The U.S. Food and Drug Administration (FDA) has approved Boehringer Ingelheim’s nerandomilast (Jascayd) tablets for the treatment of progressive pulmonary fibrosis (PPF) in adults. This decision, announced on December 19, 2025, makes nerandomilast the first and only preferential phosphodiesterase 4B (PDE4B) inhibitor with both immunomodulatory and antifibrotic effects sanctioned for this condition. The approval is based on results from the phase 3 FIBRONEERTM-ILD clinical trial, the most extensive clinical trial program conducted for PPF to date.
“Progressive pulmonary fibrosis is linked to underlying clinical interstitial lung disease (ILD) diagnoses, including autoimmune ILDs,” stated Dr. Shervin Assassi, Director of Rheumatology at McGovern Medical School, UTHealth Houston. He highlighted that conditions such as rheumatoid arthritis and systemic sclerosis can contribute to lung scarring, which often goes unnoticed but significantly affects lung function and patients’ quality of life. The need for new treatments to mitigate these declines is critical, as evidenced by the observed benefits of nerandomilast.
Nerandomilast, an oral treatment also approved for idiopathic pulmonary fibrosis (IPF) on September 10, 2025, was specifically evaluated for its efficacy in PPF during the FIBRONEERTM-ILD trial. The primary endpoint assessed the absolute change in Forced Vital Capacity (FVC), a measure of lung function, at week 52. Results indicated that patients receiving nerandomilast experienced a significantly smaller reduction in FVC decline compared to those on placebo. The adjusted mean declines in FVC for patients taking nerandomilast were -86 mL for the 18 mg dose and -69 mL for the 9 mg dose, while the placebo group saw a decline of -152 mL. The treatment differences were 65 mL (95% CI, 30-101) and 83 mL (95% CI, 48-118) respectively.
In addition to the primary endpoint, the trial also measured key secondary outcomes, including the time to the first occurrence of acute ILD exacerbation, hospitalization for respiratory causes, or death over the blinded duration of the trial, which lasted up to 109 weeks. No statistically significant differences in hazard ratios (HR) were found between the nerandomilast groups and placebo for these secondary outcomes. The HRs for the 18 mg and 9 mg groups compared to placebo were 0.77 (95% CI, 0.59-1.01) and 0.88 (95% CI, 0.68-1.14), respectively.
Exploratory analyses suggested that the 18 mg dose of nerandomilast could reduce the risk of acute ILD exacerbations during the trial compared to placebo (HR, 0.60; 95% CI, 0.38-0.94). The data also indicated a numerical reduction in hospitalization for respiratory causes (HR, 0.82; 95% CI, 0.61-1.11), though these results were not statistically significant. Furthermore, a prespecified analysis of overall survival at the end of the trial showed a promising trend favoring nerandomilast, with HRs for all-cause mortality at 0.51 (95% CI, 0.34-0.78) for both the 18 mg and 9 mg groups compared to placebo.
The safety profile of nerandomilast in patients with PPF was consistent with earlier findings in patients with IPF. Diarrhea was the most frequently reported adverse reaction, occurring in 49% of patients on the 18 mg dose and 50% on the 9 mg dose, compared to 37% in the placebo group when taken alongside background therapy of nintedanib. Among patients not receiving nintedanib, diarrhea rates were lower, at 27% for the 18 mg group and 16% for both the 9 mg group and placebo. Treatment discontinuation due to diarrhea was most common in patients on the higher dose of nerandomilast.
Scott Staszak, President and CEO of the Pulmonary Fibrosis Foundation, remarked, “People living with progressive pulmonary fibrosis often carry a heavy burden that others don’t always see. A progressive disease condition like PPF can worsen lung function quickly, and patients have been eagerly awaiting additional treatment options. The FDA approval of nerandomilast for PPF is a welcomed milestone for the community.”
This approval marks a significant advancement in the treatment landscape for progressive pulmonary fibrosis, offering hope to patients and healthcare providers alike. With the growing recognition of the complexities associated with PPF, the introduction of new therapies like nerandomilast is crucial in addressing unmet medical needs.
