Boehringer Ingelheim’s investigational drug Nerandomilast (BI 1015550) has achieved its primary endpoint in the Phase III FIBRONEER-ILD clinical trial, demonstrating potential as a new treatment for progressive pulmonary fibrosis (PPF).
This marks a significant step in the development of therapies for fibrotic lung diseases, which remain a major unmet medical need worldwide.
This article provides a detailed overview of Nerandomilast’s mechanism of action, clinical trial results, and its potential impact on the treatment landscape for PPF.
1. Understanding Progressive Pulmonary Fibrosis (PPF)
- 1.1 What Is Progressive Pulmonary Fibrosis?
- Progressive Pulmonary Fibrosis (PPF) is a distinct clinical form observed in interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). It is characterized by progressive fibrotic changes in the lungs, regardless of the underlying disease.
- PPF is defined based on clinical symptoms, lung function decline, and high-resolution computed tomography (HRCT) imaging findings, rather than the specific underlying ILD diagnosis.
- Unlike IPF, which has FDA-approved therapies (nintedanib and pirfenidone), many non-IPF fibrotic lung diseases lack effective treatment options.
- 1.2 The Unmet Medical Need in PPF
- Current therapies for pulmonary fibrosis, including antifibrotic agents, slow disease progression but do not reverse lung damage. Patients with non-IPF progressive fibrosis often experience a rapid decline in lung function, highlighting the urgent need for novel treatments that can more effectively target the disease.
2. Nerandomilast: A Novel PDE4B Inhibitor for PPF
- 2.1 Mechanism of Action
- Nerandomilast (BI 1015550) is a selective phosphodiesterase 4B (PDE4B) inhibitor. PDE4 enzymes regulate inflammatory and fibrotic pathways, playing a critical role in the progression of lung fibrosis. Nerandomilast was granted FDA Breakthrough Therapy Designation for the treatment of IPF in February 2022.
3. The FIBRONEER-ILD Phase III Trial (NCT05321082)
- 3.1 Study Design and Objectives
- The FIBRONEER-ILD Phase III trial was a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of Nerandomilast in patients with progressive pulmonary fibrosis.
- Primary Endpoint: Absolute change from baseline in Forced Vital Capacity (FVC) (mL) at Week 52.
- Secondary Endpoints: Time to first acute ILD exacerbation, first hospitalization for respiratory cause, or death over the duration of the trial
- 3.2 Positive Results: Nerandomilast Meets Its Primary Endpoint
- The trial demonstrated that Nerandomilast met its primary endpoint, which was the absolute change from baseline in forced vital capacity [mL] at week 52 versus placebo.
- The FIBRONEER™-ILD trial marks the second Phase III study where the investigational drug nerandomilast has successfully achieved its primary endpoint.
- All efficacy and safety data from FIBRONEER™-ILD will be shared in the second quarter of 2025
- These results support Nerandomilast’s potential as a new treatment for patients with progressive pulmonary fibrosis, a group that currently has limited therapeutic options.
