Boehringer Ingelheim is moving forward with regulatory submissions for nerandomilast following the success of its Phase III FIBRONEER-IPF trial. The study met its primary endpoint, demonstrating a statistically significant improvement in forced vital capacity (FVC) – a key measure of lung function – in patients with idiopathic pulmonary fibrosis (IPF) after 52 weeks of treatment.
The FIBRONEER-IPF trial (NCT05321069) enrolled 1,177 patients diagnosed with IPF, randomizing them to receive either nerandomilast or a placebo twice daily. Boehringer Ingelheim plans to release comprehensive efficacy and safety results from the trial in the first half of 2025.
Nerandomilast's Potential Impact on IPF Treatment
Boehringer Ingelheim emphasized that the Phase III trial of nerandomilast is the first successful late-stage IPF trial in a decade to meet its primary endpoint. The company already markets Ofev (nintedanib), a tyrosine kinase inhibitor (TKI) approved by the FDA in 2014 for IPF treatment. Ofev generated €3.5 billion ($3.89 billion) in global sales last year and has since been approved for interstitial lung disease associated with systemic sclerosis or scleroderma (SSc-ILD) and chronic interstitial lung disease.
Trial Design and Endpoints
The primary endpoint of the FIBRONEER-IPF trial was the change in FVC from baseline after 52 weeks. Secondary endpoints included time to first acute IPF exacerbation, first hospitalization for respiratory cause, or death.
Nerandomilast functions as a preferential inhibitor of phosphodiesterase 4B (PDE4B). The FDA granted it breakthrough therapy designation for IPF treatment in 2022. Boehringer Ingelheim is also evaluating nerandomilast in a Phase III trial (FIBRONEER-ILD, NCT05321082) for patients with progressive fibrosing interstitial lung diseases, with completion expected by the end of this year.
Addressing Unmet Needs in IPF
IPF presents a significant unmet medical need, with only two FDA-approved medications currently available: Ofev and Roche’s Esbriet (pirfenidone). While Esbriet also gained FDA approval in 2014, its profits have declined due to the introduction of generics. Roche reported sales of CHF718 million ($752 million) in 2022, which decreased to CHF202 million ($239 million) last year.
Several other therapies for IPF are in Phase II clinical trials. Vicore Pharma's Phase IIa trial of buloxibutid, an angiotensin II type 2 receptor (AT2R) agonist, met both primary and secondary endpoints. Bridge Biotherapeutics anticipates reporting topline data in the first half of 2025 from its Phase II trial evaluating BBT-877, an autotoxin inhibitor, in IPF.
