Boehringer Ingelheim Pharmaceuticals recently began a clinical trial to assess the effect of Ofev (nintedanib) on specific blood biomarkers that may identify greater fibrosis and loss of lung function in patients with idiopathic pulmonary fibrosis (IPF).
Biomarkers are measurable indicators of some biological state or condition that help predict disease prognosis. The INMARK trial will measure biomarkers that reflect substances related with extracellular matrix (ECM) turnover — part of healthy tissue maintenance.
But excessive or uncontrolled turnover motivates the structural change seen in the lungs of patients with IPF, and that leads to progressive scarring and loss of lung function.
By evaluating baseline changes and values, it may be possible to determine patients with most active fibrosis, and determine the response to Ofev treatment. Additionally, correlating biomarker concentrations with final lung function assessments may identify early predictors for pulmonary progression.
IPF is a rare, debilitating, and fatal disorder in which the lungs become progressively scarred over time. As a result, patients with IPF experience shortness of breath, cough, and have difficulty participating in everyday physical activities. The most common interstitial lung disease worldwide, IPF affects an estimated three million people and poses a major public health threat.
The IPF median survival rate is two to three years after diagnosis; up to 80% of patients succumb to the disease within five years of diagnosis. Currently, despite recent progress, the cause of IPF is unidentified and treatment is limited.
“Despite advances in IPF, physicians are still uncertain when to start treatment because there are differences in disease progression across IPF patients. Biomarkers may inform us on how the disease will progress in Ofev-treated patients and identify earlier response prior to showing definitive pulmonary function changes,” said Dr. Imre Noth, professor and director of the Interstitial Lung Disease Program at the University of Chicago, in a press release.
Dr. Martina Flammer, vice president of Clinical Development & Medical Affairs Specialty Care for Boehringer Ingelheim Pharmaceuticals said the company is proud to initiate the first study to investigate the effects of an IPF treatment on biomarkers that may be predictive of IPF progression.
“In a disease that displays variable rates of progression, identification of biomarkers that could allow physicians to identify and monitor individual disease progression and treatment successes in patients with IPF is essential. We hope that the identification of these biomarkers, particularly early in the disease, has the potential to improve treatment and enable better delivery of patient care,” Flammer said.
Ofev inhibits tyrosine kinase, an enzyme essential for signal transduction pathways that trigger growth factors like vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet derived growth factor receptor (PDGFR) which are secreted in excess amounts in patients with IPF.
The growth factors promote collagen production and deposition, and help in the differentiation, maturation, and proliferation of the fibroblasts which eventually lead to the formation of scar tissues in the lungs.
Nintedanib binds to the phosphorylating site of tyrosine kinase, which blocks the cell signaling mechanism and slows the progression of the disease.
INMARK is one of many current Boehringer Ingelheim trials collecting safety data for Ofev in combination with other drugs and across different patient populations.