Nerandomilast Slows Lung Function Decline, Reduces Mortality Risk in Autoimmune ILD Subgroup

New data from the FIBRONEER-ILD trial show nerandomilast (Jascayd) reduced forced vital capacity decline and substantially lowered mortality risk in patients with autoimmune disease-related interstitial lung diseases and progressive pulmonary fibrosis, with effects consistent with the overall trial population.

Presented at European Alliance of Associations for Rheumatology (EULAR) 2026 Congress, the subgroup analysis examined 325 of 1176 total trial participants who had autoimmune ILDs, representing 27.6% of the full FIBRONEER-ILD population.¹

"The marked reduction in the risk of death (49% in the overall population and 72% in the patients with autoimmune ILDs with the higher dose) suggests nerandomilast may have an effect on survival beyond that mediated by reducing decline in FVC," wrote investigators, who were led by Toby M. Maher, MD, PhD, Department of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine, University of Southern California.

Nerandomilast efficacy in FIBRONEER-ILD autoimmune ILD subgroup

Patients were randomized 1:1:1 to nerandomilast 9 mg twice daily, nerandomilast 18 mg twice daily, or placebo. Eligibility required either nintedanib use at a stable dose for ≥12 weeks or no nintedanib for ≥8 weeks and the primary endpoint was change from baseline in FVC at week 52.¹

In the autoimmune ILD subgroup, adjusted mean changes in FVC at week 52 were -107.1 mL (SE, 25.0) in the placebo group, -61.2 mL (SE, 23.3) in the nerandomilast 9 mg group (difference, 45.9 mL; 95% CI, -20.8 to 112.6), and -64.9 mL (SE, 23.5) in the nerandomilast 18 mg group (difference, 42.2 mL; 95% CI, -24.9 to 109.3).¹

Mean exposure to trial medication was 15.8 months in the autoimmune ILD subgroup, compared with 15.1 months in the overall trial population. The magnitude of FVC preservation was numerically consistent with treatment effects across the full FIBRONEER-ILD population.¹

Nerandomilast mortality and composite clinical event outcomes

Time-to-event analyses over the full trial period showed meaningful reductions in clinically relevant outcomes in the autoimmune ILD subgroup. Nerandomilast 18 mg twice daily had a nominally significant effect on the composite of acute exacerbation of ILD, hospitalization for a respiratory cause, or death (HR, 0.56; 95% CI, 0.33 to 0.94).¹

The 9 mg dose was associated with a numerical reduction in the same composite (HR, 0.66; 95% CI, 0.40 to 1.10). Both doses demonstrated nominally significant reductions in all-cause mortality HR, 0.40 (95% CI, 0.17 to 0.94) for the 9 mg twice-daily dose and HR 0.28 (95% CI, 0.11 to 0.69) for the 18 mg twice-daily dose.¹

The majority of deaths in the autoimmune ILD subgroup had a respiratory cause, either pneumonia or ILD progression. The mortality reduction was numerically larger in the autoimmune ILD subgroup than in the overall trial population, suggesting this population may derive particular benefit.¹

The FIBRONEER-ILD findings in the autoimmune ILD subgroup are further contextualized by a systematic review and meta-analysis also presented at EULAR 2026, which pooled 31 studies involving 2638 patients with RMD-ILD and found antifibrotic agents significantly attenuated annual FVC decline versus placebo (MD 65.87 mL; 95% CI, 40.07 to 91.67).²

That analysis found nintedanib and pirfenidone carried a higher burden of gastrointestinal adverse events and significantly elevated discontinuation rates versus placebo. Nerandomilast, by contrast, showed no significant increase in adverse events or discontinuation rates in available data, and was the only agent to demonstrate a statistically significant pooled reduction in all-cause mortality (RR 0.22; 95% CI 0.12–0.40), though the authors noted this finding derives from a single phase 3 trial and should be interpreted accordingly.²

References

1. Hoffmann-Vold AM, Assassi S, Cottin V, et al. Efficacy of nerandomilast in patients with autoimmune interstitial lung diseases and progressive pulmonary fibrosis in the FIBRONEER-ILD trial. Presented at: EULAR 2026; June 2026.

2. Duarte AC, Rei R, Donato H, Alfaro T, Santos MJ. Antifibrotics in interstitial lung disease related to rheumatic and musculoskeletal diseases: a systematic review and meta-analysis. Presented at: EULAR 2026; June 2026.