Safety and Efficacy of BI 1015550, a Preferential Inhibitor of Phosphodiesterase 4B, in Patients with Idiopathic Pulmonary Fibrosis: a Phase 2 Trial* 

Rationale Phosphodiesterase (PDE) 4 inhibitors have both anti-inflammatory and antifibrotic effects. Preferential inhibition of specific subtypes may improve tolerability. BI 1015550 is an oral preferential inhibitor of PDE4B and candidate drug for the treatment of idiopathic pulmonary fibrosis (IPF). This randomized, double-blind, multicenter, Phase 2 study (NCT04419506) investigated the safety and efficacy of BI 1015550 in patients with IPF.

Methods Patients with FVC≥45% predicted, who had not received antifibrotic therapy (non-AF) or received a stable dose of AF for at least 8 weeks before study entry (AF) were randomized 2:1 to BI 1015550 18 mg bd or placebo for 12 weeks.

The primary endpoint was change from baseline in FVC (mL) at 12 weeks, evaluated separately in the non-AF and AF patient groups, based on a Bayesian borrowing approach using historical data to refine the estimate for the placebo arm (primary analysis), and a mixed model with repeated measurements (MMRM), which did not include historical data (sensitivity analysis).

Results A total of 147 patients (77% male, mean FVC 77.7% predicted) were randomized and treated with BI 1015550 (non-AF n=48; AF n=49) or placebo (non-AF n=25; AF n=25). In the Bayesian analysis, the median changes in FVC in the non-AF group were 5.7 mL (BI 1015550) and –81.7 mL (placebo) (median difference 88.4 mL, 99.8% probability that BI 1015550 is superior to placebo). In the AF group, these respective changes were 2.7 mL and –59.2 mL (median difference 62.4 mL, 98.6% probability that BI 1015550 is superior to placebo). Results were comparable by MMRM, with a larger decline in the placebo arm (Table). The proportion of patients with any adverse event (AE) was higher in patients treated with BI 1015550 compared with placebo in both non-AF (65% vs 52%) and AF patients (73% vs 68%). The most frequent AE was diarrhea; this was more common in patients treated with BI 1015550 than in placebo for both non-AF (17% vs 8%) and AF patients (31% vs 16%). Serious AEs and severe AEs were balanced in both groups ([Abb. 1]).

Abb. 1  Changes from baseline in FVC estimated using Bayesian Borrowing or MMRM

Conclusions Treatment with BI 1015550 at 18 mg BID preserved lung function in patients with IPF, when given alone or on top of AF. The tolerability profile of BI 1015550, in combination with the beneficial effects on FVC, warrants further study of BI 1015550 as a treatment for fibrotic ILDs.

Publication History

Article published online:
09 March 2023