Boehringer's nerandomilast meets primary endpoint in pivotal phase-III FIBRONEER™-IPF study 发布时间：2024-09-16 来源：Boehringer Ingelheim

• Topline data from FIBRONEER™-IPF 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™-IPF trial is the largest trial in idiopathic pulmonary fibrosis (IPF) conducted to date. Patients were recruited in over 330 sites and in over 30 countries.1,5
• Full efficacy and safety data from the trial will be presented in the first half of 2025.
• Boehringer Ingelheim will submit a new drug application for nerandomilast for the treatment of IPF to the US FDA and other Health Authorities worldwide.

Boehringer Ingelheim announced today that the FIBRONEER™-IPF trial met its primary endpoint, which was the absolute change from baseline in Forced Vital Capacity [mL] (FVC) at week 52 versus placebo. FVC is a measure of lung function.1

Based on these results, Boehringer Ingelheim will submit the new drug application for nerandomilast for the treatment of IPF to the US Food & Drug Administration (FDA) and other Health Authorities worldwide. The FDA granted Breakthrough Therapy Designation in IPF in 2022.2

“This is the first IPF phase-III-trial in a decade to meet its primary endpoint9,” said Ioannis Sapountzis, Head of Global Therapeutic Areas at Boehringer Ingelheim. “Today’s announcement represents the next step in our long history in the research of this disease. IPF has a high unmet need for patients, and we are continuously fostering our research activities to develop more options for one of the most common interstitial lung diseases.”

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

About FIBRONEER™-IPF (NCT05321069)4

A Double Blind, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of nerandomilast Over at Least 52 Weeks in Patients With Idiopathic Pulmonary Fibrosis (IPF).

Primary endpoint: Absolute change from baseline in Forced Vital Capacity (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 IPF exacerbation; first hospitalization for respiratory cause; or death (whichever occurs first) over the duration of the trial.

Participants are put into 3 groups randomly, which means by chance. Participants in 2 groups take different doses of nerandomilast as tablets twice a day. Participants in the placebo group take placebo tablets twice a day. Placebo tablets look like nerandomilast tablets but do not contain any medicine.

The trial has been conducted in more than 30 countries,1 and randomized 1177 patients. 

About the FIBRONEER™ clinical program4,5

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

Patients participating in the FIBRONEER™-IPF trial were treated with either oral nerandomilast at twice-daily doses of 9 mg or 18 mg, or placebo, over at least 52 weeks.1 The 18 mg twice-daily dose of nerandomilast is supported by the results from the Phase II study.1 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.1

In both trials, the primary endpoint is the absolute change from baseline in FVC at week 52. 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/PPF exacerbation, first hospitalization for respiratory cause, or death (whichever occurs first) over the duration of the trials.4,5

About nerandomilast

Nerandomilast (BI 1015550) is an investigational oral, preferential inhibitor of phosphodiesterase 4B (PDE4B) that is being studied as a potential treatment for idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).2 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 idiopathic pulmonary fibrosis (IPF) in February 2022.2 

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). 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). Symptoms of IPF include breathlessness during activity, a dry and persistent cough, chest discomfort, fatigue and weakness. Although considered “rare,” IPF affects approximately 3 million people worldwide.6,7 The disease primarily affects patients over the age of 50 and affects more men than women.6 

In addition to IPF, patients with certain types of fibrosing ILD may develop a progressive phenotype known as progressive pulmonary fibrosis (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.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 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 https://www.boehringer-ingelheim.com/uk (UK) or https://www.boehringer-ingelheim.com (rest of world).

References:

1Richeldi L, et al. (2023) Design of a phase III, double-blind, randomised, placebo-controlled trial of BI 1015550 in patients with idiopathic pulmonary fibrosis (FIBRONEER-IPF). In: BMJ Open Respir Res. 2023; 10(1): e001563.

2Boehringer Ingelheim (2022) FDA Grants BI 1015550 Breakthrough Therapy Designation for Idiopathic Pulmonary Fibrosis. Accessed August 2024. Available at: https://www.boehringer-ingelheim.com/us/human-health/lung-diseases/pulmonary-fibrosis/fda-grants-bi-1015550-breakthrough-therapy.

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 August 2024. 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 August 2024. Available at: https://clinicaltrials.gov/study/NCT05321082?tab=results.

6European Lung Foundation (2023) IPF - Idiopathic Pulmonary Fibrosis. Accessed August 2024. Available at: https://europeanlung.org/en/information-hub/factsheets/ipf-idiopathic-pulmonary-fibrosis/

7Koudstaal T, Wijsenbeek MS. Idiopathic pulmonary fibrosis. Presse Med 2023; 52(3):104166.

8Cottin, V. Am J Respir Crit Care Med 2023; 207(1):11-13. 

9King TE Jr et al (2014) A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. In: N Engl J Med 2014:370:2083-2092.