Oral pirfenidone (PFD) is a small synthetic non-peptide molecule with antifibrotic and anti-inflammatory properties in experimental models. Preliminary clinical studies in idiopathic pulmonary fibrosis (IPF) have shown promise.
Patients with pulmonary fibrosis were randomized (1:1) to receive oral PFD (40 mg/kg/d) or prednisone (PDN; 0.33 mg/kg/d) in a double-blind, multicenter trial. Entry requirements included VC, TLC, DLCO, and FEV1 >= 35% and O2saturation >= 75%. Pulmonary function tests and 6MWT were performed every 3 months. All patients with IPF with >= 1 post-baseline measurement were analyzed for efficacy (N=44). Safety analysis included all enrolled patients who received >= 1 dose of study drug (N=52).
Fifty-three patients were enrolled, of whom 46 had IPF. Mean age = 65 years; mean baseline FVC = 57%; mean duration of treatment ∼ 1 year. Fifty-seven percent of patient completed 12 months of treatment. Results are presented in Table 1
Results Mean Change from Baseline at 12 Months(1)Pirfenidone (N=24)Prednisone (N=20)p ValueDistance walked, 6-min walk test (6MWT) [meters]−12.8−72.50.1Minimum O2 saturation in 6MWT (%)1.8−2.90.01% FVC−4.2−7.30.2% TLC−5.3−4.20.8A-a gradient−0.24.40.3(1) last observation carried forward.Ten patients died (5 PFD, 5 PDN). Treatment was discontinued due to an adverse event in 5 patients (2 PFD, 3 PDN). Nausea, weight loss, and dyspepsia were the most commonly reported side effects in PFD patients, while increased weight was most frequent in PDN patients.CONCLUSIONS: The tolerability of PFD, as well as the efficacy results from the 6MWT and other physiologic measures, are encouraging and warrant further study.
These data suggest possible utility of oral PFD in the treatment of IPF.
S. Moises, InterMune, Inc., Grant monies.