Nerandomilast Shows Promise in Slowing Lung Function Decline in Pulmonary Fibrosis

A new systematic review and meta-analysis suggests that nerandomilast (Jascayd; Boehringer Ingelheim), an oral therapy for pulmonary fibrosis (PF), can help slow disease progression without adding significant safety risks. The findings offer hope for improving outcomes in a condition where treatment options remain limited and disease progression is often relentless.¹

While previously approved antifibrotic therapies, such as nintedanib (Ofev; Boehringer Ingelheim) and pirfenidone (Esbriet; Genentech), can slow disease progression, many patients continue to experience decline or are unable to tolerate treatment due to side effects. Nerandomilast, a selective phosphodiesterase-4B (PDE4B) inhibitor, received the greenlight from the FDA at the tail end of 2025.² The drug works by modulating cyclic AMP signaling pathways, which are involved in inflammation and fibrotic processes, ultimately aiming to reduce fibroblast activity and the buildup of scar tissue in the lungs.

Nerandomilast represents one of the first oral antifibrotic agents in years to demonstrate meaningful effects on lung function decline in both idiopathic PF and progressive PF populations. The drug also has potential for use in combination with existing therapies, such as nintedanib, to further enhance treatment outcomes.

Prior to its approval, investigators conducted a meta-analysis of randomized controlled trials comparing nerandomilast with placebo in patients with pulmonary fibrosis, publishing their findings in March 2026 in The Clinical Respiratory Journal. The analysis included 4 trials comprising of 2515 participants across multiple countries, making it one of the most comprehensive evaluations of the therapy to date.

The primary outcome of interest was the change in forced vital capacity (FVC), a key measure of lung function and disease progression. According to results, nerandomilast significantly slowed the decline in FVC compared with placebo over a 52-week period. Patients receiving the drug experienced an average improvement of approximately 69 mL (95% CI, 52.1-86.29) in FVC decline relative to controls, a statistically significant difference with low variability across studies.

This benefit was observed across different types of pulmonary fibrosis, including both idiopathic and nonidiopathic forms, suggesting that nerandomilast may have broad applicability in this patient population.

However, when researchers evaluated diffusing capacity for carbon monoxide (DLCO), another measure of lung function reflecting gas exchange, they found no significant improvement with nerandomilast (MD, 0.84; 95% CI, −0.56 to 2.24). The researchers explained this may be due to the complexity of DLCO as a composite measure or the relatively short duration of some included studies.

Beyond lung function, the study also explored clinical outcomes such as mortality. Pooled results showed that patients treated with nerandomilast had a lower risk of all-cause mortality compared with those receiving placebo, with a relative risk reduction of approximately 32% (RR, 0.68; 95% CI, 0.52-0.88), suggesting a potential survival benefit.

However, researchers cautioned that individual trials were not specifically powered to assess mortality, and event rates were relatively low. As a result, while the findings are encouraging, they should be interpreted with caution and confirmed in future studies.

The findings also pointed to a favorable tolerability profile associated with the treatment, which could be particularly important for patients who are unable to tolerate current antifibrotic therapies. Encouragingly, the meta-analysis found no significant difference in the overall risk of side effects between nerandomilast and placebo (RR, 1.00; 95% CI, 0.98-1.02). Rates of serious side effects (RR, 0.93; 95% CI, 0.76-1.14) and treatment discontinuation were also comparable between groups.

Despite the promising results, the researchers emphasized several limitations, including variability in study populations, differences in trial design, and the relatively short duration of some studies. They highlighted the need for larger, long-term randomized trials to confirm the durability of benefits and better understand the drug’s impact on survival and quality of life.

References:

1. Shahzad H, Afzaal U, Saleem F, et al. Safety and efficacy or nerandomilast in patients with pulmonary fibrosis: a systematic review and meta-analysis of randomized controlled trials. Clin Respir J. Published online March 11, 2026. doi:10.1111/crj.70181

2. FDA approves drug to treat chronic, progressive lung disease. FDA news release. Last updated December 19, 2025. Accessed March 19, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-treat-chronic-progressive-lung-disease