Ofev Slows Lung Function Decline in SSc-ILD Patients, Analysis of Phase 3 Study Shows

Treatment with Ofev (nintedanib) slows the rate of lung function decline in people with autoimmune-related interstitial lung diseases (ILDs), including scleroderma, a new analysis shows.

Those are the results of the global Phase 3 INBUILD study (NCT02999178), which evaluated the therapeutic benefits of Ofev in people with ILDs with progressive fibrosis, or scarring.

The research, “The INBUILD Trial of Nintedanib in Patients with Progressive Fibrosing Interstitial Lung Diseases: Subgroup with Autoimmune Diseases,” was presented at the 2019 American College of Rheumatology and the Association of Rheumatology Professionals (ACR/ARP) Annual Meeting, being held Nov. 8-13 in Atlanta.

ILD is a group of disorders characterized by inflammation and scarring in the tissue in and around the pulmonary air sacs (alveoli), impairing the lungs’ ability to transfer oxygen to the bloodstream.

In people with scleroderma — or systemic sclerosis, SSc — the development of ILD is associated with aggravated symptoms and worse outcomes.

Boehringer Ingelheim’s Ofev is an anti-fibrotic therapy approved in more than 70 countries for treating people with idiopathic pulmonary fibrosis (IPF). It was recently approved in the U.S. for those with SSc-ILD.

However, there are no approved treatments for people with a broad range of other progressive fibrosing ILDs.

The Boehringer-sponsored INBUILD study evaluated the safety and effectiveness of Ofev in 663 people with progressive fibrosing ILDs, other than IPF. Participants were randomly assigned to receive either 150 mg of Ofev or a placebo twice daily for a year.

INBUILD was the first clinical trial in ILDs to group participants based on the clinical characteristics of their disease rather than on their primary clinical diagnosis.

The trial’s primary goal was to assess whether Ofev slowed lung function decline, as measured by the annual rate of decline in forced vital capacity (FVC) — the total volume of air that can be exhaled following a full inhalation.

Treatment with Ofev significantly slowed lung function decline — 57% less than with a placebo — over one year of treatment, as reported previously. Ofev’s safety profile was consistent with that reported in previous clinical trials.

Those findings supported Boehringer’s submission of a supplemental new drug application covering Ofev as a treatment for progressive fibrosing ILD. That application is currently under review by the U.S. Food and Drug Administration (FDA). Ofev recently received breakthrough therapy designation from the FDA as a potential treatment for progressive fibrosing ILD.

A new analysis of the INBUILD data now shows that Ofev induced similar benefits in people with progressive fibrosis ILD that is specifically associated with autoimmune diseases, including scleroderma.

“Results from this analysis provide further insights into [Ofev]’s effect on the rate of lung function decline in patients with fibrotic [ILDs] irrespective of their primary clinical diagnosis,” Eric Matteson, MD, the study’s presenter and and an emeritus professor at Mayo Clinic College of Medicine and Science, said in a press release.

This new analysis involved 171 patients with autoimmune-related ILDs (25.8% of all participants). Rheumatoid arthritis-associated ILD (88 patients), SSc-ILD (40 patients), and mixed connective tissue disease-associated ILD (20 patients) were the most common.

Among the 40 participants with SSc-ILD, 60% were white and the mean age was 58.6 years. At the beginning of the study, these individuals had a mean 69.5% of predicted FVC and a mean 53.2% of predicted diffusion capacity of the lungs for carbon monoxide (DLCO), a measure of oxygen uptake.

Half of these patients had at least a 10% relative decline in FVC in the two years before screening and 24 (60%) had an usual interstitial pneumonia (UIP)-like fibrotic pattern — which was most commonly found in patients with rheumatoid arthritis-related ILD (87.5%). An UIP pattern consists of specific changes in the structure of lung tissue due to chronic scarring.

Compared with the other groups, people with SSc-ILD had the poorest lung function, but the highest values of DLCO before treatment initiation.

At the ACR/ARP meeting, the company is presenting 11 other studies on Ofev in SSc-ILD and fibrosing ILDs.

“As a leader in the field of ILD research, we are fully committed to better understand how to treat these devastating diseases,” said Thomas Leonard, PhD, executive director of clinical development and medical affairs, specialty care at Boehringer.

“The abstracts being presented at the 2019 ACR/ARP Annual Meeting offer a better understanding of nintedanib’s effect across a variety of patients with fibrotic ILDs,” Leonard said.