[13] Pirfenidone is frequently associated with gastrointestinal side effects such as dyspepsia, nausea, gastritis, gastroesophageal reflux disease and vomiting.
Patients are usually advised to avoid direct exposure to sunlight, including sun lamps, and to use protective clothing and sunscreening agents.
Dizziness typically resolves, although patients should know how they react to pirfenidone before undertaking activities that need mental alertness or coordination.
[15] A number of cell-based studies have shown that pirfenidone reduces fibroblast proliferation,[16][17][18][19] inhibits transforming growth factor beta stimulated collagen production[16][17][20][21][22] and reduces the production of fibrogenic mediators such as transforming growth factor beta.
[14] The drug was developed by several companies worldwide, including the original patent holder, Marnac,[26] InterMune (now part of Roche), Shionogi, and GNI Group.
The lawsuit asserts that Novartis subsidiary Sandoz did not apply for a license when it began to sell pirfenidone in the U.S. market.
Esbriet had a revenue of $740 million in the U.S. market (2021), and Genentech alleges that Sandoz's unlawful sale of pirfenidone has caused "significant financial harm.
"[27] In animal models, pirfenidone displays a systemic antifibrotic activity and has been shown to reduce biochemical and histopathological indices of fibrosis of the lung, liver, heart and kidney.
In this model, bleomycin administration results in oxidative stress and acute inflammation, with the subsequent onset of pulmonary fibrosis in a number of animal species including the mouse and hamster.
The antifibrotic effect of pirfenidone has been further established in animal models of cardiac (heart),[36][37][38] renal (kidney),[39][40] and hepatic (liver)[16][41][42] fibrosis, as well as in Dupuytren's contracture.
[46][47] The first Phase III clinical trial to evaluate the efficacy and safety of pirfenidone for the treatment of patients with idiopathic pulmonary fibrosis was conducted in Japan.
[46] Two randomized, double-blind, placebo-controlled Phase III studies in eleven countries across Europe, North America, and Australia.
[47] Patients with idiopathic pulmonary fibrosis were randomly assigned to treatment with oral pirfenidone or placebo for a minimum of 72 weeks.
They confirmed observations from previous clinical studies that pirfenidone significantly reduced the progression of idiopathic pulmonary fibrosis as measured by change in percent predicted forced vital capacity from baseline to week 52.
In addition, significant treatment effects were shown on both of the key secondary endpoints of six-minute walk test distance change and progression-free survival.
[49] Randomised studies comparing non-steroid drugs with placebo or steroids in adult patients with idiopathic pulmonary fibrosis were included.
In addition, meta-analysis of the two Japanese studies confirmed the beneficial effect of pirfenidone on the change in vital capacity from baseline compared with placebo.
[49] In May 2010, the U.S. Food and Drug Administration (FDA) declined to approve the use of pirfenidone for the treatment of idiopathic pulmonary fibrosis, requesting additional clinical trials.