Pooled analyses of phase III trials shows efficacy of Ofev (nintedanib) in idiopathic pulmonary fibrosis - Boehringer

Two post-hoc pooled analyses of the Phase III INPULSIS trials have been presented that further demonstrate the efficacy of Ofev (nintedanib), from Boehringer, in a range of people with idiopathic pulmonary fibrosis (IPF), regardless of disease severity at the start of the trials. Pooled analysis of the two Phase III INPULSIS trials investigated the efficacy of Ofev on disease progression in subgroups of patients defined by their GAP (gender, age, physiology) stage. GAP stage is a composite index developed to predict prognosis in patients with IPF. Based on the index, patients were categorized as either GAP stage I or II/III.

At baseline, 500 patients (nintedanib 304; placebo 196) were at GAP stage I, and 560 patients (nintedanib 334; placebo 226) were at GAP stage II/III. The analysis showed a similar reduction in disease progression with Ofev versus placebo regardless of GAP stage (no significant difference between GAP stage I versus GAP stage II/III). Disease progression was defined as an absolute decline in forced vital capacity (FVC) equal to or more than 5% predicted or death over 52 weeks.

In addition, treatment effect remained consistent between the two GAP subgroups when progression was measured as an absolute FVC decline at least 10% predicted or death over 52 weeks. A second post-hoc pooled analysis of the two INPULSIS trials investigated the effect of treatment on disease progression based on patients' baseline composite physiologic index (CPI), a newer measure that also reflects disease severity through the use of spirometric volumes and measures of gas transfer without radiologic scoring. Subgroup analyses were conducted of patients by baseline CPI of less than 45 versus more than 45, and less than 55 versus more than 55. A higher CPI score is associated with a worse prognosis. At baseline, 500 patients (nintedanib 304; placebo 196) were at GAP stage I, and 560 patients (nintedanib 334; placebo 226) were at GAP stage II/III. When using the baseline CPI threshold of 45, treatment effects were comparable based on the time to absolute decline in FVC of at least 5% predicted or death over 52 weeks (below 45 vs. above 45) or the time to absolute decline in FVC of at least 10% predicted or death over 52 weeks. Also, there were no significant differences in treatment effect when a baseline CPI threshold of 55 was used to define subgroups for time to absolute decline in FVC of at least 5% or death and for time to absolute decline in FVC of at least 10% or death. Results were presented at CHEST 2016.

Comment: Pirfenidone (Esbriet) from Intermune/Roche is a competitor to nintedanib and both Esbriet and Ofev are US and EU approved to treat Idiopathic Pulmonary Fibrosis.