Source / Disclosures
Richelde L, et al. The New England Journal of Medicine And gamma Discussion on the Edge: Recently Published Pulmonary Research Reports. Presented at: International Conference of the American Thoracic Society. May 13-18, 2022; San Francisco (mixed meeting).
Richeldy has reported 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 – An oral preferential phosphodiesterase 4B inhibitor treatment prevented deterioration of lung function among patients with idiopathic pulmonary fibrosis, regardless of the background to antifibrotic therapy use.
A phase II trial included 147 adults with IPF who were randomly assigned to a preferential oral phosphodiesterase 4B (PDE4B) inhibitor (BI 1015550, Boehringer Ingelheim) at a dose of 18 mg or placebo twice daily. Treatment was continued for 12 weeks, followed by a one-week follow-up period.
Treatment with a PDE4B inhibitor appears to stabilize lung function regardless of the background of antifibrotic therapy, while lung function in the placebo group significantly decreased, according to results presented at the International Conference of the American Thoracic Society and published at the same time in The New English Journal of Medicine.
Among those not on background antifibrotic therapy, the mean change in forced vital capacity from baseline to 12 weeks was 5.7 ml (95% CI) [CrI]from 39.1 to 50.5) in the PDE4B inhibitor group compared to -81.7 ml (95% CrI, -133.5 to -44.8) in the placebo group (probability of 0.998 that BI 1015550 was better than placebo), Luca RicheldyMasters, PhD, From Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, during a presentation.
Among those in the background nintedanib (Ofev, Boehringer Ingelheim) or pirfenidone, the mean 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 (a 0.986 probability that BI 1015550 was better than placebo), Richeldy said.
The results of Bayesian analysis were consistent in a mixed model with repeated measures, according to Richeldy.
At 12 weeks, adverse events occurred in 65% of the treatment group compared to 52% of the placebo group. Among those treated in the background, the incidence was 73% versus 68%, respectively. Diarrhea occurred in 17% of patients in the PDE4B inhibitor group who were not treated in the background and in 31% of patients in the background. Diarrhea occurred most frequently in the treatment group regardless of the background to antifibrotic therapy. Thirteen patients discontinued the study due to adverse events. Of these, 10 patients were receiving anti-fibrotic therapy.
Patients enrolled in the trial were 40 years of age and older with a diagnosis of IPF. Most of them were men, the average age was about 70 years and more than three-quarters of them were white. Patients can continue to take nintedanib or pirfenidone if they have been on a stable dose for at least 8 weeks before the examination. Among the background-treated patients, nintedanib was used by 53% of patients assigned a PDE4B inhibitor and 68% to a placebo assigned, while 46.9% and 32%, respectively, were on pirfenidone.
Currently, there are two approved anti-fibrotic drugs [for IPF] – nintedanib and pirfenidone – which slow the progression of fibrosis but do not stop it. “There is an unmet clinical need for additional therapies that can be used alone or in combination with existing anti-inflammatory therapies,” Richeldy said.
A phase II double-blind, placebo-controlled, parallel-controlled trial was conducted at 90 sites in 22 countries from August 2020 to October 2021.
“The observed safety and tolerability of BI 1015550 was acceptable, and combined with the beneficial effects on FVC, warranted further clinical development as a treatment for IPF and other forms of progressive pulmonary fibrosis,” Richeldy said during the session.