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. Announced on December 19, 2025, this decision marks nerandomilast as the first preferential phosphodiesterase 4B (PDE4B) inhibitor with both immunomodulatory and antifibrotic effects approved for this indication. The approval was based on findings from the phase 3 FIBRONEERTM-ILD clinical trial, noted for being the largest clinical trial program focused on PPF to date.
“Progressive pulmonary fibrosis is often associated with underlying interstitial lung disease (ILD) diagnoses, including autoimmune ILDs caused by conditions such as rheumatoid arthritis or systemic sclerosis, as well as hypersensitivity pneumonitis,” stated Dr. Shervin Assassi, Director of Rheumatology at McGovern Medical School, UTHealth Houston. He emphasized that these underlying conditions frequently lead to lung complications that can severely impair lung function, underscoring the need for new treatments like nerandomilast to mitigate the decline in lung function observed in patients.
Nerandomilast was previously approved by the FDA on September 10, 2025, for idiopathic pulmonary fibrosis (IPF) in adult patients. Its efficacy in PPF was evaluated in the FIBRONEERTM-ILD trial, which primarily measured the absolute change from baseline in Forced Vital Capacity (FVC), a standard indicator of lung function, at week 52. Results indicated that nerandomilast significantly reduced the decline in FVC compared to a placebo group. Specifically, the adjusted mean decline in FVC for patients receiving nerandomilast at doses of 18 mg and 9 mg was -86 mL and -69 mL, respectively, compared to -152 mL in the placebo group. The treatment differences were 65 mL (95% CI, 30-101) and 83 mL (95% CI, 48-118).
Clinical Findings and Implications
The trial also assessed a key secondary composite endpoint, which included the time to first occurrence of acute ILD exacerbation, respiratory-related hospitalization, or death over a period of up to 109 weeks. While no statistically significant treatment differences were observed in this endpoint, exploratory analyses suggested that nerandomilast 18 mg was associated with a nominally significant reduction in acute ILD exacerbations (HR, 0.60; 95% CI, 0.38-0.94) compared to placebo. Additionally, there was a numerical reduction in hospitalization risks associated with respiratory issues (HR, 0.82; 95% CI, 0.61-1.11).
In terms of overall survival, analysis at the end of the trial indicated a trend favoring nerandomilast, with similar hazard ratios 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. These results, while promising, were not prespecified for multiplicity control.
The safety profile of nerandomilast was consistent with findings from previous studies involving patients with idiopathic pulmonary fibrosis. Diarrhea was the most common adverse reaction, reported in 49%, 50%, and 37% of patients receiving nerandomilast 18 mg, 9 mg, or placebo, respectively, when used alongside background nintedanib. Among patients not receiving nintedanib, the incidence of diarrhea was lower, occurring in 27%, 16%, and 16% of those treated with nerandomilast 18 mg, 9 mg, and placebo, respectively. Notably, diarrhea led to treatment discontinuation in 4% of patients on nerandomilast 18 mg with background therapy, compared to 1% in the placebo group.
Scott Staszak, President and CEO of the Pulmonary Fibrosis Foundation, expressed optimism over the approval, stating, “People living with progressive pulmonary fibrosis often carry a heavy burden that others don’t always see. A progressive 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.”
The approval of nerandomilast represents a significant advancement in the treatment landscape for patients suffering from progressive pulmonary fibrosis, offering hope for improved management of this challenging condition.
