Efficacy/Safety of Idiopathic Pulmonary Fibrosis Treatment With BI 1015550

In patients with idiopathic pulmonary fibrosis (IPF), treatment with the preferential phosphodiesterase 4B (PDE4B) inhibitor BI 1015550, either alone or with background use of an antifibrotic agent, prevented a decrease in lung function, according to clinical trial results recently published in The New England Journal of Medicine. Notably, BI 1015550, an oral preferential inhibitor of the phosphodiesterase 4 (PDE4B) subtype, was recently granted FDA Breakthrough Therapy designation.

Previous research has suggested that BI 1015550 has an anti-inflammatory and antifibrotic effect. To test this, researchers for the current study conducted a phase 2, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov identifier: NCT04419506) to explore the efficacy and safety of BI 1015550.

Study participants were randomly assigned in a 2:1 ratio to BI 1015550 18 mg twice daily or placebo. The primary study endpoint was change from baseline in forced vital capacity (FVC) at 12 weeks. The secondary endpoint was percentage of patients with adverse events (AEs) during the treatment period, which included the 1-week follow-up. Change from baseline in percentage of predicted value of the diffusing capacity of the lungs for carbon monoxide, corrected for hemoglobin level, was evaluated as well.

Patients underwent screening between August 12, 2020, and October 15, 2021. A total of 147 individuals were randomized to either BI 1015500 or placebo. Of these participants, 49 of those treated with BI 1015500 and 25 of those treated with placebo received a background antifibrotic agent as well. Additionally, 48 of participants were treated with BI 1015500 and 25 of participants were treated with placebo without background antifibrotic use.

Among participants without any background antifibrotic use, the median change in FVC was 5.7 mL (95% credible interval, –39.1 to 50.5) in the BI 1015500 arm vs –81.7 mL (95% credible interval, –133.5 to –44.8) in the placebo arm (median difference, 88.4 mL; 95% credible interval, 29.5 to 154.2; probability that BI 1015500 was superior to placebo, 0.998).

In contrast, in participants with background antifibrotic use, the median change in FVC was 2.7 mL (95% credible interval, –32.8 to 38.2) in the BI 1015500 arm vs –59.2 mL (95% credible interval, –111.8 to –17.9) in the placebo arm (median difference, 62.4 mL; 95% credible interval, 6.3 to 125.5; probability that BI 1015500 was superior to placebo, 0.986).

The most commonly reported AE was diarrhea. Overall, 13 patients discontinued treatment with BI 1015500 because of AEs. The proportions of patients with serious AEs or severe AEs were similar in the 2 treatment groups.

Major limitations of the current trial include its relatively small sample size and 12-week duration.  These factors did not allow for the meaningful collection of data related to clinically important events, such as acute exacerbations or death, or determination in patients’ quality-of-life measures.

“The safety profile of BI 1015500, in combination with the observed effects on the FVC, warrants further research as a treatment for IPF and other forms of progressive pulmonary fibrosis,” the investigators concluded.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference  

Richeldi L, Azuma A, Cottin V, et al; 1305-0013 Trial Investigators. Trial of a preferential phosphodiesterase 4B inhibitor for idiopathic pulmonary fibrosis. N Engl J Med. 2022; 386(23):2178-2187. doi:10.1056/NEJMoa2201737