Richeldi L, et al. The New England Journal of Medicine and JAMA Discussion on the Edge: Reports of Recently Published Pulmonary Research. Presented at: American Thoracic Society International Conference; May 13-18, 2022; San Francisco (hybrid meeting).
Disclosures: Richeldi reports financial relationships with Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipla, CSL Behring, FibroGen, Nitto, Pliant Therapeutics, Promedior, Respivant, Roche, Toray and Zambon.
SAN FRANCISCO — Treatment with an oral preferential phosphodiesterase 4B inhibitor prevented lung function decline among patients with idiopathic pulmonary fibrosis, regardless of background antifibrotic therapy use.
The phase 2 trial enrolled 147 adults with IPF who were randomly assigned to an oral preferential inhibitor of the phosphodiesterase 4B (PDE4B) subtype (BI 1015550, Boehringer Ingelheim) at a dose of 18 mg or placebo twice daily. Treatment continued for 12 weeks, followed by a 1-week follow-up period.
Treatment with the PDE4B inhibitor appeared to stabilize lung function regardless of background antifibrotic therapy, whereas lung function in the placebo group was markedly reduced, according to results presented at the American Thoracic Society International Conference and simultaneously published in The New England Journal of Medicine.
Among those not on background antifibrotic therapy, median change in FVC from baseline to 12 weeks was 5.7 mL (95% credible interval) [CrI]–39.1 to 50.5) in the PDE4B inhibitor group compared with –81.7 mL (95% CrI, –133.5 to –44.8) in the placebo group (0.998 probability that BI 1015550 was superior to placebo), Luca richeldiMD, PhD, from Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Universit Cattolica del Sacro Cuore, Rome, said during a presentation.
Among those on background nintedanib (Ofev, Boehringer Ingelheim) or pirfenidone, median change in FVC at 12 weeks was 2.7 mL (95% CrI, –32.8 to 38.2) in the PDE4B inhibitor group compared with –59.2 mL (95% CrI, – 111.8 to –17.9) in the placebo group (0.986 probability that BI 1015550 was superior to placebo), Richeldi said.
Results of the Bayesian analysis were consistent in a mixed model with repeated measures, according to Richeldi.
At 12 weeks, adverse events occurred in 65% of the treatment group compared with 52% of the placebo group. Among those on background therapy, the incidence was 73% vs. 68%, respectively. Diarrhea occurred in 17% of patients in the PDE4B inhibitor group not on background therapy and in 31% on background therapy. Diarrhea occurred more frequently in the treatment group regardless of background antifibrotic therapy use. Thirteen patients discontinued the study due to adverse events; of those, 10 patients were receiving background antifibrotic therapy.
Patients enrolled in the trial were aged 40 years and older with diagnosed IPF. Most were men, the mean age was about 70 years and more than three-quarters were white. Patients could continue nintedanib or pirfenidone if they were on a stable dose for at least 8 weeks before screening. Among patients on background therapy, nintedanib was used by 53% of patients assigned the PDE4B inhibitor and 68% assigned placebo, whereas 46.9% and 32%, respectively, were on pirfenidone.
“Currently, there are two approved antifibrotic drugs [for IPF] — nintedanib and pirfenidone — which slow but do not stop progression of fibrosis. There is an unmet clinical need for additional treatments that can be used alone or in combination with the existing antifibrotic therapies,” Richeldi said.
The double-blind, placebo-controlled, parallel, phase 2 trial was conducted at 90 sites in 22 countries from August 2020 to October 2021.
“The observed safety and tolerability of BI 1015550 were acceptable and, in combination with the beneficial effects on FVC, warrant further clinical development as a treatment for IPF and other forms of progressive pulmonary fibrosis,” Richeldi said during the session.