Pirfenidone: A Recently Approved Option for Patients With IPF

A symposium on idiopathic pulmonary fibrosis (IPF), which was presented on behalf of InterMune, Inc, highlighted clinical data supporting the use of pirfenidone in patients with IPF. Leading the panel discussion was Steven Nathan, MD, FCCP, a principal investigator involved in studies of pirfenidone. Dr Nathan was joined by IPF experts Lisa Lancaster, MD, of Vanderbilt University Medical Center and Marilyn Glassberg, MD, of the University of Miami Health System.

The efficacy and safety of pirfenidone were evaluated in the CAPACITY 004 and 006 studies; one study had positive results and the other had negative results. Although an FDA panel initially voted 11 to 3 in favor of approval of pirfenidone based on the data from the CAPACITY studies, the FDA decided not to approve the drug and requested a third study. The results of the phase 3 ASCEND study demonstrated the efficacy of pirfenidone.¹ Pirfenidone received FDA approval on October 15, 2014.

IPF is thought to be a disease of dysregulated wound healing in the lungs that leads to progressive fibrosis and pulmonary decline. The clinical progression of IPF is unpredictable. Some patients experience years of gradual decline followed by a precipitous drop in lung function, whereas others may experience a stepwise decline. Physicians diagnose approximately 15,000 to 20,000 new cases of IPF yearly in the United States. The diagnosis of IPF is clinically challenging, as it is a diagnosis of exclusion; high-resolution CT scanning and lung biopsy may aid in diagnosis. The accuracy of diagnosis is optimized by a multidisciplinary approach.^2,3

Dr Glassberg discussed the results of the CAPACITY studies and the ASCEND phase 3 study. In all studies, patients with IPF were required to have a forced vital capacity (FVC) of 50% or greater at baseline. The baseline diffusing capacity in the lung for carbon monoxide of enrolled patients was 30% or greater (in ASCEND) and 35% or greater in both CAPACITY studies. The CAPACITY studies were conducted over the course of 72 weeks, with data collected for some patients for up to 120 weeks of treatment, whereas ASCEND was a 52-week study.¹

In the ASCEND study, 555 patients were randomized to receive 2403 mg of pirfenidone daily or placebo for 52 weeks. The percentage of patients with a 10% or greater decline in FVC over the study period was significantly lower in the pirfenidone group versus the placebo group (relative risk reduction 47.9%; P <.001).¹

In terms of reductions in FVC at week 52, 10% of placebo-treated patients in the 2 CAPACITY studies and the ASCEND study versus 23% of pirfenidone-treated patients had zero change or an improvement in FVC. Conversely, a total of 32% of patients taking placebo versus 17% of patients taking pirfenidone experienced a 10% or greater decline in FVC. Treatment with pirfenidone more than doubled the number of patients experiencing no change or an improvement in FVC over 52 weeks, and nearly halved the number of patients with a 10% or greater FVC decline over the same period. These results showed that pirfenidone reduced disease progression based on lung function measures.¹

Following Dr Glassberg’s description of the efficacy data, Dr Lancaster described some of the characteristics of pirfenidone, including dosing information.

Before initiation of pirfenidone, and periodically throughout treatment, patients should undergo liver enzyme testing. Each capsule contains 267 mg of pirfenidone. The initial dosage is 1 capsule 3 times daily with food for the first week, followed by 2 capsules 2 times daily with food for the second week. Thereafter, treatment is continued at the maintenance dose of 3 capsules 3 times daily with food.

In studies, 9% of patients taking pirfenidone versus 1% of patients taking placebo experienced photosensitivity reactions. Patients taking pirfenidone should be aware of the potential for photosensitivity with use of the medication, and should use proper sun protection.

In some cases, pirfenidone use has been associated with increases in liver enzyme levels, although to date, these increases have been reversible upon discontinuation of the medication.

Gastrointestinal adverse events requiring dosage reduction occurred in 18.5% of patients taking pirfenidone versus 5.8% of patients taking placebo. The adverse events that were most commonly associated with dosage reduction were nausea, diarrhea, vomiting, and dyspepsia. In clinical studies, discontinuation of pirfenidone was uncommon. Across the 3 clinical studies, over 80% of patients completed study treatment.

REFERENCES

1. King TE Jr, Bradford WZ, Castro-Bernardini S, et al; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083-2092.
2. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788-824.
3. American Thoracic Society; European Respiratory Society. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med. 2002;165(2):277-304.