Ofev (nintedanib) slows clinically relevant disease progression in adults with interstitial lung disease (ILD) associated with systemic sclerosis (SSc-ILD), according to an exploratory analysis of the Phase 3 SENSCIS trial.
These new results, combined with the trial’s top-line data, which showed that Ofev significantly slowed the annual rate of lung function decline in people with SSc-ILD, support the therapy’s benefits in this patient population.
The findings were reported in the study, “Effect of nintedanib on lung function in patients with systemic sclerosis‐associated interstitial lung disease: further analyses of the SENSCIS trial,” published in the journal Arthritis & Rheumatology.
It is estimated that one-quarter of people with SSc develop scars in the lungs within the first three years following diagnosis. That can lead to ILD, the leading cause of death among these patients.
ILD is a group of lung disorders in which the tissue in and around the lung air sacs — called the interstitium — becomes inflamed and scarred, affecting breathing and impairing lungs’ ability to transfer oxygen to the bloodstream.
Marketed by Boehringer Ingelheim, Ofev is a small molecule that works by blocking a group of growth factor receptors involved in lung fibrosis, or scarring. It was approved in the U.S. in 2014 for the treatment of idiopathic pulmonary fibrosis (IPF), the most common ILD — a decision followed by regulatory agencies in more than 70 countries.
Last year, Ofev became the first therapy approved to slow lung function decline in people with SSc-ILD. Its September 2019 approval was based on data from the global Phase 3 SENSCIS trial (NCT02597933), which evaluated Ofev’s safety and effectiveness in 576 adults with SSc-ILD.
The participants, with a mean age of 54 years, were randomly assigned to receive an oral capsule of either Ofev (288 patients) or a placebo (288 patients), twice daily, for at least a year (52 weeks).
Top-line results showed Ofev slowed patients’ lung function decline — as assessed through forced vital capacity (FVC) — by 44% over one year, compared with a placebo, meeting the trial’s main goal. Of note, FVC represents the total volume of air in the lungs that can be exhaled after a deeply inhaled breath; it is often presented as a percentage of a reference value (normally above 80%).
The therapy also was generally well tolerated, with a safety profile consistent with that reported in previous trials.
Now, the SENSCIS researchers set out to assess whether Ofev also was superior to the placebo at preventing certain degrees of lung function decline considered to be clinically meaningful.
These included FVC thresholds for minimal clinically important changes reflecting improvement (an increase of at least 3%) and worsening (a drop of 3.3% or greater), as well as FVC declines of 5–10% and 10–15%.
Drops greater than 10% in FVC previously have been used as a marker of clinically relevant ILD progression, “based on the association between decline in FVC and mortality,” the researchers wrote.
The team also assessed the risk of lung function decline or death. Lung function decline was determined by an FVC drop of at least a 5% or 10%, or a 5–9.9% FVC decline and a 15% or greater drop in the diffusing capacity of the lungs for carbon monoxide, known as DLCO. Of note, DLCO measures how much oxygen travels from the lungs to the bloodstream.
A total of 46 (16%) patients in the Ofev group and 31 (10.8%) in the placebo had no FVC data at one year, and were therefore not included in the exploratory analysis.
The results showed that 55.7% of patients receiving Ofev and 66.3% of those on a placebo had a decline in FVC after one year of treatment.
However, a smaller proportion of Ofev-treated patients showed clinically relevant FVC worsening (34.5% vs. 43.8%), and a decline of 5–10% (13.6% vs. 20.1%) and 10–15% (3.5% vs. 5.2%), compared with those given a placebo.
Patients in the Ofev group also were more likely to show clinically relevant FVC improvements than those on a placebo (23% vs. 14.9%).
Moreover, compared with a placebo, Ofev significantly lowered patients’ risk of lung function decline or death by 36% when considering an FCV decline of 10% or greater, and by 42% when considering both an FVC drop of at least 10% or a decline of 5–9.9% with a 15% DLCO drop.
Further analysis showed the proportion of patients meeting proposed FVC thresholds for worsening or improvement was consistent between groups for a number of potentially influencing factors, highlighting the strength of the results.
“In conclusion, these further analyses of FVC decline in the SENSCIS trial support a clinically meaningful effect of nintedanib on slowing the progression of SSc-ILD,” the researchers wrote, noting the findings were consistent with those previously reported in IPF patients.
An open-label extension study (NCT03313180) is now ongoing to evaluate Ofev’s long-term safety in 444 SSc-ILD patients over nearly three years.
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