Nerandomilast is both effective and well-tolerated, representing a “major step forward for the treatment of progressive pulmonary fibrosis (PPF),” with its effect on clinical outcomes sustained over 76 weeks, according to findings from the FIBRONEER-ILD trial presented in a poster at the European Respiratory Society Congress 2025.1
PPF is a condition with high mortality, and new treatments are needed as the only approved therapy, nintedanib, has gastrointestinal side effects that often lead to discontinuation. Nerandomilast is a promising oral medication that acts as a preferential inhibitor of phosphodiesterase 4B, giving it both antifibrotic and immunomodulatory properties.
The FIBRONEER-ILD study was a randomized, placebo-controlled trial involving adult patients (placebo, n = 392; nerandomilast, n = 393) with an interstitial lung disease (ILD) other than IPF who showed evidence of disease progression. Participants were randomized in a 1:1:1 ratio to receive either nerandomilast 9 mg twice daily, nerandomilast 18 mg twice daily, or a placebo.
The study design stratified patients based on their use of nintedanib and their fibrotic pattern on high-resolution computed tomography scans. The primary endpoint was the absolute change in forced vital capacity (FVC) from baseline at week 52. The trial continued beyond this point, with prespecified analyses evaluating outcomes over 76 weeks and time-to-event endpoints up to a final database lock.
The trial concluded that the effect of both nerandomilast doses reduces FVC significantly more than placebo. This positive impact on lung function was further supported by a reduction in clinical events that are meaningful to patients, as measured by the key secondary endpoint.
Crucially, the study found a nominally significant reduction in the risk of death for patients taking nerandomilast at both the first and final database locks. In terms of safety, the proportion of patients who had to stop treatment due to adverse events was similar between the nerandomilast (9 mg vs 19 mg) and placebo groups (background nintedanib, 96.5% vs 96.5% vs 95.3%; no background nintedanib, 95.0% vs 94.5% vs 93.2%). These findings suggest nerandomilast is both effective and well-tolerated, representing a “major step forward for the treatment of PPF.”
Another poster assessing the FIBRONEER study featured a pooled analysis of the trials evaluating nerandomilast, a novel phosphodiesterase 4B inhibitor, as a treatment for Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), 2 fatal lung diseases with limited therapeutic options.2 Current standard therapies, nintedanib and pirfenidone, can slow lung function decline but are often poorly tolerated due to adverse events, leading to high discontinuation rates. Nerandomilast, administered orally at doses of 9 mg or 18 mg twice daily, has both antifibrotic and immunomodulatory properties, offering a potentially safer alternative.
In both the FIBRONEER-IPF and FIBRONEER-ILD trials, nerandomilast met the primary endpoint of reducing decline in forced vital capacity (FVC) at 52 weeks compared with placebo. Data from the trials were pooled and analyzed for longer-term outcomes up to 76 weeks. In patients not receiving background antifibrotic therapy, nerandomilast significantly reduced the risk of key clinical events and mortality with both tested doses. Among patients already on nintedanib, the higher 18 mg dose of nerandomilast also showed a significant reduction in mortality risk. Importantly, nerandomilast demonstrated a favorable safety profile, with adverse event–related discontinuation rates similar to placebo, distinguishing it from currently approved therapies. However, benefits were not as prominent in patients taking nerandomilast with ninitanib and perfenidone compared with those taking nerandomilast alone.
These findings suggest that nerandomilast is effective in slowing disease progression while maintaining tolerability. Its efficacy as both a monotherapy and in combination with nintedanib positions it as a promising treatment option for IPF and PPF, potentially expanding therapeutic choices for patients facing these life-limiting conditions.
References
- Wijsenbeek MS, Assassi S, Azuma A, et al. Late breaking abstract – effect of nerandomilast on clinical outcomes in patients with progressive pulmonary fibrosis (PPF): results from the final database lock of the FIBRONEER-ILD trial. Presented at ERS Congress 2025; September 27-October 1, 2025; Amsterdam, Netherlands. Poster 1147.
- Oldham JM, Assassi S, Azuma A, et al. Late breaking abstract – safety and tolerability of nerandomilast in patients with pulmonary fibrosis: pooled data from the FIBRONEER-IPF and FIBRONEER-ILD trials. Presented at ERS Congress 2025; September 27-October 1, 2025; Amsterdam, Netherlands. Poster 2977.