A preferential phosphodiesterase 4 inhibitor (PDE4B) has shown promise in preventing lung function decline in patients with IPF in an international study including an Australian site.
A phase 2 RCT, published in the NEJM and presented at ATS 2022, compared an oral investigational product BI 101555 with placebo in 147 patients with IPF.
Patients already established on a stable dose of nintedanib or pirfenidone were permitted to continue their antifibrotic therapy.
In the primary endpoint, there was a significant difference in the FVC change from baseline to 12 weeks with the PDE4B inhibitor than placebo (5.7 ml v -81.7 ml) in patients without background antifibrotic therapy.
“Among patients with background antifibrotic use, the respective FVC changes were 2.7 ml (95% credible interval, –32.8 to 38.2) and –59.2 ml (95% credible interval, –111.8 to –17.9) (median difference, 62.4 ml; 95% credible interval, 6.3 to 125.5; probability that BI 1015550 was superior to placebo, 0.986).”
The study found the change in the percentage of the predicted value for DLCO was similar in the two trial groups at 12 weeks in patients without background antifibrotic use (adjusted mean difference of 0.8 percentage points (95% CI, –3.5 to 5.0).
Among patients with background anti-fibrotic use, the adjusted mean difference between the trial groups was 2.8 percentage points (95% CI,–0.4 to 5.9).
The adjusted mean changes in the Living with Pulmonary Fibrosis (L-PF) total score for quality of life from baseline to week 12 were similar across the trial groups regardless of background antifibrotic use
“Treatment with BI 1015550 appeared to stabilise lung function regardless of whether patients were receiving a background antifibrotic agent, in contrast to the placebo group, in which there was a marked decrease in the FVC,” the authors wrote.
The study found gastrointestinal disorders were the most common adverse event and more common with treatment than placebo (27% v 16% without background antifibrotic use; 37% v 32% with background antifibrotic use).
Most cases of diarrhoea were mild but in five patients the adverse events led to treatment discontinuation.
The study authors noted that preclinical toxicology studies have linked PDE4 inhibitors with vasculitis however there was only one unconfirmed case reported as “suspected IPF exacerbation and suspected vasculitis”
“It will be important to evaluate vasculitis as an adverse event of special interest in phase 3 trials of BI 1015550, “ the researchers said.
The study was supported by Boehringer Ingelheim.