GLASGOW, Scotland — The antifibrotic medication nerandomilast works in people with rheumatic disease and progressive pulmonary fibrosis (PPF) just as well as it does in the general population of patients with interstitial lung disease (ILD), new data from the FIBRONEER-ILD study have shown.

Nerandomilast is a phosphodiesterase 4B inhibitor that was approved by the FDA in 2025 for adults with idiopathic pulmonary fibrosis (IPF) or PPF and is undergoing evaluation by the European Medicines Agency and the UK’s Medicines Healthcare products Regulatory Agency. 

In a subgroup analysis involving 325 patients with autoimmune disease-related PPF, the primary endpoint of absolute change from baseline to week 52 in forced vital capacity (FVC) was a mean of -61.2 mL and -64.9 mL for the 9 mg and 18 mg twice daily oral doses of nerandomilast that were used, respectively, vs -107.1 mL for placebo. The relative reductions for the two doses of nerandomilast vs placebo were a respective 43% and 39%.

“The efficacy of nerandomilast on slowing decline in FVC was consistent with that observed in the overall trial population,” study investigator Anna-Maria Hoffmann-Vold, MD, PhD, said at the British Society for Rheumatology (BSR) 2026 Annual Meeting. 

The mean FVC changes in the overall population, which consisted of 1176 participants, had been a respective -84.6 mL, -98.6 mL, and -165.8 mL, with relative reductions of 49% and 41% for the nerandomilast 9 mg and 18 mg twice daily doses vs placebo. 

Reduced Mortality Signal  

“Very excitingly, even though it was not met in the entire patient population, the key secondary endpoint was met in our autoimmune ILD patients, so less hospitalizations, less acute exacerbations, and less death,” Hoffmann-Vold, professor of rheumatology and consultant rheumatologist at Oslo University Hospital, Norway, told Medscape Medical News. 

Treatment with the 18 mg twice daily dose produced a significant 44% reduction in the composite endpoint of ILD exacerbation, hospitalization for a respiratory cause, or death at 1 year. There had been a nonsignificant reduction of 34% in this composite endpoint with the 9 mg twice daily dose.

All of the individual components of this endpoint were reduced significantly with the 18 mg twice daily dose. Although reduced with the 9 mg twice daily dose, results were statistically significant only for the reduction in the risk for death, at 60%. The risk reduction for death was 72% with the higher dose.

“No study [in ILD] has ever shown reduction of deaths within 52 weeks; that wasn't expected,” Hoffmann-Vold said, who qualified that this was a reduction in deaths due to ILD. 

Study Details 

FIBRONEER-ILD was a multicenter, multinational, phase 3 randomized control trial that investigated the safety and efficacy of nerandomilast in adults with a confirmed diagnosis of ILD other than IPF.

Participants were required to have ILD progression within the previous 24 months, at least 10% or more of their lungs affected by fibrosis as seen on high-resolution CT, a diffusing capacity of the lungs for carbon monoxide value of 25% predicted or higher, and a predicted FVC of 45% or more. 

Participants already taking nintedanib could be included, so long as they had not taken the drug within the past 8 weeks or if the dose taken had remained stable for a minimum of 12 weeks. In all, just over a third (34.2%) of the participants with autoimmune disease-related ILD were taking nintedanib. 

Participants were not permitted to take immunosuppressants or glucocorticoids at enrollment, but these could be initiated after 6 months if needed to manage worsening systemic disease. Just over half (55.1%) of the participants with autoimmune disease-related ILD were treated with immunosuppressants.

Hoffmann-Vold said that the most common autoimmune diseases among patients in the subanalysis were rheumatoid arthritis (n = 118), systemic sclerosis (n = 75), and mixed connective tissue disease (n = 47).

The subgroup study findings have been accepted for publication in Annals of the Rheumatic Diseases, according to Hoffmann-Vold.

Safety Findings 

Serious adverse events and adverse events leading to treatment discontinuation were similar with nerandomilast and placebo and also similar regardless of the use of nintedanib. 

However, there were some differences in the types of adverse events experienced according to whether nintedanib was taken. For instance, the most frequent side effect was diarrhea, occurring in 19.2% of patients taking the 9 mg twice daily dose and 22.9% of those taking the 18 mg twice daily dose, and 19.7% of those given placebo but who had not been taking nintedanib. In those who had received concomitant nintedanib treatment, diarrhea rates were higher, at a respective 46.2%, 44.2%, and 34.5%. Joint pain appeared more common when nintedanib was used (15.4%, 14.0%, and 6.9%) than when it was not (6.8%, 8.6%, and 2.8%). Nausea also occurred more often when nintedanib was used vs not (12.8%, 23.3%, and 8.6% vs 1.4%, 8.6%, and 0%).

Key Takeaways 

Voon Ong, MBBS, PhD, a consultant rheumatologist at the Royal Free Hospital and senior clinical lecturer and professor of experimental rheumatology at University College London, England, commented to Medscape Medical News that “for a drug in ILD to have impact on mortality, that is uniquely very interesting.”

ILD is an important complication, Ong observed: “Clearly, it’s associated with high mortality and currently we need to do better.” Antifibrotics have been shown to slow the decline of lung function in ILD, he said, but they had not really had an impact on mortality in connective tissue diseases, certainly not in scleroderma, which is his main specialist interest. 

“The only complication in which drugs have shown to have an impact on mortality is in the area of pulmonary hypertension,” he qualified. “To have a drug that has an impact on mortality, it’s of huge interest and a benefit for patients with ILD.”

Respiratory medicine consultant Nazia Chaudhuri, MBChB, PhD, who is a senior clinical lecturer at the University of Ulster, UK, told Medscape Medical News: “From an ILD perspective, getting a mortality signal is very, very difficult because you need trials to run for many years with thousands and thousands of patients.”

However, Chaudhuri added: “Even though this is a secondary endpoint, and it’s not powered [to make the comparison], the fact that they saw a mortality signal is really compelling from a clinician’s perspective and a patient perspective. It is fantastic news to hear that not only do the drugs slow decline, but they will help patients live longer.”

Boehringer Ingelheim funded the study. 

Hoffmann-Vold has received research support from Boehringer Ingelheim and Janssen. She has also acted as a speaker or consultant to AbbVie, Avalyn, Boehringer Ingelheim, Bristol Myers Squibb, Calluna Pharma, Genentech, Janssen, Medscape, Merck, Novartis, Pliant Therapeutics, Roche, and Werfen. 

Ong has acted an investigator for and consultant to Boehringer Ingelheim. 

Chaudhuri was an investigator for the INBUILD trial of nintedanib in patients with PPF, which was funded by Boehringer Ingelheim. 

Sara Freeman is a medical journalist based in London, UK.