Researchers at Genentech/Roche presented the outcomes of three studies investigating pirfenidone’s action in IPF patients, during the American Thoracic Society (ATS) 2016 International Conference, held in San Francisco, May 13-18.
Esbriet, also known by the generic name of pirfenidone, is an antifibrotic agent commonly prescribed as a treatment for mild to moderate cases of idiopathic pulmonary fibrosis (IPF). The drug has both an anti-inflammatory and anti-fibrotic action, key signaling pathways in IPF. Specifically, by reducing secretion and inhibition of TGF-β, and inflammatory mediators like TNF-α and IL-1β.
In the first study, entitled “Cardiovascular Events in 3 Trials of Pirfenidone in Idiopathic Pulmonary Fibrosis (IPF),” researchers investigated the occurrence of adverse cardiovascular and bleeding events in patients with IPF enrolled in three Phase 3 trials assessing pirfenidone, called the CAPACITY and ASCEND trials. The study included a total of 1,247 patients, where 623 patients received pirfenidone and 624 a placebo (control group). The trial results showed that both groups, pirfenidone and placebo control, had the same incidence for major adverse cardiac events or bleeding events, revealing that pirfenidone therapy does not induce an increased risk for cardiovascular or bleeding events in patients with IPF.
To further explore the benefits previously reported of continued treatment with pirfenidone in patients exhibiting a first decline of more than 10% in forced vital capacity (%FVC, a measure of lung function) in the first 6 months of therapy, researchers investigated patients’ subsequent outcomes following this period. The study, titled “Effect of Continued Treatment with Pirfenidone Following a ≥10% Relative Decline in Percent Predicted Forced Vital Capacity in Patients with Idiopathic Pulmonary Fibrosis (IPF)” suggested that continuing treatment with pirfenidone benefits patients’ outcomes, as it decreased the risk of %FVC decline or death during the subsequent 6 months.
Patients with IPF are frequently hospitalized. This is due to several reasons, including respiratory-related episodes, such as acute exacerbations of IPF, respiratory tract infections, respiratory failure, among other causes. Researchers investigated the proportion of patients from the three Phase 3 pirfenidone IPF trials that underwent hospitalization to understand if pirfenidone had any preventive effect. The team found that patients in the pirfenidone-treated group showed lower respiratory-related hospitalizations (7%), when compared to the placebo control group (12%), over 12 months. As The results suggested that treatment with pirfenidone may reduce the risk for respiratory-related hospitalizations. The findings were summarized in a study titled “Reduction in Non-Elective Respiratory-Related Hospitalizations in Patients Treated with Pirfenidone: Pooled Analyses from Three Phase 3 Trials of Pirfenidone in Idiopathic Pulmonary Fibrosis.”
In conclusion, the data presented at the ATS 2016 showed that pirfenidone treatment: i) does not increase the risk of cardiovascular or bleeding events over one year, compared to placebo; ii) may offer a potential benefit by slowing subsequent lung function decline, even among patients whose relative lung function declined by ≥10 percent within the first six months of treatment; and iii) may reduce the risk of non-elective respiratory-related hospitalizations.