The U.S. Food and Drug Administration (FDA) has approved Boehringer Ingelheim’s nerandomilast (marketed as Jascayd) tablets for the treatment of progressive pulmonary fibrosis (PPF) in adults. This landmark decision, announced on December 19, 2025, marks nerandomilast as the first and only preferential phosphodiesterase 4B (PDE4B) inhibitor with both immunomodulatory and antifibrotic effects approved for this condition. The approval was based on comprehensive results from the phase 3 FIBRONEERTM-ILD clinical trial, which is the largest clinical trial program conducted for PPF to date.
Dr. Shervin Assassi, Director of Rheumatology at McGovern Medical School, UTHealth Houston, emphasized the significance of this approval. He noted that progressive pulmonary fibrosis is often associated with interstitial lung disease (ILD) diagnoses, including autoimmune conditions like rheumatoid arthritis and systemic sclerosis, as well as other illnesses such as hypersensitivity pneumonitis. “These underlying conditions often lead to the lungs being overlooked, yet lung scarring may lead to debilitating and irreversible impact on lung function,” Dr. Assassi remarked. He stressed the urgent need for new treatment options like nerandomilast to help slow the decline in lung function.
Nerandomilast is administered orally and was previously approved by the FDA as a treatment option for idiopathic pulmonary fibrosis (IPF) on September 10, 2025. Its effectiveness in treating PPF was evaluated in the FIBRONEERTM-ILD trial. The primary endpoint of the trial focused on the absolute change in Forced Vital Capacity (FVC), a critical measure of lung function, after 52 weeks. Results indicated that patients taking nerandomilast experienced a significantly smaller decline in FVC compared to those receiving a placebo. 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. This translates to a treatment difference of 65 mL (95% CI, 30-101) and 83 mL (95% CI, 48-118).
The trial also explored key secondary endpoints, including the time to the first occurrence of acute ILD exacerbation, hospitalization for respiratory issues, or death. Although the results did not show statistically significant differences in hazard ratios (HR) for these outcomes, exploratory analyses suggested that nerandomilast 18 mg demonstrated a nominally significant reduction in acute ILD exacerbations compared to placebo (HR, 0.60; 95% CI, 0.38-0.94). Additionally, a numerical reduction in hospitalization risk for respiratory causes was observed in this group (HR, 0.82; 95% CI, 0.61-1.11).
Survival rates were also analyzed, with the data showing a trend favoring nerandomilast for all-cause mortality at the end of the trial, which lasted up to 114 weeks. The HRs for mortality for the nerandomilast 18 mg and 9 mg groups compared to placebo were both 0.51 (95% CI, 0.34-0.78).
In terms of tolerability, nerandomilast was generally well-received by patients. The most common adverse reaction reported was diarrhea, which occurred in 49%, 50%, and 37% of patients treated with nerandomilast 18 mg, nerandomilast 9 mg, and placebo, respectively, among those receiving background treatment with nintedanib. In patients not on nintedanib, the incidence of diarrhea was notably lower, occurring in 27%, 16%, and 16% of patients on nerandomilast 18 mg, nerandomilast 9 mg, and placebo, respectively.
Scott Staszak, President and CEO of the Pulmonary Fibrosis Foundation, acknowledged the approval as a significant milestone for the PPF community. “People living with progressive pulmonary fibrosis often carry a heavy burden that others don’t always see,” he stated. “A progressive disease like PPF can worsen lung function quickly, and patients have been eagerly awaiting additional treatment options.”
The FDA’s approval of nerandomilast is expected to provide a new avenue for treatment in a patient population that has long faced limited options. With the potential to improve lung function and overall quality of life, this development is a hopeful advance in the fight against progressive pulmonary fibrosis.
