Ofev Can Safely Treat Progressive Fibrosing ILDs in Japanese Patients

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by Vanda Pinto PhD |

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Ofev for Japanese patients | Pulmonary Fibrosis News | INBUILD trial subanalysis | trial data

With reasonable safety, Ofev (nintedanib) slowed lung function decline in Japanese patients with progressive fibrosing interstitial lung diseases (ILDs), according to a subgroup analysis of the Phase 3 INBUILD trial.

Overall, this analysis provides further assurance to clinicians in Japan on Ofev’s benefits to patients there, with “no new or unexpected safety findings” from previous trial analyses evident, its researchers said.

The study, “Efficacy and safety of nintedanib in Japanese patients with progressive fibrosing interstitial lung diseases: subgroup analysis of the randomised, double-blind, placebo-controlled, phase 3 INBUILD trial,” was published in the journal Respiratory Medicine.

Ofev, by Boehringer Ingelheim, is an oral anti-fibrotic therapy that lessens tissue scarring, or fibrosis, in the lungs, and widely approved to treat idiopathic pulmonary fibrosis (IPF), including in Japan. It is also approved in the U.S., Canada, and Europe to treat progressive fibrosing ILDs, a group of respiratory diseases characterized by progressive lung tissue scarring.

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The Phase 3 INBUILD trial (NCT02999178) tested Ofev’s efficacy and safety over 52 weeks at a 150 mg dose given twice daily in 663 people with progressive fibrosing ILDs other than IPF. Trial findings, released in 2019, showed that Ofev slowed the rate of disease progression relative to placebo-treated patients by slowing lung function decline by more than 50%.

Researchers now focused on Ofev’s efficacy and safety in a trial subgroup — 108 Japanese patients with progressive fibrosing ILDs — as compared with findings from the overall INBUILD study.

INBUILD, conducted in 15 countries from February 2017 to August 2019, randomized patients ages 18 and older (20 and older in Japan) to Ofev treatment or a placebo.

Its main goal was changes in the annual rate of lung function decline, as measured by forced vital capacity (FVC; the amount of air forcefully exhaled after a deep breath)  from baseline or study’s start to week 52.

Secondary goals included changes in health-related quality of life, as assessed by the King’s Brief Interstitial Lung Disease (K-BILD) questionnaire, and time-to-first acute ILD exacerbation (sudden symptom worsening) or death.

Japanese patients were slightly older and had a lower weight and body mass index (BMI), a measure of body fat, than non-Japanese patients in the trial, and 52 of these 108 people were treated with Ofev, while the remainder were randomized to placebo.

More Japanese that other trial patients were heavy smokers (40% vs. 22%), and more had signs of usual interstitial pneumonia on high-resolution computed tomography (HRCT) chest scans (78% vs. 59%). FVC values were similar between Japanese and non-Japanese patients.

Adjusted annual rates of FVC decline over 52 weeks were -148.31 milliliters per year (mL/year) for those given Ofev and -240.36 mL/year for those on a placebo. Among non-Japanese patients, these values were -67.41 mL/year for in the Ofev group and -177.65 mL/year for the placebo.

“Despite the differences in baseline clinical characteristics, the effect of nintedanib on efficacy endpoints in Japanese patients with progressive fibrosing ILDs was consistent with those of non-Japanese patients and the overall INBUILD population,” the scientists wrote.

No differences in changes in health-related quality of life measures were seen between Ofev-treated Japanese and non-Japanese patients by the study’s end.

Researchers also found that the risk of acute exacerbation or death was 30% lower in Japanese patients taking Ofev compared with those given a placebo. The risk of death was 54% lower in Ofev-treated Japanese patients.

Side effects, including severe ones, were similar among treated and placebo-group Japanese patients, the researchers reported. But as a group, Japanese patients in both study arms had higher rates of adverse events, including serious events, relative to the overall trial population, and these patients were more likely to leave the study due to adverse events than were non-Japanese patients.

Specifically, more adverse events (AEs) of any type were reported in Japanese patients relative to non-Japanese patients, and more treatment-related AEs were found in this group (90.4%) than among the non-Japanese patient group (76.8%). The most common treatment-related side effects were diarrhea and elevated liver enzymes, but treated Japanese patients also had greater evidence of “weight decreased, and decreased appetite” than did non-Japanese patients.

More Japanese patients also lowered their Ofev dose (44.2%) due to AEs during the study than did non-Japanese patients (31.1%), the researchers noted.

Still, these findings were similar to those seen in Japanese patients in other Ofev trials, with no new safety warnings evident.

“Although some AEs occurred more frequently compared with the overall INBUILD population, the safety profile of nintedanib was consistent with Japanese patients in previous trials of patients with IPF and SSc-ILD [Systemic sclerosis-ILD],” the researchers wrote.

“Collectively, these findings provide clinicians with assurances regarding the efficacy and safety of nintedanib in Japanese patients with progressive fibrosing ILDs,” they concluded.