Nerandomilast Approval Expands Treatment Options for PPF, With Shervin Assassi, MD

The recent US Food and Drug Administration approval of Boehringer Ingelheim’s nerandomilast (Jascayd) tablets for the treatment of progressive pulmonary fibrosis (PPF) in adults marks a significant advancement for a disease that has historically had very limited treatment options.

The approval makes nerandomilast the first and only preferential phosphodiesterase 4B (PDE4B) inhibitor with immunomodulatory and antifibrotic effects approved in this indication and was based on results from the phase 3 FIBRONEERTM-ILD clinical trial, the largest clinical trial program in PPF to date.

“Until now, there was only 1 medication that is FDA approved for progressive pulmonary fibrosis,” Shervin Assassi, MD, director of the division of rheumatology at McGovern Medical School, UTHealth Houston, explained to HCPLive. “Immunosuppressive agents are used for treating ILDs in certain settings, but until now, if those medications were not sufficient to control patients’ underlying ILD we didn't have any other options. Nerandomilast expands that armamentarium, and I think it's an excellent addition to our therapeutic options.”

The preferential PDE4B inhibitor’s approval in PPF was based on results from the phase 3 FIBRONEER-ILD clinical trial in which patients with idiopathic pulmonary fibrosis were randomly assigned in a 1:1:1 ratio to receive nerandomilast at a dose of 18 mg twice daily, nerandomilast at a dose of 9 mg twice daily, or placebo, with stratification according to background antifibrotic therapy with nintedanib or pirfenidone versus none. The primary endpoint was the absolute change from baseline in Forced Vital Capacity (FVC), a measure of lung function, in mL at week 52.

Results showed nerandomilast demonstrated a significantly smaller reduction in FVC decline from baseline compared to placebo. The adjusted mean decline in absolute change from baseline in FVC in patients receiving nerandomilast 18 mg or 9 mg was -86 mL and -69 mL, respectively, versus -152 mL in the placebo group.

While there was no statistically significant difference for the key secondary composite endpoint of time to first acute ILD exacerbation, hospitalization for respiratory cause, or death, exploratory analyses suggested clinically meaningful trends. Nerandomilast 18 mg showed a nominally significant reduction in the risk of acute ILD exacerbations over the blinded trial duration compared to placebo (HR, 0.60; 95% CI, 0.38 to 0.94) as well as a numerical reduction in the risk of hospitalization for respiratory cause over the blinded trial duration compared to placebo (HR, 0.82; 95% CI, 0.61 to 1.11). An additional prespecified analysis of overall survival at the end of the FIBRONEER-ILD trial showed a trend in favor of nerandomilast.

“What is so important to keep in mind is that progressive pulmonary fibrosis is not just one diagnosis. There are multiple underlying diagnoses that lead to this similar downstream picture, which is basically pulmonary fibrosis,” Assassi told HCPLive. “What was special here is that the results are consistent across all these diagnoses.”

He added that efficacy was observed across both treatment doses and regardless of background antifibrotic therapy, suggesting that nerandomilast could be used across different ILDs and may be particularly valuable for patients at high risk of progression.

Safety was another key component of nerandomilast and the FIBRONEER-ILD trial data that Assassi highlighted, noting similar rates of side effects and overall tolerability between the treatment and placebo groups.

“I think it's important to point out that the FIBRONEER-ILD trial is going after the concept that a scar is a scar, regardless of the divergent upstream diagnosis. Basically, once we have lung fibrosis, if you have an effective treatment, in this case, a preferential PDE4B inhibitor, that effective treatment will treat lung fibrosis regardless of what the upstream diagnosis is” Assassi said. “It brings rheumatology and pulmonary medicine together and helps us understand these diseases from a different perspective, but also encourages us to work together, which will ultimately benefit our patients in terms of longer survival and better quality of life.”

Editors’ Note: Assassi reports relevant disclosures with Boehringer Ingelheim, Janssen, Novartis, AbbVie, CSL Behring, and AstraZeneca.

References

1. Brooks A. FDA Approves Nerandomilast (Jascayd) Tablets for Progressive Pulmonary Fibrosis. HCPLive. December 19, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/fda-approves-nerandomilast-jascayd-tablets-for-progressive-pulmonary-fibrosis

2. Richeldi L, Azuma A, Cottin V, et al. Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med. doi:10.1056/NEJMoa2414108