Nerandomilast Approval: A New Era for Progressive Pulmonary Fibrosis Treatment

Nerandomilast received FDA approval for progressive pulmonary fibrosis, creating an immediately actionable oral antifibrotic for adults with progressive lung fibrosis and expanding targeted pharmacologic options for a condition with limited therapies. This authorization matters because many patients continue to progress despite current care, and the approval introduces a new mechanism to address fibrosis across interstitial lung disease (ILD) diagnoses.

Clinically, the approval alters treatment selection by introducing an oral preferential phosphodiesterase 4B (PDE4B) inhibitor that can be considered when progressive decline occurs despite existing therapies. PDE4B inhibition combines immunomodulatory and antifibrotic effects, placing nerandomilast mechanistically apart from tyrosine kinase inhibitors and the antifibrotic profiles of nintedanib or pirfenidone. Because background antifibrotic use was a stratification factor in the pivotal program, concurrent or prior use of nintedanib or pirfenidone will inform prescribing patterns and discussions about sequencing or combination. Patients with progressive pulmonary fibrosis across ILD subtypes—particularly those with continued FVC decline on current therapy—are most likely to be considered for the new agent.

FIBRONEER-ILD trial was the pivotal phase 3 randomized, placebo-controlled study enrolling adults with progressive pulmonary fibrosis across ILD diagnoses and stratifying participants by background antifibrotic therapy. The primary endpoint was absolute change from baseline in forced vital capacity (FVC) at week 52; the trial reported adjusted mean declines of approximately −86 mL and −69 mL for the higher and lower tested doses versus −152 mL for placebo, reflecting statistically and clinically meaningful reductions in FVC loss.

Safety data showed similar overall adverse-event rates and tolerability for nerandomilast versus placebo, supporting feasibility in outpatient settings. The profile did not reveal new safety signals compared with existing antifibrotics, though expected gastrointestinal effects and center-specific monitoring pathways warrant routine counseling and follow-up.