FIBRONEER-IPF Trial of Nerandomilast Meets Primary End Point

In a significant breakthrough for the treatment of idiopathic pulmonary fibrosis (IPF), Boehringer Ingelheim announced its investigational drug, nerandomilast (BI 1015550), has successfully met the primary end point in the pivotal phase 3 FIBRONEER-IPF trial.¹

The main end point in the study was lung function based on absolute change from baseline in forced vital capacity (FVC) at week 52 vs a placebo. The achievement marks the first such success in a decade, signaling a potential new treatment option for a condition that currently has limited pharmaceutical interventions.

Boehringer Ingelheim plans to submit a new drug application for nerandomilast based on the positive trial results | Image credit: MichaelVi – stock.adobe.com

“This announcement is not just a milestone for us at Boehringer Ingelheim but a beacon of hope for the 3 million people worldwide living with idiopathic pulmonary fibrosis,” Ioannis Sapountzis, PhD, head of global therapeutic areas at Boehringer Ingelheim, posted to LinkedIn.² “IPF is considered a rare disease, yet the burden on the individual and those around them is far from small. Through our growing understanding of the condition, we are able to streamline our research with the aim of fulfilling the unmet needs of those living with IPF.”

Boehringer Ingelheim plans to submit a new drug application for nerandomilast to the FDA and other global regulators based on the positive trial results.¹ The company is also conducting a second phase 3 study on progressive pulmonary fibrosis, FIBRONEER-ILD.

Currently, IPF treatment options are limited to nintedanib (Ofev) and pirfenidone (Esbriet), both of which can slow disease progression. Nerandomilast, which inhibits the enzyme phosphodiesterase 4B (PDE4B), is poised to offer a novel mechanism of action that could outperform existing therapies. Boehringer Ingelheim’s decision to advance this drug into a phase 3 trial, launched in 2022, is a key step toward addressing the unmet needs of patients with IPF, many of whom experience significant declines in lung function over time.

The FIBRONEER-IPF trial included 1177 participants with IPF across more than 30 countries. They were divided into 3 groups, taking a dose of nerandomilast 9 mg, nerandomilast 18 mg, or placebo twice daily. The primary end point was absolute change in FVC—a key measure of lung function—from baseline to week 52.

After 52 weeks, patients taking either dose of nerandomilast exhibited better performance on the FVC test compared with those taking placebo. This positive result led the trial to meet its primary end point, although specific data on lung function improvement, including FVC scores, has yet to be released. Boehringer Ingelheim said it is holding back full data on both efficacy and safety until the first half of 2025. Despite the limited release of data, nerandomilast’s potential to improve lung function and slow disease progression more effectively than current therapies is generating excitement.

“This is the first IPF phase 3 trial in a decade to meet its primary end point,” Sapountzis said in the news release. “Today’s announcement represents the next step in our long history in the research of this disease. 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.”

Although nerandomilast has not yet been approved for use, it received an FDA breakthrough therapy designation for IPF in February 2022.³ Its efficacy, safety, and tolerability were initially assessed in a phase 2 trial involving 147 patients with IPF, where lung function was measured over 12 weeks.

The FIBRONEER-IPF study’s scope goes beyond lung function improvement.¹ Secondary end points included time to hospitalization or death, but Boehringer Ingelheim has yet to disclose these findings. The trial also included patients both on and off stable therapy with nintedanib or pirfenidone, raising questions about how nerandomilast performs as a monotherapy vs in combination with existing drugs.

References

1. Boehringer’s nerandomilast meets primary endpoint in pivotal phase-III FIBRONEER™-IPF study. News release. Boehringer Ingelheim. September 16, 2024. Accessed September 18, 2024. https://www.boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/nerandomilast-primary-endpoint-phase-3-fibroneer-ipf
2. Ioannis Sapountzis. “This announcement is not just a milestone for us at Boehringer Ingelheim but a beacon of hope for the 3 million people worldwide living with idiopathic pulmonary fibrosis (IPF)…” LinkedIn. September 16, 2024. Accessed September 18, 2024. https://www.linkedin.com/feed/update/urn:li:activity:7241426057046683649/
3. FDA grants BI 1015550 breakthrough therapy designation for idiopathic pulmonary fibrosis. News release. Boehringer Ingelheim. February 24, 2022. Accessed September 18, 2024. https://www.boehringer-ingelheim.com/us/human-health/lung-diseases/pulmonary-fibrosis/fda-grants-bi-1015550-breakthrough-therapy