Boehringer's nerandomilast achieves primary goal in phase-III FIBRONEER™-IPF study

On September 16, 2024, Boehringer Ingelheim, based in INGELHEIM, Germany, announced that the FIBRONEER™-IPF trial achieved its primary objective. The primary endpoint was the absolute change from baseline in Forced Vital Capacity (FVC) at week 52 compared to a placebo. FVC is an essential parameter for evaluating lung function.

Following these promising results, Boehringer Ingelheim plans to file a new drug application for nerandomilast with the US Food & Drug Administration (FDA) and other health authorities globally. The FDA had already given it Breakthrough Therapy Designation for idiopathic pulmonary fibrosis (IPF) in 2022.

Ioannis Sapountzis, Head of Global Therapeutic Areas at Boehringer Ingelheim, remarked, "This is the first IPF phase-III trial in a decade to meet its primary endpoint." He emphasized that the milestone is significant in their ongoing research and commitment to addressing IPF, a disease with substantial unmet patient needs.

Nerandomilast is an oral investigational phosphodiesterase 4B (PDE4B) inhibitor. Since it has not yet been approved for use, its safety and efficacy remain unconfirmed. It is being tested as part of the FIBRONEER™ global program, which includes two Phase III studies—FIBRONEER™-IPF and FIBRONEER™-ILD, the latter targeting Progressive Pulmonary Fibrosis (PPF).

The FIBRONEER™-IPF study (NCT05321069) is a double-blind, randomized, placebo-controlled trial. The study evaluates the efficacy and safety of nerandomilast over at least 52 weeks in patients with IPF. The trial's key secondary endpoint involves the time to the first occurrence of specific composite components: the first acute IPF/PPF exacerbation, first hospitalization for respiratory causes, or death.

Participants in the FIBRONEER™-IPF trial were divided into three groups randomly. Two groups received different doses of nerandomilast, while the third group was given a placebo. Conducted across more than 30 countries, the trial randomized 1,177 patients.

The FIBRONEER™ clinical program encompasses two Phase III randomized, double-blind, placebo-controlled trials: FIBRONEER™-IPF (NCT05321069) and FIBRONEER™-ILD (NCT05321082). These trials aim to investigate the efficacy, safety, and tolerability of nerandomilast over at least 52 weeks in patients with IPF and those with PPF.

In the FIBRONEER™-IPF trial, patients took either 9 mg or 18 mg doses of nerandomilast twice daily, or a placebo, for at least 52 weeks. The 18 mg twice-daily dose was supported by Phase II study results, and an additional 9 mg twice-daily dose was included to evaluate the benefit-risk balance at a lower dose.

Nerandomilast (BI 1015550) is an investigational oral preferential inhibitor of PDE4B, studied as a potential treatment for both IPF and PPF. It was granted FDA Breakthrough Therapy Designation for IPF treatment in February 2022. The compound’s efficacy, safety, and tolerability were previously studied in a Phase II randomized, double-blind, placebo-controlled trial involving 147 IPF patients. The primary endpoint was the change from baseline in FVC over 12 weeks.

IPF is one of the more prevalent forms of progressive fibrosing interstitial lung diseases (ILDs). Symptoms can include breathlessness during activity, a persistent dry cough, chest discomfort, fatigue, and weakness. Although classified as "rare," IPF affects around 3 million people globally, predominantly those over 50 years old, with a higher incidence in men.

In addition to IPF, patients with other types of fibrosing ILDs may develop a progressive phenotype known as progressive pulmonary fibrosis (PPF), characterized by worsening respiratory symptoms and radiological evidence of disease progression.