Ofev Reduces Lung Function Decline in Patients with Fibrotic Lung Diseases, Phase 3 Trial Shows

Ofev (nintedanib) reduced lung function decline by more than 50% in patients with progressive fibrosing interstitial lung diseases (ILDs), data from a Phase 3 trial show.

The findings were presented in a poster at the recent European Respiratory Society (ERS) International Congress in Madrid, Spain, and simultaneously published in the New England Journal of Medicine.

ILDs comprise a group of more than 200 disorders, including pulmonary fibrosis — a condition in which the lungs become irreversibly scarred and cease to work properly.

Ofev is an approved anti-fibrotic therapy (medication that reduces lung tissue scarring), marketed by Boehringer Ingelheim, for the treatment of idiopathic pulmonary fibrosis (IPF) and scleroderma. The medication works by interfering with the PDGF and FGF signaling pathways, which are known to be overly active in patients with lung fibrosis (scarring).

The effects of Ofev in patients with progressive fibrosing ILDs, other than IPF, were investigated in the randomized, double-blind, placebo-controlled, Phase 3 INBUILD trial (NCT02999178).

The study, sponsored by Boehringer Ingelheim, enrolled a total of 663 adult patients who were randomly assigned to receive either Ofev (administered at a dose of 150 mg twice-a-day), or a placebo, for a period of one year (52 weeks).

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The trial’s primary endpoint was to determine the annual rate of lung function decline by measuring changes from baseline to week 52 in patients’ forced vital capacity (FVC, the amount of air a patient is able to exhale after taking a deep breath).

Secondary endpoints included assessing changes from baseline to week 52 in the participants’ health-related quality of life, using the King’s Brief Interstitial Lung Disease (KBILD) questionnaire; the time patients lived until experiencing an acute exacerbation or death; showing signs of disease progression; and dying due to any cause or due to a respiratory complication.

Findings from INBUILD showed that the study met its primary endpoint, with Ofev reducing patients’ lung function decline by 57% over the course of one year compared with the placebo — FVC reduction of 80.8 mL/year for Ofev versus 187.8 mL/year for the placebo, a difference of 107 mL per year.

Importantly, data revealed that Ofev slowed the rate of disease progression in all patients, regardless of the lung tissue scarring pattern seen in high-resolution computed tomography chest scans.

“In patients with progressive fibrosing interstitial lung diseases, the annual rate of decline in the FVC was significantly lower among patients who received nintedanib [Ofev] than among those who received placebo,” the researchers wrote.

Secondary endpoints also showed positive trends. Over the course of one year, patients who had been treated with Ofev experienced a mild improvement in their health-related quality of life, unlike those treated with a placebo (KBILD scores of 0.55 versus -0.79).

Moreover, Ofev also reduced the percentage of patients experiencing an acute exacerbation or death during the study period (7.8% versus 9.7% in the placebo group), as well as the percentage of patients who died due to any cause during the study period (4.8% versus 5.1% with the placebo).

The most common adverse event seen during the trial was diarrhea, which was more frequent among patients treated with Ofev (66.9%) than among those treated with the placebo (23.9%). This finding was consistent with observations from previous studies.

Other side effects, including nausea, vomiting, abdominal pain, decreased appetite, and weight loss, were also more common among patients treated with Ofev. In addition, the treatment was associated with an increase in the levels of certain liver enzymes, which were easily resolved by dose adjustments, treatment interruption, or spontaneously.

“Progressive fibrosis of the lung can have a devastating impact on patients with a range of conditions. Yet, except for IPF and the new approved therapy for use in SSc-ILD [scleroderma-associated ILD] in the U.S., there are currently no medications approved for the treatment of progressive fibrosing ILDs,” Kevin Flaherty, MD, professor in the division of pulmonary and critical care medicine at the University of Michigan in Ann Arbor, and lead investigator of the INBUILD trial, said in a news release.

“The results of INBUILD showed for the first time that nintedanib [Ofev] slowed the decline of lung function in patients with a range of fibrosing lung diseases who demonstrate a progressive phenotype [symptoms] across a spectrum of ILD diagnoses,” Flaherty added.

Based on these results, Boehringer recently submitted regulatory applications for Ofev to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

“We are very proud to be presenting the results of this first ever clinical trial studying patients with different forms of progressive fibrosing ILDs, which are the basis of the regulatory applications that were recently submitted with the FDA and EMA,” said Mehdi Shahidi, MD, chief medical officer of Boehringer Ingelheim.

“We are absolutely committed to improving the lives of people living with pulmonary fibrosis, in particular those affected by rare diseases with a high level of unmet need,” he said.