Long-term treatment with Ofev (nintedanib) safely and effectively slows lung function decline in adults with interstitial lung disease (ILD) associated with systemic sclerosis (SSc-ILD), according to an early analysis of the SENSCIS-ON extension study.
Notably, patients treated with Ofev in both the Phase 3 SENSCIS trial (NCT02597933) and the ongoing extension study (NCT03313180) showed a steady, slower lung function decline over two years of treatment.
“With this new analysis, we now have data following patients for two years showing the impact of Ofev in reducing lung function decline and a consistent safety profile in patients with SSc-ILD,” Thomas Leonard, PhD, executive director of clinical development and medical affairs at Boehringer Ingelheim, Ofev’s developer, said in a press release.
“These new data add to the important body of evidence for Ofev and the role it plays for patients with SSc-ILD,” he added.
The findings, “Continued Treatment with Nintedanib in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD): Interim Analysis of SENSCIS-ON,” were recently presented at the 2020 American College of Rheumatology Convergence virtual meeting.
Ofev is the first and only therapy approved to slow lung function decline in people with SSc-ILD. Interstitial lung disease, a group of lung disorders that affect breathing and impair the lungs’ ability to transfer oxygen to the bloodstream, is the leading cause of death in people with SSc, or scleroderma.
Given through an oral capsule, Ofev works by blocking a group of growth factor receptors involved in lung fibrosis, or scarring.
Its approval was based on top-line data from the global SENSCIS study, which showed that one year of treatment was superior to a placebo at slowing lung function decline — as assessed through forced vital capacity (FVC) — in 576 adults with SSc-ILD.
Notably, FVC represents the volume of air in the lungs that can be exhaled after a deeply inhaled breath; it is typically presented as a percentage of a reference value, but can also be represented in liters of air volume.
Specifically, Ofev-treated patients showed a 44% slower lung function decline over one year, compared with those on a placebo. Additional analyses showed that the therapy was also superior to placebo at preventing certain degrees of lung function decline considered to be clinically meaningful.
Ofev was generally well-tolerated, with a safety profile consistent with previous trials.
Patients completing SENSCIS had the option to enter the SENSCIS-ON extension study, in which all would continue or initiate Ofev treatment for nearly three years.
About 74% of SENSCIS participants enrolled in SENSCIS-ON: 197 patients treated with Ofev (continued Ofev group) and 231 initially assigned to a placebo (Ofev initiation group).
Sixteen women with SSc-ILD who completed up to 28 days of Ofev treatment in another trial (NCT03675581) were also enrolled in the extension study, and included in the Ofev initiation group.
SENSCIS-ON’s goals are to assess Ofev’s long-term safety and effectiveness (through changes in FVC).
The interim analysis included the 347 patients still on Ofev after one year in the extension trial: 176 in the continued Ofev group and 171 in the Ofev initiation group.
Results showed that these patients had a decrease in lung function (mean FVC annual change of 51.3 mL) comparable to that reported at one year for Ofev-treated patients in SENSCIS (FVC change of 42.7 mL).
In particular, the mean FVC change over one year of treatment was 58.3 mL for those who had been on Ofev for a total of two years, and 44 mL for those in the Ofev initiation group.
Ofev’s safety profile was consistent with that reported in the SENSCIS study, with diarrhea being the most frequent adverse event (in about 68% of patients).
Compared with participants in the continued Ofev group, more patients initiating Ofev in SENSCIS-ON discontinued treatment due to adverse events — 53 patients (21.5%) vs. nine (4.6%) — and showed abnormally high levels of liver enzymes, a marker of liver damage (20 patients or 8.1% initiating therapy vs. three patients or 1.5% on continued therapy).
These proportions of patients treated for two years were lower than those reported in their first year of treatment in SENSCIS — 16% for adverse event-related treatment discontinuations and 4.9% for increases in liver damage markers.
Overall, the data showed that the safety and effectiveness of Ofev over one year in the extension study was comparable to that reported for patients treated for one year in SENSCIS.
“These findings support a clinically meaningful benefit of [Ofev] in slowing the progression of SSc-ILD,” the researchers wrote in the session’s abstract.
The data also showed that 4%–6% of patients presented with ILD one year before their SSc diagnosis.
“These findings confirm that interstitial lung disease can present early in the course of SSc,” said Shervin Assassi, MD, director of the rheumatology division at The University of Texas, in Houston. “These data are consistent with other studies and reinforce the need to examine SSc patients early for pulmonary involvement.”