Boehringer Ingelheim Completes Enrollment of Pivotal Phase III Studies for Nintedanib (BIBF 1120) in Idiopathic Pulmonary Fibrosis

IPF is a progressive and severely debilitating lung disease with a high mortality rate; there are no approved treatments in the United States

Sep 26, 2012, 09:00 ET from Boehringer Ingelheim Pharmaceuticals, Inc.

RIDGEFIELD, Conn., Sept. 26, 2012 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. announced that clinical trial enrollment has completed for two phase III studies evaluating the safety and efficacy of nintedanib (BIBF 1120), an investigational compound, in patients with idiopathic pulmonary fibrosis (IPF), being studied at a twice-daily oral dose. There are no approved treatments in the U.S. for IPF, a progressive and severely debilitating lung disease with a high mortality rate: approximately 60 percent of patients with IPF die from the disease within two to five years of diagnosis. IPF is characterized by inflammation and scarring of lung tissue, called fibrosis, and over time, the lungs lose their ability to take in and transfer oxygen into the bloodstream, and vital organs do not get enough oxygen. As a result, individuals with IPF experience shortness of breath and often have difficulty participating in everyday physical activities. Research indicates that IPF may affect approximately 100,000 Americans.

In June 2011, the U.S. Food and Drug Administration (FDA) granted nintedanib orphan drug status, which identifies compounds for rare diseases.

"With no FDA-approved treatments, today's standard of IPF care is limited to oxygen therapy and lung transplant for some patients," said Dr. Kevin R. Flaherty, a study investigator and associate professor in the Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System. Dr. Flaherty is a paid member of Boehringer Ingelheim's nintedanib clinical trial steering committee. "IPF patients desperately need safe and effective treatments to not only reduce the decline in lung function and eventually decrease mortality, but also to stabilize health-related quality of life and delay or reduce sudden worsening of symptoms, or acute exacerbations. These are hallmarks of IPF and are often times unpredictable and can cause death."

The two global phase III studies are identical in design, constructed as double-blind, randomized, placebo-controlled trials with a 52-week duration and matching twice-daily 150 mg dosing, inclusion criteria and endpoints. The primary endpoint is the annual rate of decline in forced vital capacity (FVC), or the volume of air that is expelled into a spirometer following maximum inhalation. Reductions in FVC are reflected in impaired ventilation capacity of the lungs. Measuring FVC is a part of the examinations conducted in IPF patients and is scientifically accepted for assessment of IPF treatment effects. Secondary endpoints include health-related quality of life, exacerbations, respiratory mortality, overall survival and on-treatment survival. The trials have enrolled a total of 970 patients in 20 countries. The first patients entered the trials in April and May 2011, respectively.

"There is a clear need for approved treatments for IPF patients and we look forward to completing the trials and analyzing results from the phase III studies," said Tunde Otulana, MD, vice president, Clinical Development and Medical Affairs, Respiratory at Boehringer Ingelheim Pharmaceuticals, Inc. "Boehringer Ingelheim is committed to ongoing research which we hope will help identify a safe and effective therapeutic option." 

About Nintedanib

Nintedanib is an investigational small molecule tyrosine kinase inhibitor (TKI) in development by Boehringer Ingelheim for IPF. It targets three growth factors: the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR). These receptors have been shown to be potentially involved in pathomechanisms of pulmonary fibrosis. By blocking these signaling pathways that are involved in fibrotic processes, it is hypothesized that there may be potential to reduce disease progression, and thereby slow the decline of lung function. Nintedanib is also in clinical development and under evaluation as a possible treatment option for cancer, including non-small cell lung cancer, ovarian cancer, colorectal cancer and hepatocellular carcinoma.

About the Phase III Trials

The two phase III clinical trials are 52-week, double-blind, randomized, placebo-controlled trials evaluating the effect of oral nintedanib, 150 mg twice daily, on annual FVC decline, in IPF.

The primary endpoint is annual rate of decline in FVC (expressed in mL over 52 weeks). The secondary endpoints are; change from baseline in Saint-George Respiratory Questionnaire (SGRQ); time to first acute exacerbation (days); respiratory mortality; overall survival; on-treatment survival; further analysis of FVC; further analysis of acute exacerbations; patient reported outcomes: changes in SGRQ, Shortness Of Breath Questionnaire (SOBQ), Cough And Sputum Assessment (CASAQ), Patient's Global Impression of Change (PGIC), EuroQol 5-Dimensional Quality of Life Questionnaire (EQ5D); time to death or lung transplant.

Eligibility inclusion criteria was based on male and female patients over 40, diagnosed with IPF within five years of enrollment according to the most recent American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), Latin American Thoracic Association (ALAT) IPF guideline for diagnosis and management.

Diagnosis was assessed by central reviewers based on a combination of high resolution computerized tomography pattern and surgical lung biopsy if available. A diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin (HgB) of 30-79 percent of predicted normal and a FVC of greater than 50 percent of predicted normal were also required for enrollment.

Boehringer Ingelheim: Leading Respiratory Forward

Through research, treatments and patient-centric support services, the Boehringer Ingelheim (BI) lung health portfolio is designed to help address the challenges people living with a lung disease face every day. Leveraging the company's cutting edge science and leadership in chronic obstructive pulmonary disease (COPD), BI is researching new treatment approaches where needs persist. It is the company's goal to make a difference in the lives of patients with COPD, asthma, lung cancer, idiopathic pulmonary fibrosis and other respiratory diseases.

About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 44,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.

In 2011, Boehringer Ingelheim achieved net sales of about 13.2 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 23.5% of its net sales.

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Boehringer Ingelheim Pharmaceuticals, Inc.
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