Nerandomilast

Boehringer Ingelheim (BI) has announced positive top-line results from a late-stage study of its investigational nerandomilast in progressive pulmonary fibrosis (PPF). The phase 3 FIBRONEER-ILD trial randomised more than 1,170 PPF patients to receive one of two doses of the oral candidate or placebo twice daily for at least one year. The study met its primary endpoint by demonstrating an absolute change from baseline in forced vital capacity (FVC), a measure of lung function, at week 52 versus placebo. The results come five months after BI revealed that its phase 3 FIBRONEER-IPF of nerandomilast in idiopathic pulmonary fibrosis (IPF) met the same FVC primary endpoint. BI said in the September announcement that it would be submitting a new drug application (NDA) for nerandomilast in IPF to the US Food and Drug Administration (FDA) and other health authorities worldwide. Based on the new results from FIBRONEER-ILD, the company will now also be submitting an NDA for the drug in PPF. IPF is one of the more common progressive fibrosing interstitial lung diseases (ILD), affecting approximately three million people worldwide. The condition, which primarily affects those aged over 50 years, causes the lungs to become scarred and results in symptoms such as breathlessness during activity, a dry and persistent cough, fatigue and weakness. Patients with certain types of non-IPF fibrosing ILD may also develop PPF, characterised by worsening respiratory symptoms, as well as physiological and radiological evidence of disease progression. Nerandomilast is a preferential inhibitor of phosphodiesterase 4B, which is highly expressed in the lungs, where it may play a key role in fibrosis and inflammation. Shashank Deshpande, head of human pharma and a member of the board of managing directors at BI, said: “The positive FIBRONEER-ILD top-line result shows the potential of nerandomilast in PPF. The hope is that the safety and tolerability profile we are initially seeing could potentially help to reduce treatment challenges.” The results come after BI entered into a strategic partnership with Brainomix in July to improve the identification and access to treatment for people living with fibrosing lung disease in the US.

INGELHEIM, Germany I February 10, 2025 I 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™-IPF 4 in people living with IPF and FIBRONEER™-ILD 5 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: 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: 1 Boehringer 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 2 Maher 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. 3 Richeldi L, et al. (2022) Trial of a Preferential Phosphodiesterase 4B Inhibitor for Idiopathic Pulmonary Fibrosis. In: N Engl J Med 2022;386:2178-2187. 4 Boehringer 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 5 Boehringer 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 6 Boehringer 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 7 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. 8 European Lung Foundation (2023) IPF – Idiopathic Pulmonary Fibrosis. Accessed January 2025. Available at: https://europeanlung.org/en/information-hub/factsheets/ipf-idiopathic-pulmonary-fibrosis/ 9 Koudstaal T, et al. (2023) Idiopathic pulmonary fibrosis. In: Presse Med 2023; 52(3):104166 10 Cottin, 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 11 Brown 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. SOURCE: Boehringer Ingelheim