New therapies approved for idiopathic pulmonary fibrosis

FDA approved the first two drugs for the treatment of idiopathic pulmonary fibrosis (IPF) on the same day-October 15.

These new therapies for IPF are pirfenidone (Esbriet, Roche) and nintedanib (Ofev, Boehringer Ingelheim). Both drugs were granted fast track, priority review, orphan product, and breakthrough therapy designations by FDA, and have been approved ahead of their prescription drug user fee goal dates.

IPF, a progressive scarring (fibrosis) of the lungs, is an irreversible and fatal lung disease. It is estimated to affect approximately 128,000 persons in the United States, many of whom die from it in 3 to 5 years. Symptoms including shortness of breath and cough develop in most individuals with IPF between the ages of 50 and 70 years. IPF occurs slightly more frequently in men than women.

The new drugs pirfenidone and nintedanib are orally administered and will help slow the progression of IPF, that is, the decrease in lung function that IPF causes. The consequence of the affliction is breathing difficulties and oxygen deprivation to the heart, muscles, and vital organs that makes them unable to work correctly. With IPF, which can progress slowly or rapidly, the lungs ultimately stop working.

Pirfenidone is believed to block production of transforming growth factor (TGF)-beta and tumor necrosis factor (TNF)-alpha, per the manufacturer. TGF-beta is a small protein in the body involved in how cells grow, and TNF-alpha is another small protein involved with inflammation.

Nintedanib, a kinase inhibitor, works by blocking growth factor receptors that have been implicated in IPF, according to the manufacturer. These growth factor receptors include the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and the platelet-derived growth factor receptor (PDGFR).

FDA approvals for both drugs are based on data from clinical studies:

Nintedanib was approved due to findings from a phase 2 trial (TOMORROW) and two phase 3 trials (INPULSIS-1 and INPULSIS-2) including a total of 1231 patients. These trials compared 150 mg nintedanib twice daily with placebo for 52 weeks. A statistically significant reduction in the rate of decline of forced vital capacity (FVC; used to measure decline in lung function) was observed in all three studies for those patients receiving nintedanib.

Pirfenidone’s approval was based on data from a phase 3 study (ASCEND), which was then supported by two phase 3 studies (CAPACITY 1 and CAPACITY 2). More patients who received pirfenidone had a delay in lung function decline than did those who received a placebo. The total patients in all three studies was 1247. FVC was also used in these studies to measure decline in lung function.

Boehringer Ingelheim has announced that nintedanib will be available within 10 days of its date of FDA approval in the United States. Pirfenidone will be available within 2 weeks, according to Roche. Both companies have also put in place comprehensive patient support programs.

Until these drugs were made available, treatments for IPF have been limited to oxygen therapy, pulmonary rehabilitation, and lung transplantation. Neither drug has been tested against the other, nor in combination in the clinical trials that have been completed for both.

The California-based biotechnology company that developed pirfenidone, InterMune, was acquired by Roche at the end of September 2014.