In 2017, the FDA approved pirfenidone and nintedanib based on clinical trials that showed the drugs slowed the progression of idiopathic pulmonary fibrosis. But the drugs’ mechanisms of action are unclear.

In the American Journal of Respiratory Cell and Molecular Biology article, Larissa Knüppel and colleagues report on their study of fibroblasts from IPF patients and healthy donors treated with the two drugs. They found that “both drugs act on important regulatory levels in collagen synthesis and processing.” Nintedanib, however, more effectively downregulated “profibrotic gene expression and collagen secretion.” The researchers also provide the first evidence that both drugs inhibit collagen I fibril formation. This discovery, they write, demonstrates “a completely novel mechanism of action for both drugs” and may represent a target for development of other IPF drugs.

The article is titled, "A Novel Antifibrotic Mechanism of Nintedanib and Pirfenidone: Inhibition of Collagen Fibril Assembly."