FDA approves nerandomilast for idiopathic pulmonary fibrosis

The Food and Drug Administration approved nerandomilast, marketed as Jascayd, on 7 October for the treatment of idiopathic pulmonary fibrosis [s1]. It is the 33rd novel drug the agency has approved in 2025 [s1].

The application record shows the approval was granted under priority review as a Type 1 new molecular entity carrying orphan designation, under new drug application 218764, with an approval status date of 7 October 2025 [s3]. The sponsor is Boehringer Ingelheim Pharmaceuticals [s3], which also funded the trial the approval rests on [s2].

What idiopathic pulmonary fibrosis leaves patients with

IPF is a progressive scarring disease of the lung with no cure. Two antifibrotic medicines, nintedanib and pirfenidone, slow the rate at which lung function declines; neither reverses fibrosis. The endpoint the field has settled on is forced vital capacity — the volume of air a person can forcibly exhale after a full breath — measured as absolute change from baseline over a year.

That is the endpoint the trial supporting this approval used.

The trial

FIBRONEER-IPF was a phase 3, double-blind trial that randomised 1,177 patients with IPF in a 1:1:1 ratio to nerandomilast 18 mg twice daily, nerandomilast 9 mg twice daily, or placebo [s2]. Randomisation was stratified according to whether patients were taking background antifibrotic therapy — nintedanib or pirfenidone — or none [s2]. At enrolment, 77.7 percent were taking one of the two [s2].

The primary endpoint was absolute change from baseline in forced vital capacity, in millilitres, at week 52 [s2].

Adjusted mean changes in FVC at week 52 were −114.7 mL (95% CI −141.8 to −87.5) in the 18 mg group, −138.6 mL (−165.6 to −111.6) in the 9 mg group, and −183.5 mL (−210.9 to −156.1) on placebo [s2]. The adjusted difference between the 18 mg group and placebo was 68.8 mL (30.3 to 107.4; P<0.001), and between the 9 mg group and placebo, 44.9 mL (6.4 to 83.3; P=0.02) [s2].

Every group lost lung function. The drug slowed the loss; it did not stop or reverse it. The conclusion the authors state is exactly that: treatment resulted in a smaller decline in FVC than placebo over 52 weeks [s2].

What the trial did not measure

FIBRONEER-IPF was powered for a lung-function endpoint at one year. It was not designed to demonstrate a survival benefit, and the published results do not report one. Whether a 68.8 mL difference in FVC at 52 weeks translates into longer life or fewer exacerbations is a separate question that a differently designed trial would have to answer.

This is not a criticism unique to nerandomilast — it is how the existing IPF antifibrotics were approved too, and it is why FVC decline has become the field's regulatory currency. It is worth stating plainly because the difference between "slows a spirometry measure" and "helps people live longer" is the difference most readers care about, and only the first has been shown here.

The trial's design also means the result is largely an add-on result. With 77.7 percent of participants on background nintedanib or pirfenidone [s2], the question the trial mostly answered was what nerandomilast adds to existing therapy, not how it performs against it.

The tolerability problem

The most frequent adverse event in the nerandomilast groups was diarrhoea, reported in 41.3 percent of the 18 mg group and 31.1 percent of the 9 mg group, against 16.0 percent on placebo [s2]. Serious adverse events were balanced across groups [s2].

Diarrhoea in 41.3 percent of patients on the higher dose is a substantial burden for a medicine taken indefinitely, particularly in a population already contending with nintedanib, whose own gastrointestinal profile is well known. The 9 mg dose showed a smaller FVC benefit with less diarrhoea [s2], which frames the dosing decision as a genuine trade-off rather than a formality.

Where the mechanism comes from

Nerandomilast, developed as BI 1015550, is an orally administered preferential inhibitor of phosphodiesterase 4B with antifibrotic and immunomodulatory effects [s2]. A phase 2 trial in IPF patients had shown stabilised lung function over 12 weeks [s2].

PDE4 inhibition is not new to respiratory medicine — roflumilast is used in COPD — but preferential targeting of the 4B subtype is the design intended to retain anti-inflammatory activity while limiting the class's gastrointestinal and neuropsychiatric effects. The diarrhoea rates suggest that separation is partial at best.

What this changes

Clinicians treating IPF now have a medicine with a mechanism distinct from the two established antifibrotics. For patients already declining on nintedanib or pirfenidone, the trial provides evidence that adding nerandomilast slows that decline further over a year [s2].

What it does not provide is evidence about years two, three and five, about mortality, or about patients who cannot tolerate an antifibrotic at all. Those are the gaps that post-approval evidence will have to fill.

What to watch

The practical questions now are how the labelled dosing handles the tolerability gradient between 18 mg and 9 mg, whether real-world discontinuation tracks the trial's diarrhoea rates, and whether any longer-term outcome data emerge. The approval covers idiopathic pulmonary fibrosis in adults [s1]; it does not extend to other fibrosing lung diseases.

Sources

• Novel Drug Approvals for 2025 — U.S. Food and Drug Administration, approval dated 7 October 2025
• Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis (FIBRONEER-IPF) — The New England Journal of Medicine, 18 May 2025
• Drugs@FDA application record: NDA 218764 (JASCAYD) — U.S. Food and Drug Administration, approval status date 7 October 2025