To improve the lives of patients with pulmonary fibrosis

Pulmonary fibrosis is a devastating condition that makes even simple tasks an exhausting challenge; and it is still without a cure. Boehringer Ingelheim is committed to bringing new, urgently needed therapies to people living with this disease. Clinical trials spanning over 40 countries have shown the potential of our investigational therapy, nerandomilast, to surpass the current standard of care for pulmonary fibrosis.

The chemical compound nerandomilast never ceases to surprise Dr. Peter Nickolaus, pharmacology program lead in immunology and respiratory diseases research at Boehringer Ingelheim. Over a quarter of a century, he has witnessed up close how it evolved into an investigational drug that could change the treatment landscape for pulmonary fibrosis. “It means a lot to me that I have been able to follow and accompany the development from the beginning,” says Nickolaus.

This compound’s journey illustrates the unique challenges and unexpected health opportunities that arise in the drug development process as a long-term team effort – ultimately leading to medications that can positively impact the lives of patients.

It means a lot to me that I have been able to follow and accompany the program development from the beginning. Dr. Peter Nickolaus, pharmacology program lead in immunology and respiratory diseases research at Boehringer Ingelheim

New treatments needed for pulmonary fibrosis

Nerandomilast’s story begins in 2000, when the compound BI 1015550 was first developed as a potential treatment for chronic obstructive pulmonary disease (COPD). In 2012 it was decided it could be more effective as a treatment for pulmonary fibrosis.

Pulmonary fibrosis is a devastating condition with no cure. Characterized by a buildup of scar tissue in the lungs, making it more and more difficult for oxygen to enter the blood, it leads to shortness of breath, a dry cough, fatigue, and a diminished ability to do everyday activities. The disease’s impact on a patient’s health and quality of life can be severe, with even simple tasks becoming exhausting challenges due to impaired lung function. Despite advances in therapy over the past decade, new treatments are urgently needed to help slow, if not stop the disease progression.

What happens in the lung when you have pulmonary fibrosis

There are more than 200 lung disorders that can lead to pulmonary fibrosis. Idiopathic pulmonary fibrosis, which means that the exact underlying disease is unknown, affects about three million people worldwide and is one of the most progressive forms of the condition. “It’s a devastating disease, that’s still hard to treat,” says Dr. Susanne Stowasser, associate head of medicine in therapeutic area inflammation at Boehringer, who also encountered many patients living with the condition during her time as a clinical pulmonologist.

Life expectancy after diagnosis can be as little as three years if left untreated, and there is no cure for the condition. Getting a diagnosis itself can prove to be a difficult task. Early symptoms of pulmonary fibrosis bear resemblance to a variety of other conditions, meaning primary care physicians often do not recognize the disease at first. And for the longest time, treatments for pulmonary fibrosis were practically non-existent.

Patients have become our partners in clinical research. There has been a clear shift from development for patients to development with patients. Dr. Susanne Stowasser, associate head of medicine in therapeutic area inflammation at Boehringer

Unmet medical needs still remain

In 2014, nintedanib (OFEV®), developed by Boehringer, was one of only two treatments approved for idiopathic pulmonary fibrosis (IPF). Clinical trials found it was able to slow down the progression of the lung disease. However, due to the nature of the drug’s mechanism of action, it also produced gastrointestinal side effects, such as nausea, vomiting, and diarrhea.

“Real-world data indicate that both approved treatment options in IPF are associated with side effects, and this can be one of the reasons that patients cannot stay on the full dose of the drug or even have to stop using the drug,” Stowasser says.

More than 100 years of leadership in lung health

Boehringer Ingelheim has 100 years of heritage in respiratory diseases. Since 1921 we have emerged as a leader in this disease area, having launched several treatments in a range of respiratory conditions, including asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF). Our focus is on improving the quality of life of patients suffering from debilitating respiratory diseases and enabling them to maintain a more independent life.

