Positive results from four analyses based on clinical trials developed by Roche to evaluate the effectiveness of Esbriet (pirfenidone), an oral antifibrotic medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of idiopathic pulmonary fibrosis (IPF), were recently presented at this year’s European Respiratory Society (ERS) International Congress Sept. 3-7 in London.
Several authors analyzed the results obtained in the three Phase 3 trials: ASCEND (PIPF-016, 52 weeks, NCT01366209); CAPACITY (PIPF-004 and PIPF-006, 72 weeks, NCT00287716 and NCT00287729); and the RECAP trial (98 weeks; NCT00662038), an extension study that assessed the long-term safety of Esbriet in patients who had completed one of the previous trials. In these studies, IPF patients were given a daily dose of 2,403 mg of Esbriet or a matching dose of a placebo. Most patients received the established dose, but some patients did not respond well and were given a reduced Esbriet dose (see below).
The study, “Long-Term Safety Of Pirfenidone (PFD) In People With Idiopathic Pulmonary Fibrosis (IPF): Pooled Analysis Of 4 Clinical Trials,” was conducted by Paul Noble and his colleagues and evaluated the long-term safety of Esbriet in IPF patients.
In this analysis, researchers evaluated the safety outcomes from the first dose of Esbriet until 28 days after the last dose in 1,216 patients. The authors found that Esbriet treatment was interrupted in 45 percent of the patients due to adverse events related to the treatment, and that the most common side effects were IPF, skin irritation, and nausea, which was consistent with the known safety profile of the drug.
Another study, “Final Analysis Of RECAP, An Open-Label Extension Study Of Pirfenidone In People With Idiopathic Pulmonary Fibrosis (IPF),” conducted by Ulrich Costabel and his colleagues, assessed the safety of Esbriet provided by the results of the RECAP extension trial. Of the 1,334 patients who completed the previous trials, 1,058 entered the RECAP study and continued to be treated with Esbriet. The final results indicated that prolonged treatment with the drug had the same safety profile and adverse effects observed in the ASCEND and CAPACITY trials, with no new safety signals to be reported.
The analysis conducted by Steven Nathan and colleagues, titled “Dose Modifications And Dose Intensity During Treatment With Pirfenidone,” was aimed at understanding whether a dose reduction in Esbriet would still be effective in the treatment of IPF while keeping at bay gastrointestinal and skin-related side effects.
To do so, researchers analyzed the results from the CAPACITY and ASCEND trials, in which 424 patients received the whole dose and 199 patients were given a reduced dose. The effectiveness of Esbriet was evaluated by the rate of annual decline in forced vital capacity (FVC; a measure of lung function).
Results showed that patients on both the complete dose or reduced dose of Esbriet presented similar FVC results and improved in terms of disease progression. Also, side effects tended to occur earlier and with limited duration in patients who received the reduced dose of Esbriet.
The team concluded that dose adjustments can be made to reduce adverse symptoms triggered by Esbriet while still maintaining the drug’s effectiveness.
Finally, Mark Fisher and his colleagues conducted an analysis titled “Predicting Life Expectancy For Pirfenidone And Best Supportive Care (BSC) In Idiopathic Pulmonary Fibrosis (IPF),” to estimate the long-term survival of patients enrolled in the three clinical trials.
The authors calculated the survival rate by creating a statistical model that compared the outcomes of IPF patients who received BSC (best supportive care) and the results obtained in the trials. According to the team, the analysis suggests that Esbriet significantly improves life expectancy in people with IPF by nearly three years compared with BSC.
Taken together, the four analyses support the use of Esbriet as a safe and effective treatment to delay disease progression in IPF patients.