma and Member of the Board of Managing Directors at Boehringer Ingelheim. “The recent milestones of the FIBRONEER™ trial program underscore our commitment to transforming the lives of patients with this debilitating disease, and are a testament to Boehringer Ingelheim's position at the forefront of pulmonary fibrosis research.”

About FIBRONEER™-ILD (NCT05321082)⁵

FIBRONEER™-ILD was a double-blind, randomized, placebo-controlled trial evaluating the efficacy and safety of nerandomilast (BI 1015550) over at least 52 weeks in patients with PPF.

Primary endpoint: Absolute change from baseline in FVC (mL) at week 52. 

Key secondary endpoint: 

• Time to the first occurrence of any of the components of the composite endpoint: time to first acute interstitial lung disease (ILD) exacerbation; first hospitalization for respiratory cause; or death (whichever occurs first) over the duration of the trial.

Patients participating in the FIBRONEER™-ILD trial were treated with either oral nerandomilast 9 mg or 18 mg, or placebo, twice-daily, over at least 52 weeks. The 18 mg twice-daily dose of nerandomilast is supported by the results from the Phase II study.² An additional 9 mg twice-daily dose of nerandomilast was added to evaluate the benefit-risk profile at a lower dose, as well as to provide further dose-response and exposure-response data.²

The trial has been conducted in more than 40 countries, more than 400 locations, and enrolled 1178 patients.

About the FIBRONEER™ clinical program

The FIBRONEER™ program includes two Phase III randomized, double-blind, placebo-controlled trials — FIBRONEER™-IPF (NCT05321069)⁴ and FIBRONEER™-ILD (NCT05321082)⁵ — to investigate the efficacy, safety and tolerability of nerandomilast over at least 52 weeks in patients with IPF and in patients with PPF. 

In both trials, the primary endpoint is the absolute change from baseline in FVC (mL) at week 52.^4,5 The key secondary endpoint is the time to the first occurrence of any of the components of the composite endpoint: time to first acute IPF/ILD exacerbation, first hospitalization for respiratory cause, or death (whichever occurs first) over the duration of the trials.

About nerandomilast

Nerandomilast (BI 1015550) is an investigational oral, preferential inhibitor of phosphodiesterase 4B (PDE4B) that is being studied as a potential treatment for IPF and PPF.3,4,5 This compound is an investigational agent and has not been approved for use. The efficacy and safety of this investigational compound has not been established.

Nerandomilast was granted FDA Breakthrough Therapy Designation for the treatment of IPF in February 2022.⁶

The efficacy, safety, and tolerability of nerandomilast was studied in a Phase II randomized, double-blind, placebo-controlled trial of patients with IPF (n=147).³ The primary endpoint was a change from baseline in FVC (a measure of lung function) over a 12-week treatment period.³

About IPF and PPF

IPF is one of the more common progressive fibrosing interstitial lung diseases (ILD).⁷ Symptoms of IPF include breathlessness during activity, a dry and persistent cough, fatigue and weakness.⁸ Although considered “rare,” IPF affects approximately 3 million people worldwide.^8,9 The disease primarily affects patients over the age of 50 and affects more men than women.⁸

Patients with certain types of non-IPF fibrosing ILD may also develop a progressive phenotype known as PPF. In ILDs other than IPF, progressive pulmonary fibrosis is defined by worsening respiratory symptoms, physiological evidence of disease progression and radiological evidence of disease progression.¹⁰

Progressive pulmonary fibrosis can cause irreversible lung damage and lead to early mortality.^10,11

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 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. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Learn more at www.boehringer-ingelheim.com/uk (UK) or www.boehringer-ingelheim.com (rest of world).

References:

¹Boehringer Ingelheim (2024) Boehringer’s nerandomilast meets primary endpoint in pivotal phase-III FIBRONEER™-IPF study. Accessed January 2025. Available at: https://www.boehringer-ingelheim.com/us/topline-results-boehringers-phase-iii-ipf-study

²Maher TM, et al. (2023) Design of a phase III, double-blind, randomised, placebo-controlled trial of BI 1015550 in patients with progressive pulmonary fibrosis (FIBRONEER-ILD). In: BMJ Open Respir Res 2023;10:e001580.

³Richeldi L, et al. (2022) Trial of a Preferential Phosphodiesterase 4B Inhibitor for Idiopathic Pulmonary Fibrosis. In: N Engl J Med 2022;386:2178-2187.

⁴Boehringer Ingelheim (2024) A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Idiopathic Pulmonary Fibrosis (IPF). Accessed January 2025. Available at: https://clinicaltrials.gov/study/NCT05321069

⁵Boehringer Ingelheim (2024) A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs). Accessed January 2025. Available at: https://clinicaltrials.gov/study/NCT05321082?tab=results

⁶Boehringer Ingelheim (2022) FDA Grants BI 1015550 Breakthrough Therapy Designation for Idiopathic Pulmonary Fibrosis. Accessed January 2025. Available at: https://www.boehringer-ingelheim.com/us/human-health/lung-diseases/pulmonary-fibrosis/fda-grants-bi-1015550-breakthrough-therapy

⁷Sauleda 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.

⁸European Lung Foundation (2023) IPF - Idiopathic Pulmonary Fibrosis. Accessed January 2025. Available at: https://europeanlung.org/en/information-hub/factsheets/ipf-idiopathic-pulmonary-fibrosis/

⁹Koudstaal T, et al. (2023) Idiopathic pulmonary fibrosis. In: Presse Med 2023; 52(3):104166

¹⁰Cottin, V. et al. (2023) Criteria for Progressive Pulmonary Fibrosis: Getting the Horse Ready for the Cart. In: Am J Respir Crit Care Med 2023; 207(1):11-13

¹¹Brown KK, Martinez FJ, Walsh SLF, Thannickal VJ, Prasse A, Schlenker-Herceg R, et al. The natural history of progressive fibrosing interstitial lung diseases. Eur Respir J 2020;55:2000085.

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