Examining Nerandomilast Efficacy in Idiopathic Pulmonary Fibrosis: Insights from CHEST 2025

Nerandomilast (Jascayd) slowed forced vital capacity (FVC) decline over 52 weeks in the FIBRONEER‑IPF Phase 3 trial US subgroup presented at CHEST 2025, a finding that supported recent regulatory approval.The CHEST presentation highlighted both a lung‑function benefit and a lower rate of severe respiratory events in the US cohort.

Relative to existing antifibrotics, nerandomilast delivered a comparable, clinically meaningful reduction in FVC decline while showing a distinct tolerability profile — a practical consideration when selecting therapy. The US subgroup data are particularly relevant for domestic uptake because regulators and payers often weigh local population evidence when assessing benefit, access, and reimbursement.

At week 52, the CHEST 2025 report on MedCentral documented a smaller mean FVC decline in the US subgroup: placebo −257.9 mL versus nerandomilast −152.7 mL (9 mg) and −126.2 mL (18 mg), indicating a preserved FVC trajectory with treatment; although the US placebo decline was steeper than the global placebo, the treatment‑effect magnitude aligned with the overall trial.

The report also described fewer combined acute exacerbations, respiratory hospitalizations, or deaths with nerandomilast versus placebo (25.7% vs 35.7% for 9 mg; 19.6% vs 35.7% for 18 mg), with hazard ratios trending below 1.00 for the higher dose. These CHEST subgroup data were cited during FDA deliberations and informed the agency’s approval decision.

Safety reporting in the US subgroup showed fewer serious adverse events with nerandomilast than with placebo at both 9‑mg and 18‑mg doses. Diarrhea was the most common nonserious adverse event and accounted for most tolerability‑related discontinuations, but overall discontinuation rates were lower with nerandomilast than with placebo — a pattern consistent with manageable adverse events and routine clinic monitoring for most patients.

Key Takeaways:

• Nerandomilast offers a clinically relevant slowing of FVC decline at 52 weeks and lower rates of hospitalization and acute exacerbation in the US subgroup, providing a new oral option after more than a decade without approvals.
• Adults with idiopathic pulmonary fibrosis (IPF), particularly patients intolerant of or inadequately served by current antifibrotics, are most likely to benefit; formulary placement and access decisions will likely reflect the US subgroup data.
• Expect expedited formulary reviews, guideline panel consideration, and institution‑level decisions on monitoring and sequencing with nintedanib or pirfenidone as clinicians and payers integrate the new approval into practice.