Progressive fibrosis of the lung can have a devastating impact on patients with a range of conditions.
Except for idiopathic pulmonary fibrosis ( IPF ) and the new approved therapy for use in scleroderma-associated interstitial lung disease ( SSc-ILD ) in the U.S., there are currently no medications approved for the treatment of progressive fibrosing ILDs.
The results of INBUILD have shown for the first time that Nintedanib ( Ofev ) has slowed the decline of lung function in patients with a range of fibrosing lung diseases, who demonstrate a progressive phenotype, across a spectrum of interstitial lung disease ( ILD ) diagnoses.

The INBUILD trial was a randomised, double-blind, placebo-controlled, parallel group trial conducted at 153 sites in 15 countries that evaluated the efficacy, safety, and tolerability of Nintedanib ( 150 mg, 2 x daily ) over 52 weeks in patients with progressive fibrosing interstitial lung disease.
Eligible patients were aged greater than or equal to 18 years with a physician-diagnosed ILD other than IPF and features of fibrosing lung disease of more than 10% extent in high-resolution computed tomography ( HRCT ).
Patients were required to meet criteria for ILD progression within 24 months before screening, based on decline in FVC ( forced vital capacity ), increased fibrotic changes on imaging, or worsening of symptoms, despite treatment with drugs commonly used in clinical practice to treat ILD.

A total of 663 patients, of whom 412 ( 62.1% ) had a usual interstitial pneumonia ( UIP ) fibrotic pattern on HRCT, were randomised 1:1 to receive oral Nintedanib 150 mg twice daily or placebo.

The primary endpoint was the annual rate of decline in FVC ( mL/year ) assessed over 52 weeks.
FVC is a lung function test measuring the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
As fibrosis progresses, lung function gradually and irreversibly deteriorates.
Main secondary endpoints were absolute change from baseline in King’s Brief Interstitial Lung Disease ( K-BILD ) questionnaire total score at week 52, time to first acute exacerbation of ILD or death over 52 weeks; and time to death over 52 weeks.
An acute exacerbation is a sudden clinically significant deterioration in respiratory function, in many cases with unknown cause, which negatively impacts the disease course and often leads to death.

In progressive fibrosing interstitial lung disease, the course of the disease and the symptoms are similar in progressive fibrosing interstitial lung diseases regardless of the underlying condition.
There is an accelerated loss of lung function, a deterioration in quality of life and the disease is associated with a poor prognosis.

The progressive fibrosis of the lung leads to an irreversible loss of lung function and is associated with high morbidity and mortality.
On average, 18-32% of patients with ILD might develop a progressive pulmonary fibrosis.
Progressive fibrosing interstitial lung diseases encompass a range of clinical diagnoses, including: hypersensitivity pneumonitis, sarcoidosis, autoimmune ILDs such as rheumatoid arthritis-associated ILD, systemic sclerosis-associated ILD, mixed connective tissues disease-associated ILD, idiopathic non-specific interstitial pneumonia, and unclassified idiopathic interstitial pneumonia amongst others.

Nintedanib is already approved for the treatment of patients living with idiopathic pulmonary fibrosis.

In September 2019, Nintedanib was approved in the U.S. as the first and only therapy to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated ILD. ( Xagena_2019 )

Source: Boehringer Ingelheim, 2019

Xagena_Medicine_2019