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Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis
Luca Richeldi1, Arata Azuma2,3, Vincent Cottin4
1Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome.
Background:
Nerandomilast (BI 1015550) is an orally administered preferential inhibitor of phosphodiesterase 4B with antifibrotic and immunomodulatory effects. In a phase 2 trial involving patients with idiopathic pulmonary fibrosis, treatment with nerandomilast stabilized lung function over a period of 12 weeks.
Methods:
In this phase 3, double-blind trial, we randomly assigned patients with idiopathic pulmonary fibrosis 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 (nintedanib or pirfenidone vs. none). The primary end point was the absolute change from baseline in forced vital capacity (FVC), measured in milliliters, at week 52.
Results:
A total of 1177 patients underwent randomization, of whom 77.7% were taking nintedanib or pirfenidone at enrollment. Adjusted mean changes in FVC at week 52 were -114.7 ml (95% confidence interval [CI], -141.8 to -87.5) in the nerandomilast 18-mg group, -138.6 ml (95% CI, -165.6 to -111.6) in the nerandomilast 9-mg group, and -183.5 ml (95% CI, -210.9 to -156.1) in the placebo group. The adjusted difference between the nerandomilast 18-mg group and the placebo group was 68.8 ml (95% CI, 30.3 to 107.4; P<0.001), and the adjusted difference between the nerandomilast 9-mg group and the placebo group was 44.9 ml (95% CI, 6.4 to 83.3; P = 0.02). The most frequent adverse event in the nerandomilast groups was diarrhea, reported in 41.3% of the 18-mg group and 31.1% of the 9-mg group, as compared with 16.0% in the placebo group. Serious adverse events were balanced across trial groups.
Conclusions:
In patients with idiopathic pulmonary fibrosis, treatment with nerandomilast resulted in a smaller decline in the FVC than placebo over a period of 52 weeks. (Funded by Boehringer Ingelheim; FIBRONEER-IPF ClinicalTrials.gov number, NCT05321069.).
Insights
Nerandomilast demonstrated a slower decline in lung function for idiopathic pulmonary fibrosis patients over 52 weeks. This phosphodiesterase 4B inhibitor showed significant benefits compared to placebo in a large Phase 3 trial.
Area of Science:
- Pulmonology
- Pharmacology
- Clinical Trials
Background:
- Nerandomilast is an oral phosphodiesterase 4B inhibitor with demonstrated antifibrotic and immunomodulatory properties.
- Previous Phase 2 trials indicated that nerandomilast could stabilize lung function in idiopathic pulmonary fibrosis (IPF) patients over 12 weeks.
Purpose of the Study:
- To evaluate the efficacy and safety of nerandomilast in patients with idiopathic pulmonary fibrosis (IPF).
- To determine the effect of nerandomilast on the rate of lung function decline over a 52-week period.
Main Methods:
- A Phase 3, double-blind, randomized trial involving 1177 IPF patients.
- Patients were assigned 1:1:1 to receive 18 mg nerandomilast, 9 mg nerandomilast, or placebo twice daily.
- Stratification was based on background antifibrotic therapy (nintedanib/pirfenidone or none); primary endpoint was change in forced vital capacity (FVC) at 52 weeks.
Main Results:
- Nerandomilast treatment resulted in a smaller adjusted mean decline in FVC at 52 weeks compared to placebo (-114.7 ml for 18 mg, -138.6 ml for 9 mg vs. -183.5 ml for placebo).
- The differences were statistically significant: 68.8 ml (P<0.001) for the 18 mg group and 44.9 ml (P=0.02) for the 9 mg group versus placebo.
- Diarrhea was the most frequent adverse event (41.3% in 18 mg group, 31.1% in 9 mg group vs. 16.0% in placebo group); serious adverse events were balanced.
Conclusions:
- Nerandomilast significantly slowed the decline in forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis over 52 weeks compared to placebo.
- The findings support nerandomilast as a potential therapeutic option for managing IPF, with diarrhea as a notable side effect.
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