ATS 2022: The investigational PDE4B inhibitor slowed pulmonary decline in patients with IPF, both alone and with background use of approved antifibrotics.
New phase 2 data from Boehringer Ingelheim (BI) show promise for BI 1015550 - a novel investigational oral phosphodiesterase 4B (PDE4B) inhibitor that appears to slow lung function decline in persons with idiopathic pulmonary fibrosis (IPF).
The findings were simultaneously presented at the American Thoracic Society International Conference and published in the New England Journal of Medicine, according to a BI press statement.
The study, led by Luca Richeldi, MD, PhD, professor of respiratory medicine at the Università Cattolica del Sacro Cuore in Rome, Italy, was a phase II randomized, double-blind, placebo-controlled trial (NCT04419506) to investigate the efficacy and safety of oral BI 1015550, 18 mg twice daily, in patients with IPF.
A total of 147 patients (77% men) with forced vital capacity (FVC) ≥45% predicted (mean FVC 77.7% predcited) were randomized 2:1 to receive either BI 1015550 18 mg twice daily or placebo for 12 weeks, according to the study. Patients were either not taking antifibrotic therapy or were on a stable dose of antifibrotic therapy for at least 8 weeks before study entry.
The primary endpoint was change from baseline in FVC at week 12 (evaluated separately using Bayesian analysis according to use or nonuse of an antifibrotic agent). The secondary endpoint was the proportion of patients with treatment-emergent adverse events during the trial.
The median change in FVC in patients who were not on approved antifibrotics was +5.7 mL for BI 1015550 and -81.7 mL for placebo. Among patients on a stable background dose of antifibrotic therapy, median change in FVC was +2.7 mL for BI 1015550 and -59.2 mL for patients receiving placebo.
According to study authors, there is >98% probability that BI 1015550 was superior to placebo in reducing the rate of lung function decline in people with IPF.
The most frequently reported adverse event was diarrhea, according to the results, and discontinuation of the study drug by 13 patients was related to adverse events. The study also says that adverse or severe adverse events were equally distributed across the 2 trial groups.
"These encouraging, early data showed treatment with BI 1015550 slowed the rate of lung function decline in patients who were not on approved antifibrotics, as well as those who were taking existing antifibrotic therapy," commented principal investigator Richeldi in the BI statement.
"The Phase II results reinforce our confidence in BI 1015550, which will be accelerated into a pivotal Phase III program," said Carinne Brouillon, a member of the board of managing directors and head of human pharma at BI, in the statement. "We will work with regulatory agencies and scientific communities to potentially bring the next generation of treatments to people living with pulmonary fibrosis as quickly as possible."
The US Food and Drug Administration in February 2022 granted BI 1015550 breakthrough therapy designation. According to the BI statement, the company will initiate a phase 3 trial program to continue investigating the safety and efficacy of the PDE4B inhibitor in persons with IPF as well as other types of progressive pulmonary fibrosis.
Reference: Richeldi L, Azuma A, Cottin V, et al. Trial of a preferential phosphodiesterase 4B inhibitor for idiopathic pulmonary fibrosis. N Engl J Med. Published online May 15, 2022.