FIBRONEER-ON: Nerandomilast's Durable IPF, PPF Safety, With Wim Wuyts, MD, PhD

Interim data from FIBRONEER-ON, the open-label extension of the phase 3 FIBRONEER-IPF and FIBRONEER-ILD trials, show that nerandomilast's favorable safety profile held up with longer-term use, according to Wim A. Wuyts, MD, PhD, professor at KU Leuven and head of the Unit for Interstitial Lung Diseases at University Hospitals Leuven.

Wuyts discussed the late-breaking abstract, presented at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain, held September 5 to 9, in an interview with HCPLive. Nerandomilast, an oral phosphodiesterase 4B (PDE4B) inhibitor, previously slowed decline in forced vital capacity (FVC) versus placebo in both parent trials, with a survival signal also observed in FIBRONEER-ILD, which enrolled patients with progressive pulmonary fibrosis (PPF).1

In FIBRONEER-ON, 1102 patients who received nerandomilast in the parent trials continued the drug, and 541 patients previously on placebo initiated it, with rollover rates exceeding 95% in both groups.2 At baseline of the extension, FVC was 74.7% and 71.4% predicted in the continued and initiated groups, respectively, and 43.1% and 17.2% of patients overall were on background nintedanib or pirfenidone.2 Adverse events led to discontinuation of nerandomilast in 6.9% of patients who continued treatment and 10.2% of those newly initiating it; diarrhea was the most frequent adverse event but led to discontinuation in fewer than 1% of patients overall.2

“I would be really curious to see how that holds on the longer term, and I was highly surprised to see that this was confirmed in the open-label trial,” Wuyts said of the drug's durability.

Wuyts said diarrhea was reported in about 24.8% of newly initiating patients versus 16% of those continuing treatment, and speculated this may partly reflect early-onset side effects that ease over time, alongside possible survivor bias among patients who had already tolerated the drug in the parent trials. He noted only 1.7% of patients in the open-label extension required a dose reduction from 18 mg to 9 mg twice daily, which he took as an indirect sign of the drug's tolerability. He also said investigators appeared to prioritize keeping patients on the highest nerandomilast dose, in some cases adjusting background antifibrotic therapy rather than reducing nerandomilast when side effects arose, though he cautioned this interpretation is speculative.

Looking ahead, Wuyts said he is most interested in longer-term FVC and quality-of-life data from the extension, particularly for patients who initiated nerandomilast without prior exposure in a parent trial, as well as outcomes in the subset of patients with underlying connective tissue disease who required additional immunosuppressive therapy. He said further results are expected to be presented at a future meeting, potentially the American Thoracic Society conference next year.

Wuyts’ disclosures include Roche and Boehringer Ingelheim.

References

1. Richeldi L, Azuma A, Cottin V, et al; FIBRONEER-IPF Trial Investigators. Nerandomilast in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2025;392(22):2193-2202. doi:10.1056/NEJMoa2414108

2. Wuyts W, Assassi S, Azuma A, et al. Safety and tolerability of nerandomilast in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF): data from FIBRONEER-ON. Late-breaking abstract presented at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.