IPF Patients Treated With Nintedanib (Ofev) More Likely To Have Stable Lung Function

MedicalResearch.com Interview with:

Kevin R. Flaherty

Dr. Flaherty

Kevin R. Flaherty, M.D., M.S.
Professor, Department of Internal Medicine
Associate Director, T32 Multidisciplinary Training Program in Lung Diseases
Chair, Pulmonary Fibrosis Foundation Clinical Care Network Steering Committee
University of Michigan Medicine 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This is a new post-hoc analysis, recently presented at the 2017 American Thoracic Society (ATS) conference, which sought to further assess the efficacy of Ofev (nintedanib), an FDA-approved drug treatment for idiopathic pulmonary fibrosis (IPF), and its effect on lung function in those with this disease.

IPF is a rare and serious lung disease that causes permanent scarring of the lungs and affects as many as 132,000 Americans.

The analysis examined pooled data from the two placebo-controlled, global Phase III INPULSIS trials, which evaluated the efficacy and safety of 52 weeks’ treatment with nintedanib in people with IPF. In both trials, a higher proportion of people treated with placebo than nintedanib had disease progression from baseline to week 52, as defined by the proportions of patients with ≥5% or ≥10% declines in lung function, as measured by forced vital capacity (FVC) % predicted. Additionally, a lower proportion of patients treated with placebo than nintedanib had no decline or an improvement in FVC % predicted.

These data support the initial findings from the Phase III INPULSIS trials which found that more patients treated with nintedanib versus placebo had an absolute decline in FVC of less than 5%.

In this subgroup analysis, we assessed the proportions of patients from the two INPULSIS trials treated with nintedanib and placebo who had no decline or an improvement in lung function from baseline to week 52 using pooled data for this post-hoc analysis. In terms of those who participated, a total of 864 patients were included (519 treated with nintedanib, 345 treated with placebo). Baseline characteristics including age, gender and FVC were similar between the subgroups of patients who had no decline or an improvement in FVC and those whose FVC declined, and between the nintedanib and placebo groups within each subgroup.

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T Cell Biomarkers Predictive of Course of IPF – Idiopathic Pulmonary Fibrosis

MedicalResearch.com Interview with:

Catherine Bonham MD Section of Pulmonary and Critical Care Medicine University of Chicago

Dr. Bonham

Catherine Bonham MD
Section of Pulmonary and Critical Care Medicine
University of Chicago

MedicalResearch.com: What is the background for this study?

Response: Idiopathic pulmonary fibrosis (IPF) causes fibrosis, or scar tissue, to form in the lungs. People with IPF become more and more short of breath and need oxygen. It is progressive and we don’t have any cure. Prognosis is about 3 to 5 years, worse than many cancers. We don’t know what causes it. It is a leading indication for lung transplant.

Many doctors and scientists are skeptical about the role of the immune system in IPF because some immune-directed treatments, like steroids, have been tried and failed. However, recent research shows that the expression of genes in patients who do well with IPF is different from patients who do poorly and die rapidly from IPF. The difference in survival was in genes expressed by their immune systems, specifically their T cells. We have known for decades that T cells are a type of white blood cell specialized for fighting infection. In the last several years, doctors and scientists made the amazing discovery that T cells also fight cancer within the body. Many new immune therapies have now been developed that can make some patients cancer-free. It was very exciting to think that T cells could also affect survival in pulmonary fibrosis.

My study followed 59 patients with Idiopathic pulmonary fibrosis for up to 5 years, and examined whether we could measure two molecules on the surface of CD4 T cells, and use them to predict survival for patients with IPF. These molecules are called ICOS and CD28. They function to activate the T cells, which creates a chain reaction activating other parts of the immune system.

A second part of my study looked at the lungs and lymph nodes from 9 IPF patients who generously donated their old lungs to research after they received lung transplant. The purpose of this was to find if what I see in blood samples reflected what the T cells really do in the lungs.

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First Patients Enrolled in Study of Nintedanib For Progressive Fibrosing Lung Conditions

MedicalResearch.com Interview with:

Thomas Leonard, Ph.D. Executive director, Clinical Development and Medical Affairs, Specialty Care Boehringer Ingelheim Pharmaceuticals, Inc.

Dr. Thomas Leonard

Thomas Leonard, Ph.D.
Executive director, Clinical Development and Medical Affairs, Specialty Care
Boehringer Ingelheim Pharmaceuticals, Inc.

MedicalResearch.com: What is the background for this study? Would you tell us a little more about IPF?

Response: Boehringer Ingelheim’s Phase III PF-ILD (progressive fibrosing interstitial lung disease) trial will investigate the safety and efficacy of nintedanib, in a range of progressive fibrosing lung conditions other than idiopathic pulmonary fibrosis, or IPF. The PF-ILD trial is the first time that patients with different fibrosing lung diseases will be included in one single clinical trial assessing the efficacy of nintedanib as a potential treatment, and the trial is the first in the field of fibrosing lung diseases to group patients based on the clinical characteristics of their disease, rather than the diagnosis.

There are more than 200 conditions that affect the tissue and space around the air sacs of the lungs, or interstitium, and, collectively, these conditions are called interstitial lung diseases — or ILDs. Based on clinical observations, there is a group of patients with ILD who, independent from the classification of the ILD, exhibit progressive fibrosis. The proposed terminology for describing this group of patients is PF-ILD. In these patients, the disease appears to follow a course similar to IPF with worsening of respiratory symptoms, lung function, quality of life and ability to perform daily activities, as well as early mortality despite treatment.

