Boehringer Ingelheim's investigational drug nerandomilast (BI 1015550) has demonstrated positive topline results in the Phase 3 FIBRONEER-IPF trial, marking a significant step forward in the treatment of idiopathic pulmonary fibrosis (IPF). The trial met its primary endpoint, showing a statistically significant improvement in lung function, as measured by forced vital capacity (FVC), in patients treated with nerandomilast compared to placebo over 52 weeks.
FIBRONEER-IPF Trial Details
The FIBRONEER-IPF trial (NCT05321069) is a double-blind, randomized, placebo-controlled study involving 1,177 adults aged 40 years and older with IPF across more than 30 countries. Participants were administered either 9 mg or 18 mg of nerandomilast twice daily, or a placebo, for at least 52 weeks. The primary endpoint was the absolute change from baseline in FVC at week 52.
Secondary endpoints included time to first acute IPF exacerbation, time to first respiratory cause hospitalization, and mortality. Boehringer Ingelheim plans to present detailed findings, including comprehensive efficacy and safety data, in the first half of 2025.
Nerandomilast: A Novel Approach
Nerandomilast is an oral, preferential inhibitor of phosphodiesterase 4B (PDE4B), an enzyme highly expressed in the lungs and believed to play a central role in inflammation and fibrosis. By selectively inhibiting PDE4B, nerandomilast aims to disrupt these pathways, exerting anti-fibrotic and anti-inflammatory effects on the lungs.
This mechanism of action differs from existing therapies like nintedanib (Ofev) and pirfenidone (Esbriet), both of which slow disease progression but have limitations in terms of side effect profiles and tolerability. The FDA granted nerandomilast Breakthrough Therapy designation in February 2022, highlighting its potential to address the unmet needs in IPF treatment.
Clinical Significance and Future Directions
IPF is a progressive and ultimately fatal lung disease characterized by scarring and inflammation of the lungs, leading to shortness of breath, fatigue, and reduced quality of life. It affects approximately 3 million people worldwide and has a high unmet need for more effective and better-tolerated treatments.
"This is the first IPF phase 3 trial in a decade to meet its primary endpoint," said Ioannis Sapountzis, PhD, head of global therapeutic areas at Boehringer Ingelheim, in a press release. "IPF has a high unmet need for patients, and we are continuously fostering our research activities to develop more options for one of the most common interstitial lung diseases."
Boehringer Ingelheim intends to submit a new drug application for nerandomilast to the FDA and other regulatory agencies based on the FIBRONEER-IPF results. The company is also evaluating nerandomilast in a Phase 3 trial (FIBRONEER-ILD) for progressive pulmonary fibrosis, further expanding its potential application in fibrotic lung diseases.
