Lysophosphatidic acid receptor 1 antagonist slows time to disease progression in IPF
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Key takeaways:
- Disease progression occurred in more patients receiving placebo vs. an oral lysophosphatidic acid receptor 1 antagonist.
- Recruitment for a phase 3 trial that further assesses this drug is in progress.
SAN DIEGO — Taking an oral lysophosphatidic acid receptor 1 antagonist for 26 weeks slowed time to disease progression in idiopathic pulmonary fibrosis, according to a presentation at the American Thoracic Society International Conference.
“These analyses provide additional evidence of the potential of BMS-986278, a first-in-class, oral, small molecule lysophosphatidic acid receptor 1 (LPA1) antagonist, as a meaningful therapeutic option for people living with pulmonary fibrosis,” Alyssa Johnsen, MD, PhD, senior vice president and head of clinical development of immunology, cardiovascular and neuroscience at Bristol Myers Squibb, told Healio.
As Healio previously reported, researchers of a phase 2 randomized controlled trial observed that receiving BMS-986278 (Bristol Myers Squibb) for 26 weeks lowered the rate of percent-predicted FVC decline in progressive pulmonary fibrosis. Similar results were found in a patient population with IPF.
In a post hoc analysis of the IPF trial, Michael Kreuter, MD, director of the Mainz Lung Center of the University Medical Center and the Marienhaus Clinic Mainz, and colleagues evaluated 225 patients (baseline median FVC, 77.25% predicted) with IPF to compare time to first disease progression event between those receiving twice-daily 30 mg BMS-986278 (n = 82) or 60 mg BMS-986278 (n = 84) vs. placebo (n = 89) at 26 weeks.
Outcomes classified as disease progression events included all-cause mortality, all-cause hospitalization, acute exacerbation and at least 10% decline in relative percent-predicted FVC, according to researchers.
Notably, researchers counted multiple events that took place on the same day as one event but reported it as whichever event was the most severe.
At 26 weeks, the group with the greatest proportion of patients who experienced disease progression was the placebo group (n = 35; 39%), followed by the 30 mg BMS-986278 group (n = 24; 29%) and the 60 mg BMS-986278 group (n = 19; 23%).
In all three groups, researchers commonly reported at least 10% decline in relative percent-predicted FVC as the first disease progression event. This event impacted 17% (n = 14) of patients in each BMS-986278 group and 27% (n = 24) of patients in the placebo group.
Out of the remaining three disease progression events considered in this study, the next most common first event was all-cause hospitalization. This outcome was experienced by 11% (n = 10) of patients receiving placebo, 11% (n = 9) of patients receiving 30 mg BMS-986278 and 6% (n = 5) of patients receiving 60 mg BMS-986278.
In contrast, only two patients (one placebo, one 30 mg BMS-986278) from the total cohort had a first progression event of acute exacerbation. A first event of all-cause mortality did not take place in any group, according to researchers.
Between those in the BMS-986278 groups and those in the placebo group, researchers found that the risk for a progression event was reduced in the 60 mg BMS-986278 group (HR = 0.54; 95% CI, 0.31-0.95) and the 30 mg BMS-986278 group (HR = 0.74; 95% CI, 0.44-1.25) using a Cox proportional hazard model.
“The findings from these post hoc analyses from a phase 2 randomized trial of BMS-986278 were consistent with the primary results of the study,” Johnsen told Healio. “Of note, the analyses reiterated the impact of the 60 mg dose of BMS-986278 on delaying time to disease progression for patients with IPF.”
A future study on BMS-986278 is already planned, Johnsen said.
“Bristol Myers Squibb is currently recruiting for its phase 3 ALOFT program, which will continue to evaluate the efficacy, safety and tolerability of BMS-986278 as a novel treatment for people living with both IPF and progressive pulmonary fibrosis,” she said.