According to a study recently published in the European Respiratory Journal (ERJ)
, Pirfenidone has shown clinical benefit in patients with idiopathic pulmonary fibrosis (IPF), decreasing 24-hour cough by 34% in 74% of all patients enrolled.
The underlying cause of IPF has yet to be identified, but the disease can progress quickly if not treated properly. Common symptoms in patients include shortness of breath, fatigue, dry, hacking cough, and shallow breathing. Until the 2014 approvals of Ofev (nintedinib) and the antifibrotic and anti-inflammatory agent Esbriet (pirfenidone), standard-of-care was limited to oxygen therapy, pulmonary rehabilitation, and/or lung transplant.
Rare Disease Report
spoke with pulmonologist Dr. Marlies S. Wijsenbeek, Department of Respiratory Medicine, Erasmus University Medical Center (Rotterdam The Netherlands), one of the study's lead authors, about the newly-published data.
What is the mechanism of action in pirfenidone and what is its target?
Pirfenidone is thought to have pleiotrophic effects, but the exact mechanism of action is not known.
What challenges have been had historically as it pertains to treating IPF patients?
IPF is a progressive, deadly disease with a poor prognosis. The disease course varies by patient and is often unpredictable. Furthermore, many patients experience a high symptom burden, with dyspnea, cough and fatigue having the greatest impact on their lives. The only cure for IPF is lung transplantation, which is only possible in a small percentage of patients.
Until October 2014, there were no FDA-approved medicines for the approximately 100,000 people in the U.S. living with this irreversible lung disease. Fortunately, there are now two approved medicines (pirfenidone and nintedanib) that slow the progression of the disease.
: Were there any surprising conclusions made from the study? Was it expected to perform as successfully as it did?
: The objectives of this study were to objectively measure the effect of pirfenidone on cough in patients with IPF suffering from substantial cough and to assess the effect of pirfenidone on subjective cough and quality of life (QoL) measures. The study was conducted in an international collaboration in 4 centers in the Netherlands, Italy, France and the UK. Of the 46 patients screened for the study, 43 patients were included. Thirty-eight patients completed 4 weeks of the study, and 31 completed 12 weeks. We found that at 12 weeks, pirfenidone reduced the objective cough counts on average by 34%. This change was meaningful to patients and also had a positive effect on their cough-related QoL.
The idea for the study came from observations in the clinic that patients reported coughing less once starting pirfenidone, so the fact that we have now objectively measured and confirmed this was not so unexpected. What was an eye-opener to me is the incredible amount of times patients coughed - some more than 3000 times per day. Just imagine what that does to you and the people around you.
What adverse events were experienced by patients dosed with pirfenidone?
Fatigue (23%), loss of appetite (19%), and nausea (16%) were the most frequently reported adverse events. Two patients had a Serious Adverse Event, considered unrelated to the use of pirfenidone. The adverse events we observed are in line with the clinical experiences we have and that are reported for pirfenidone.
What are the next steps to be taken as it pertains to pirfenidone as a potential therapy for IPF patients?
The effect of pirfenidone was studied in three large Phase III trials in which pirfenidone was shown to slow lung function decline, as demonstrated by a lung function measure called forced vital capacity (FVC). Pre-specified post-hoc analysis also showed an effect on survival. I think in the current era, research pertaining to pirfenidone in IPF, is focused on combining existing or new drugs with pirfenidone, with the ultimate goal of halting disease progression or even reversing fibrosis.
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