Nerandomilast Tablets (Jascayd)

By William Elliott, MD, FACP, and James Chan, PharmD, PhD

The U.S. Food and Drug Administration has approved nerandomilast for the treatment of idiopathic pulmonary fibrosis (IPF). It is the first preferential inhibitor of phosphodiesterase 4B (PDE4B). Nerandomilast is distributed by Boehringer Ingelheim Pharmaceuticals, Inc. as Jascayd.

Indications

Nerandomilast is indicated for the treatment of IPF in adult patients.¹

Dosage

The recommended dose is 18 mg orally twice daily approximately 12 hours apart with or without food.¹ For patients unable to tolerate this dose, it may be reduced to 9 mg twice daily, except in patients taking concomitant pirfendone.¹ The combination of pirfendone and nerandomilast results in the reduction in the plasma concentration of the latter by approximately 50%.¹ Nerandomilast is a CYP3A4 substrate; the dose should be reduced to 9 mg twice daily when taken concomitantly with a strong CYP3A inhibitor. Use with a moderate or strong CYP3A4 inducer should be avoided. Nerandomilast may be dispersed in non-carbonated, room-temperature water for patients who have difficulty swallowing tablets. Nerandomilast is available as 9 mg and 18 mg tablets.¹

Potential Advantages

The addition of nerandomilast to background antifibrotic therapy (i.e., nintedanib or pirfenidone) slows the decline in forced vital capacity (FVC) over the period of 52 weeks compared to the addition of a placebo.^1,2

Potential Disadvantages

Most common (> 10% vs. placebo) adverse reactions associated with nerandomilast are diarrhea (31% to 42% vs. 17%), COVID-19 (13% to 16% vs. 12%), upper respiratory tract infection (11% to 13% vs. 10%), depression (11% to 12% vs. 10%), and weight decrease (10% to 11% vs. 8%).¹ Diarrhea is most common (50% to 62%) in patients taking concomitant nintedanib, with up to a 13% discontinuation rate.¹ Based on animal studies, nerandomilast may increase the risk for fetal loss.¹

Comments

Nerandomilast preferentially inhibits PDE4, reducing expression of pro-fibrotic growth factors and inflammatory cytokines.¹ Its efficacy in patients with idiopathic pulmonary fibrosis was evaluated in two randomized, double-blind, placebo-controlled trials, FIBRONEER-IPF and Trial 2.^1-3 In both studies, participants had a diagnosis of IPF based on American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) criteria, ≥ 40 years of age with FVC ≥ 45% of predicted and carbon monoxide diffusing capacity (DLCO, corrected for hemoglobin) ≥ 25% of predicted. Participants were required to be naïve of, previously discontinued, or on stable treatment with nintedanib or pirfenidone. FIBRONEER-IPF trial participants were 83% male, mean age of 70 years, 68% white, mean FVC of 78% of predicted normal, and 78% were on stable antifibrotic treatment (nintedanib 46% and pirfenidone 32%). Participants were randomized to nerandomilast 9 mg twice daily (n = 392), 18 mg twice daily (n = 392), or placebo (n = 393). The primary endpoint was the absolute change from baseline in FVC at week 52. The nerandomilast treatment groups showed less decline in absolute change from baseline, -106 mL (18 mg), -122 mL (9 mg), and -170 mL (placebo) with treatment difference compared to placebo of 64 mL (95% confidence interval [CI], 24, 102) and 48 mL (95% CI, 10, 86), respectively. Trial 2, a Phase II study (n = 147) that included participants with or without background antifibrotic treatment, had a reduction in FVC decline of 91 mL at week 12.¹ The key secondary endpoint for FIBRONEER-IPF was time to first occurrence of any components of the composite endpoint over the blinded duration (up to 91 weeks). These include acute IPF exacerbation, hospitalization for respiratory cause, or death. There was no statistically significant treatment difference compared to placebo in the composite endpoint nor in all cause mortality.¹

Clinical Implications

IPF is a rare disease but is one of the more common, progressive fibrosing lung diseases affecting more men than women. It is more common after the age of 50 years.⁴ The disease affects quality of life and about 50% die of the disease within five years of diagnosis. Currently, antifibrotic drugs (nintedanib and pirfenidone) are first-line therapy and have demonstrated slowing in the rate of decline in FVC. Nerandomilast appears to have a modest slowing of FVC decline when added to background antifibrotic therapy. For those not on background therapy, the placebo subtracted differences were numerically less than those reported for nintedanib and pirfenidone alone.^1,5,6 A systematic review and meta-analysis suggest a 30% reduced risk of all-cause mortality with antifibrotic drugs.⁷ Nerandomilast, when used alone or added to antifibrotic agents, does not appear to offer any additional benefit in terms of first acute IPF exacerbation, first hospitalization for respiratory cause, or death. The cost for nerandomilast is $16,220 for a 30-day supply.

William T. Elliott, MD, FACP, is Assistant Clinical Professor of Medicine, University of California, San Francisco.

James Chan, PharmD, PhD, is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

References

1. Boehringer Ingelheim Pharmaceuticals, Inc. Jascayd prescribing information. October 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218764s000lbl.pdf

2. Richeldi L, Azuma A, Cottin V, et al. Nerandomilast in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2025;392:2193-2202.

3. Richeldi L, Azuma A, Cottin V, et al. Trial of a preferential phosphodiesterase 4B inhibitor for idiopathic pulmonary fibrosis. N Engl J Med. 2022;386:2178-2187.

4. Sauleda J, Nunez B, Sala E, Soriano JB. Idiopathic pulmonary fibrosis: Epidemiology, natural history, phenotypes. Med Sci (Basel). 2018;6(4):110.

5. Boehringer Ingelheim Pharmaceuticals, Inc. OFEV prescribing information. May 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/205832Orig1s016lbl.pdf

6. Legacy Pharma. Esbriet prescribing information. March 2025. https://esbriethcp.com/download/pdf/esbriet_prescribing.pdf

7. Finnerty JP, Ponnuswamy A, Dutta P, et al. Efficacy of antifibrotic drugs, nintedanib and pirfenidone, in treatment of progressive pulmonary fibrosis in both idiopathic pulmonary fibrosis (IPF) and non-IPF: A systematic review and meta-analysis. BMC Pulm Med. 2021;21:411.