INMARK results suggest prompt treatment of IPF with antifibrotics to slow disease progression

On Jul 19, 2019

Results from the INMARK study, a randomised, double-blind clinical trial of Ofev (nintedanib) vs. placebo (12 weeks) followed by an open label period (40 weeks) in patients with idiopathic pulmonary fibrosis (IPF) were published on 17 July 2019 in The Lancet Respiratory Medicine. INMARK was the first clinical trial to investigate the predictive value of biomarkers in IPF patients treated with an antifibrotic (nintedanib). Study results reinforce the evidence that even in patients with very well-preserved lung function, a difference in forced vital capacity (FVC) decline could be demonstrated between patients treated with nintedanib and placebo over 12 weeks of treatment.

IPF is a rare, debilitating and fatal lung disease which affects approximately 3 million people worldwide. It causes progressive scarring of the lungs, resulting in continual and irreversible deterioration in lung function and breathing difficulties. Due to the unpredictable nature of IPF and that the loss of lung function is irreversible, experts believe that treatment should be considered and offered to patients promptly.

INMARK assessed the rate of change in CRPM, a biomarker that has been previously shown to be predictive of mortality in IPF, from baseline to week 12 and the proportion of subjects with disease progression defined as an absolute decline in FVC ≥10% predicted or death over 52 weeks.

Treatment with nintedanib versus placebo for 12 weeks did not affect the rate of change in CRPM but was associated with a reduced rate of decline in FVC.

29% of the subjects in this trial experienced an FVC decline of ≥10% predicted or died over 52 weeks of follow-up, highlighting the progressive nature of IPF also in this population with FVC ≥80% predicted.

Over 12 weeks, there was a lower rate of FVC decline in patients treated with nintedanib versus placebo (5.9 (18.5) mL/12 weeks in the nintedanib group and −70.2 (13.1) mL/12 weeks in the placebo group).

“Even in this population of patients with very well-preserved lung function, a difference in FVC decline could be demonstrated between patients treated with nintedanib vs. placebo over 12 weeks of treatment. Considering the unpredictable nature of IPF and the fact that loss of lung function is irreversible the results reinforce a growing body of evidence that early treatment of IPF is the best course of action.” commented Prof Toby Maher, Consultant Respiratory Physician at the Royal Brompton Hospital in London, United Kingdom and principle investigator of the study.

Dr. Susanne Stowasser, Associate Head of Medicine Respiratory at Boehringer Ingelheim, said “Biomarker research is a key driver of modern medicine with huge impact on the understanding of health and disease states, diagnosis, drug development, and prediction of disease course or response to therapy. INMARK was the first clinical trial to investigate the predictive value of biomarkers in IPF patients treated with an antifibrotic. Being poorly understood, IPF has been subject of increasing biomarker research for years with a main focus on identifying markers for prognosis.” She added: “Pulmonary Fibrosis continue to have a devastating impact on people’s lives. Boehringer Ingelheim is committed to research such as the INMARK trial which helps our understanding of how interstitial lung diseases such as IPF progress in individual patients, and identify those who may respond best to treatment.”