Rare diseases Xagena

Xagena Mappa
Xagena Newsletter

Idiopathic pulmonary fibrosis: Pirfenidone reduces disease progression

In two of three phase 3 trials, Pirfenidone ( Esbriet ), an oral antifibrotic therapy, reduced disease progression, as measured by the decline in forced vital capacity ( FVC ) or vital capacity, in patients with idiopathic pulmonary fibrosis; in the third trial, this end point was not achieved.

The aim of the study was to confirm the beneficial effect of Pirfenidone on disease progression in such patients.

In this phase 3 study, researchers have randomly assigned 555 patients with idiopathic pulmonary fibrosis to receive either oral Pirfenidone ( 2403 mg per day ) or placebo for 52 weeks.

The primary end point was the change in forced vital capacity or death at week 52. Secondary end points were the 6-minute walk distance, progression-free survival, dyspnea, and death from any cause or from idiopathic pulmonary fibrosis.

In the Pirfenidone group, as compared with the placebo group, there was a relative reduction of 47.9% in the proportion of patients who had an absolute decline of 10 percentage points or more in the percentage of the predicted forced vital capacity or who died; there was also a relative increase of 132.5% in the proportion of patients with no decline in forced vital capacity ( P less than 0.001 ).

Pirfenidone has reduced the decline in the 6-minute walk distance ( P=0.04 ) and has improved progression-free survival ( P less than 0.001 ).

There was no significant between-group difference in dyspnea scores ( P=0.16 ) or in rates of death from any cause ( P=0.10 ) or from idiopathic pulmonary fibrosis ( P=0.23 ).

However, in a prespecified pooled analysis incorporating results from two previous phase 3 trials, the between-group difference favoring Pirfenidone was significant for death from any cause ( P=0.01 ) and from idiopathic pulmonary fibrosis ( P=0.006 ).

Gastrointestinal and skin-related adverse events were more common in the Pirfenidone group than in the placebo group but rarely led to treatment discontinuation.

In conclusion, Pirfenidone, as compared with placebo, has reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with idiopathic pulmonary fibrosis.
Treatment was associated with an acceptable side-effect profile and fewer deaths. ( Xagena )

King TE et al, N Engl J Med 2014; 370:2083-2092