FDA Approves Nerandomilast, First New IPF Treatment in More Than a Decade

Nerandomilast shows significant efficacy in slowing lung function decline

The FDA has approved nerandomilast 9 mg and 18 mg tablets, to be marketed as Jascayd (Boehringer Ingelheim), for the treatment of adults with idiopathic pulmonary fibrosis (IPF), marking the first new approval for the disease in more than 10 years. The oral, preferential phosphodiesterase 4B (PDE4B) inhibitor demonstrated significant efficacy in reducing forced vital capacity (FVC) decline compared with placebo in phase 3 trials.¹

Clinical Trial Evidence

The approval was supported by data from the randomized, double-blind, placebo-controlled FIBRONEER-IPF trial (NCT05321069)² and Trial 2 (NCT04419506).³ In FIBRONEER-IPF, 1177 patients were randomized 1:1:1 to receive nerandomilast at 9 mg twice daily, nerandomilast at 18 mg twice daily, or a placebo twice daily until the last patient received treatment for 52 weeks. The blinded trial duration was up to 91 weeks, and the end of trial duration was up to 109 weeks.²

The primary endpoint was absolute change from baseline in FVC in milliliters at 52 weeks. Participants receiving nerandomilast experienced significantly less decline in absolute change from baseline in FVC than those who received placebo. In the nerandomilast cohorts, the adjusted mean decline in FVC was –106 mL in the 18-mg group and –122 mL in the 9-mg group. In the placebo group, the adjusted mean decline was –170 mL.²

The drug was well-tolerated, with participants discontinuing due to adverse events at a 14.0% rate in the 18 mg group, 11.7% in the 9 mg, and 10.7% in the placebo arm.²

"After several challenges in the scientific community to bring forward new clinical data, IPF and PPF continue to take a devastating toll on patients," FIBRONEER-IPF investigator Toby Maher, MD, PhD, professor of Clinical Medicine at USC's Keck School of Medicine, said in a statement.³ "Having 2 phase III trials meet the primary endpoint is a major breakthrough for the scientific community, highlighting nerandomilast's potential to have a meaningful impact on patients' unmet needs, being studied as mono therapy or in combination with current treatments."³

Supporting Phase 2 Data

The FDA also reviewed data from Trial 2, a phase 2 study including 147 participants with IPF with or without previous antifibrotic treatments (nintedanib or pirfenidone) randomized 2:1 to receive either nerandomilast at 18 mg twice daily or a twice-daily placebo for 12 weeks. Trial 2 participants taking nerandomilast experienced a 91 mL decline in FVC at 12 weeks (95% CI, 44-138).⁴

Pooled data from FIBRONEER-IPF and FIBRONEER-ILD (NCT05321082) presented at the European Respiratory Society conference demonstrated a nominally significant association for improved survival. In the 18-mg nerandomilast group, there was a 59% reduced risk of death among participants who did not receive background therapy (HR, 0.41; 95% CI, 0.24-0.70).⁵

Safety, Dosing, and MOA

The most common adverse reactions (occurring at a rate of 5% or more) associated with nerandomilast were diarrhea, COVID-19, upper respiratory tract infection, depression, decreased weight, decreased appetite, nausea, fatigue, headache, vomiting, back pain, and dizziness. Diarrhea was most commonly associated with treatment discontinuation.⁴

The recommended dosage for nerandomilast is 18 mg orally twice a day, approximately 12 hours apart. Except in adults also taking pirfenidone, dosage may be reduced for intolerability to 9 mg twice daily.⁴

PDE4 inhibition permits increased intracellular cyclic adenosine monophosphate levels and reduces the expression of profibrotic growth factors and inflammatory cytokines that are overexpressed in IPF.^2,3

IPF is a chronic, rare, serious, and progressive disease with no cure and limited treatments. It affects the alveoli, causing the walls to become thick and stiff. Fibrosis develops over time, impeding air flow. The most common symptoms are shortness of breath and cough. IPF progression varies, and scarring may happen slowly or quickly. Many people with IPF also experience acute exacerbations, in which symptoms suddenly intensify. IPF is diagnosed most often in people 60 to 70 years of age.^2,3

References

1. FDA approves drug to treat idiopathic pulmonary fibrosis. FDA. News release. October 7, 2025. Accessed October 8, 2025. https://content.govdelivery.com/accounts/USFDA/bulletins/3f61959
2. Halsey G. IPF Update: FIBRONEER-IPF Study of Nerandomilast Meets Primary End Point. Primary Care. September 13, 2024. Accessed October 8, 2025. https://www.patientcareonline.com/view/ipf-update-fibroneer-ipf-study-of-nerandomilast-meets-primary-end-point
3. Global phase III trials demonstrate that nerandomilast slowed lung function decline in IPF and PPF, with similar discontinuation rates to placebo. Boehringer Ingelheim. May 19, 2025. Accessed October 8, 2025. https://www.boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/phase-3-trials-nerandomilast-slowed-lung-function-decline-ipf-and-ppf.
4. Jascayd. Prescribing information. Boehringer Ingelheim; 2025. Accessed October 7, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218764s000lbl.pdf
5. Pooled data presented at ERS: nerandomilast monotherapy linked to nominally significant reduction in risk of death in IPF and PPF. Boehringer Ingelheim. News release. September 29, 2025. Accessed October 8, 2025. https://www.boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/nerandomilast-monotherapy-ipf-ppf-death-reduction