There is currently no efficacious treatment available for PF-ILD. This trial is exploring how fibrosis in the lungs is treated and whether nintedanib is a potential treatment, based on the efficacy and safety of nintedanib in IPF, a rare and serious lung disease that causes permanent scarring of the lungs, making it difficult to breathe. IPF affects as many as 132,000 Americans, typically men over the age of 65. On average, people with IPF live only three to five years after diagnosis, and approximately 40,000 people die from this disease every year.

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Bernie Williams Discusses His Dad’s Journey With IPF and New Treatment Options

MedicalResearch.com Interview with:

Mr. Bernie Williams Four-time World Series champion and star centerfielder for the New York Yankees discusses his beloved dad Bernabé’s struggle with a rare lung disease called idiopathic pulmonary fibrosis (IPF)

Mr. Bernie Williams

Mr. Bernie Williams

Four-time World Series champion and star centerfielder for the New York Yankees discusses his beloved dad Bernabé’s struggle with a rare lung disease called idiopathic pulmonary fibrosis (IPF) 


MedicalResearch.com: Would you briefly explain what idiopathic pulmonary fibrosis is? How does it affect a person’s health and ability to breathe?

Mr. Williams: IPF is a rare and serious lung disease that causes permanent scarring of the lungs, and makes it difficult to breathe. Symptoms of IPF include breathlessness during activity, a dry and persistent cough, chest discomfort, fatigue and weakness. Although considered “rare,” IPF affects up to 132,000 Americans, and about 50,000 people in the U.S. are diagnosed every year with IPF – enough to fill a baseball stadium.

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Studies Reinforce Efficacy of Ofev in Idiopathic Pulmonary Fibrosis

MedicalResearch.com Interview with:

Dr. Luca Richeldi MD PhD Professor of Respiratory Medicine Chair of Interstitial Lung Disease University of Southampton United Kingdom

Dr. Luca Richeldi

Dr. Luca Richeldi MD PhD
Professor of Respiratory Medicine
Chair of Interstitial Lung Disease
University of Southampton
United Kingdom

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The data presented at CHEST 2016 were from two post-hoc pooled analyses of the Phase III INPULSIS® trials that evaluated Ofev in idiopathic pulmonary fibrosis, or IPF. Both analyses, using different measures, demonstrate Ofev efficacy in a range of people with IPF, regardless of disease severity at the start of the trials.

One analyses investigated the efficacy of Ofev on disease progression in subgroups of patients defined by their GAP (gender, age, physiology) stage. Based on the index, patients were categorized as either GAP stage I or II/III. The analysis showed a similar reduction in disease progression with Ofev versus placebo regardless of GAP stage – meaning no significant difference between GAP stage I versus GAP stage II/III. Disease progression was defined as an absolute decline in forced vital capacity (FVC) ≥5% predicted or death over 52 weeks.

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New Study Does Not Support Antacids for All Patients With IPF

MedicalResearch.com Interview with:

Prof Michael Kreuter Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg and Translational Lung Research Center Heidelberg, Germany

Dr. Michael Kreuter

Prof Michael Kreuter
Center for Interstitial and Rare Lung Diseases,
Pneumology and Respiratory Critical Care Medicine,
Thoraxklinik, University of Heidelberg and Translational Lung Research Center
Heidelberg, Germany

MedicalResearch.com: What is the background for this study? What are the main findings?

Prof. Kreuter: Already in the 70s, early reports hypothesized a relationship between gastroesophageal reflux disease (GERD) and pulmonary fibrosis (IPF). Since then, clinical and preclinical data suggested that micro-aspirations cause lung parenchymal injuries which may stimulate pulmonary fibrosis.

The hypothesis of a potential relationship between idiopathic pulmonary fibrosis (IPF_ and GERD also provoked the question of an effect of GERD-treatment by antacid therapy (i.e. proton pump inhibitors or H2-blockers) on the course of IPF.  In this context, two analyses, one retrospective and one post hoc, reported that antacid treatment had positive effects on the course of pulmonary function and on survival in IPF patients. These data lead to a conditional recommendation for the treatment of patients with IPF with antacid therapy in the current international IPF guideline.

However, the low confidence in estimates of the effect prompted us to initiate a new post-hoc analysis pooling data from the placebo arms of three multinational trials on pirfenidone in interstitial pulmonary fibrosis. In this new analysis, published in Lancet Respiratory Medicine, antacid therapy was not associated with a slower disease progression in IPF. Moreover, in patients with advanced disease antacid therapy was associated with a significantly higher incidence of pulmonary and non-pulmonary infections.

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Kinase Inhibitor Ofev Slows Progression of Idiopathic Pulmonary ibrosis

MedicalResearch.com Interview with –
Professor Luca Richeldi
University Hospital, Southampton
Southampton, UK

MedicalResearch.com: What is the background for this study? What are the main findings?

Prof. Richeldi: The pooled analysis published in Respiratory Medicine is based on Ofev (nintedanib) data from the Phase II TOMORROW trial and the two Phase III INPULSIS studies, and a total of 1,231 patients with idiopathic pulmonary fibrosis (IPF), 723 of whom were treated with Ofev. The results of this analysis confirm that Ofev significantly slows disease progression by approximately 50%, as measured by decline in forced vital capacity (FVC) across a range of patient types in the clinical trial program. In addition, the analysis confirms that Ofev reduces the risk of acute exacerbations by approximately 50% and has a favorable effect across mortality outcomes with a trend in lower all-cause mortality and a significant lower on-treatment-mortality.

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