1921

Launch of the first respiratory drug Lobelin®

1941

Boehringer’s first asthma treatment ALUDRIN® is launched

1972

BEROTEC® is Boehringer’s first asthma drug to be administered by inhaler

1975

Launch of ATROVENT® for the treatment of chronic respiratory diseases

1980

BERODUAL® for the treatment of chronic obstructive pulmonary disease (COPD) is launched

2002

Market launch of SPIRIVA® for the treatment of patients with COPD

2007

SPIRIVA® RESPIMAT® – an innovative inhaler – becomes available

2013

GIOTRIF® is launched – the first oncology product of Boehringer for the treatment of patients with non-small cell lung cancer (NSCLC)

2015

Launch of OFEV® for the treatment of idiopathic pulmonary fibrosis (IPF), and VARGATEF®, another treatment for NSCLC patients. Both drugs have the same active pharmaceutical ingredient: nintedanib. SPIRIVA® RESPIMAT® is approved for bronchial asthma

2015

SPIOLTO® RESPIMAT® is launched for COPD

2019/2020

Further market authorizations for OFEV® for the treatment of systemic sclerosis with interstitial lung disease (SSc-ILD) and other chronic ILDs with a progressive phenotype beyond IPF

Hope for patients with pulmonary fibrosis

“Nerandomilast started out as a potential treatment for COPD,” says Nickolaus. “Then we tested it as a potential treatment for pulmonary fibrosis – and here it worked nicely!” he recalls.

In a Phase II study, nerandomilast showed a similar occurrence of serious or severe side effects than the placebo group. The development team concluded that, if confirmed in a Phase III study, this would constitute a significant improvement in pulmonary fibrosis care. “A better adverse event profile may be due to the fact that it is an innovative investigational phosphodiesterase (PDE) 4B inhibitor. Meaning it targets preferentially the PDE4B member of the PDE4 family of proteins, rather than the PDE4D member, which is where the side effects, such as vomiting, nausea, and diarrhea, are thought to originate,” says Nickolaus.

More than 200 lung disorders can lead to pulmonary fibrosis

Around 3 million people worldwide are affected by IPF

As little as 3 years of life expectancy after diagnosis if left untreated

Positive results in first clinical trials

Nerandomilast is currently in Phase III clinical trials in a global clinical trial program called FIBRONEER™ that is being conducted in more than 40 countries. The FIBRONEER™-IPF and the FIBRONEER™-ILD trials include more than 1,170 patients with idiopathic pulmonary fibrosis and progressive pulmonary fibrosis, respectively, and have reached their primary endpoints. “We expect to present the results from both FIBRONEER™-IPF and FIBRONEER™-ILD trials in the first half of 2025. This is great news for patients as these are the first Phase III trials in the last decade that came through with positive results for these difficult to treat conditions,” says Stowasser.

The FIBRONEER™-IPF and FIBRONEER™-ILD trials are the first Phase III trials in the last decade that came through with positive results for these difficult to treat conditions.

Before reaching the primary endpoint in the first positive trials in pulmonary fibrosis for more than a decade, the drug was already granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration in 2022 for the treatment of idiopathic pulmonary fibrosis, and Orphan Drug Designation for idiopathic pulmonary fibrosis in the same year.

The work isn’t finished yet, though. The ultimate goal is finding a drug that stops, rather than slows, the progression of pulmonary fibrosis. For researchers such as Nickolaus and Stowasser, nerandomilast is more than just a project that’s finally coming to fruition. It’s a testament to perseverance and the collective vision of everyone involved in its development and in bringing life-changing therapies to pulmonary fibrosis patients.

Boehringer Ingelheim’s commitment:

Boehringer is leading the field in finding ways to restore lung health and improve the daily lives of those suffering from pulmonary fibrosis. Its vision is to target scientific breakthroughs that seek to restore lung health and ultimately prevent pulmonary fibrosis. Part of this work has been informed by long-term committed collaborations with the patient community, which has included onboarding patients as advisors – such as in study simulations – and taking their recommendations into account. “Patients have become our partners in clinical research,” says Susanne Stowasser. “There has been a clear shift from development for patients to development with patients in the last couple of years.