Pirfenidone - A Promising Option in the treatment of IPF

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and ultimately fatal disease, resulting in gradual decline of lung function for which there is no known cause or cure.  It is characterized by dyspnea. IPF is associated with a poor prognosis with paucity of treatments. The estimated median survival is 2-5 years. Hence, there is a need for the development of novel drugs which can arrest the loss of lung function. The CAPACITY (Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis) program is a combination of 2 multinational trials done to assess the effect of pirfenidone in IPF.

Aim

To evaluate whether pirfenidone reduces deterioration in lung function in IPF patients.

Patient Profile

Patients having a mean age of 40-80 years diagnosed with IPF over 48 months with no improvement in the disease.

Inclusion Criteria   

• Predicted FVC (forced vital capacity) of at least 50%
• Predicted carbon monoxide diffusing capacity (DL_CO) of at least 35%
• Either predicted FVC or predicted DL_CO of 90% or less
• 6 min walk test distance of at least 150 m
• Patients <50 years and not meeting the protocol criteria of IPF by high-resolution CT were required to have a lung biopsy sample showing usual interstitial pneumonia

Exclusion Criteria

• Obstructive airway disease
• Connective tissue disease
• Alternative explanation for interstitial lung disease
• Awaiting lung transplant

Method

Study Design

Multinational, double-blind, placebo-controlled phase-3 study.

Treatment Strategy

Study 004

Group 1 – n = 87 pirfenidone 1197 mg/day

Group 2 – n = 174 pirfenidone 2403 mg/day

Group 3 – n = 174 placebo

Study 006

Group 1 – n = 171 pirfenidone 2403 mg/day

Group 2 – n = 173 placebo

Primary End-point

• Change in percentage of predicted FVC from baseline to week 72

Secondary End-points

• Categorical FVC
• Progression-free survival
• Worsening IPF
• Dyspnea
• 6 min walk test (MWT) distance
• Worst peripheral oxygen saturation during 6 MWT
• Percentage predicted DL_CO
• Fibrosis by use of high resolution CT
• Overall deaths
• Deaths due to IPF

Results

• In study 004, mean FVC change at week 72 was -8% in pirfenidone group vs -12.4% in placebo
• In study 006, mean FVC change at week 72 was -9% in pirfenidone group vs -9.6% in placebo
• Categorical change in FVC >10% is shown in Figure 1

Adverse Events

• The incidence of adverse events was higher in the pirfenidone  group as compared to the placebo group
• Figure 2 shows the comparison in adverse events between the treatment and the control group

• The overall deaths were lower in the treatment group vs control (6% vs 8%)
• Deaths due to IPF were lower in the pirfenidone group vs control (3% vs 7%)

Conclusions

• Treatment with pirfenidone in IPF patients was associated with a better clinical outcome and a good safety profile.
• Pirfenidone represents a suitable treatment option in patients diagnosed with IPF.

Lancet 2011; 377: 1760–69