The FDA ( Food and Drug Administration ) has approved Esbriet ( Pirfenidone ) as a treatment for idiopathic pulmonary fibrosis ( IPF ) in the United States.
Idiopathic pulmonary fibrosis is a fatal disease caused by progressive scarring ( fibrosis ) of the lungs, which makes breathing difficult and prevents the heart, muscles and vital organs from receiving enough oxygen to work properly. The disease can advance quickly or slowly, but eventually the lungs will harden and stop working altogether.
The approval of Esbriet is based on data from a large, placebo-controlled phase III study known as ASCEND and is supported by two other large phase III trials known as CAPACITY 1 and 2.
In the ASCEND study, more patients who received Esbriet had a delay in the decline of lung function compared to those who received placebo as defined by the primary endpoint of percent change in forced vital capacity ( FVC ), a measure of how well the lungs work based on the amount of air one can exhale with force after inhaling as deeply as possible.
The most serious adverse events observed in people who received Esbriet compared to those who received placebo were: elevations in liver enzymes found in the blood ( a sign of liver damage; 3.7% vs 0.8% ), sensitivity to light or rash ( 9.0% vs 1.0% ) and gastrointestinal side effects that caused 2.2% of patients to discontinue treatment compared to 1.0% of those who received placebo.
Approximately 100,000 people in the United States have idiopathic pulmonary fibrosis, an irreversible and ultimately fatal disease characterized by progressive loss of the ability of the lungs to absorb oxygen due to scarring.
The cause is unknown and there is no cure.
Idiopathic pulmonary fibrosis inevitably causes shortness of breath and destruction of healthy lung tissue, although some people may experience periods of stability with the disease. The median survival time from diagnosis is two to five years, and the five-year survival rate is approximately 20 to 40%.
Idiopathic pulmonary fibrosis typically occurs in people over the age of 45, and tends to affect slightly more men than women.
The mechanism of action of Esbriet is not understood, although it is believed to interfere with the production of TGF-beta ( Transforming Growth Factor beta ), a small protein in the body involved in how cells grow and TNF alpha ( Tumor Necrosis Factor alpha ), a small protein that is involved in inflammation.
The FDA granted Esbriet Breakthrough Therapy Designation based on the positive data from the ASCEND clinical trial and the serious and life-threatening nature of idiopathic pulmonary fibrosis.
It has also been granted Orphan Drug designation in the United States.
The efficacy and safety profile of Esbriet was studied in one of the largest phase III programs to date in idiopathic pulmonary fibrosis and included three phase III studies.
The ASCEND study was a multinational, multicenter, randomized, double-blind, phase III study that enrolled 555 patients with mild to moderate idiopathic pulmonary fibrosis.
The primary endpoint was the percent change in FVC from baseline to the end of the study, measured at 52 weeks.
The study showed that after one year 17% of patients who received Esbriet had a decline in lung function ( measured by a decline in FVC of at least 10% ) compared to 32% of patients who received placebo.
The CAPACITY studies were two concurrent, multinational, multicenter, randomized, double-blind, phase III studies that enrolled collectively 779 patients with mild to moderate idiopathic pulmonary fibrosis.
The primary endpoint was the percent change in FVC from baseline to the end of the study, at 72 weeks.
Across the phase III trials of Esbriet, the most common adverse events ( observed in at least 10% of patients ) are nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, anorexia, gastro-esophageal reflux disease, sinusitis, insomnia, weight decrease and arthralgia. ( Xagena )
Source: InterMune, 2014