Genentech, a member of the Roche Group, recently presented two abstracts on the company’s product Esbriet (pirfenidone), an oral drug developed for the treatment of pulmonary fibrosis (PF), at the American College of Chest Physicians Annual Meeting (CHEST 2015), held Oct. 24–28 in Montreal, Canada. Both abstracts were presented by Dr. Steven Nathan, Medical Director, Advanced Lung Disease and Transplant Program at Inova Fairfax Hospital.
Esbriet is an anti-fibrotic drug thought to act by decreasing the production of collagen, as well as growth and inflammatory factors, ultimately leading to a reduction in lung fibrosis. The drug has been shown in different Phase 3 clinical trials to be able to slow the decline of lung function in patients with idiopathic PF (IPF) and consequently disease progression. In October 2014, the U.S. Food and Drug Administration (FDA) approved Esbriet for IPF treatment, making it the first IPF drug to receive approval in the United States. Now, more than 10,000 people have received Esbriet.
Mortality is a key clinical outcome when assessing therapies for IPF treatment. All-cause mortality, referring to deaths caused by any reason, can represent a measure of a drug’s safety and efficacy. Researchers assessed the clinical impact of Esbriet treatment in all-cause mortality in IPF patients. In the presentation entitled “Effect of Pirfenidone on All-Cause Mortality in Patients with Idiopathic Pulmonary Fibrosis (IPF): Comparison of Pooled Analysis with Meta-Analysis from the ASCEND and CAPACITY Trials,” Dr. Nathan showed that Esbriet can reduce the risk of all-cause mortality over time in IPF patients enrolled in three different Phase 3 trials (ASCEND and two CAPACITY trials). The result was observed in three different time-points, at week 52 after the start of the treatment, week 72, and at the end of the study (120 weeks). In total, 1,247 IPF patients were analyzed.
Dr. Nathan showed that Esbriet, compared to a placebo, induced a 48% relative reduction in the risk of all-cause mortality at week 52, where 3.5% of the patients in the Esbriet group succumbed (22 out of 623) compared to 6.7% (42 out of 624) in the placebo group. A 37% relative reduction in the risk of death was observed 72 weeks after the start of the treatment (5.1% Esbriet group succumbed versus 8% placebo group), and 31% at week 120 (6.1% Esbriet group versus 8.7% placebo group).
On the second presentation, entitled “Effect of Pirfenidone on IPF-related Mortality Outcome Measures in Patients with Idiopathic Pulmonary Fibrosis (IPF): Pooled Data Analysis from the ASCEND and CAPACITY Trials,” Dr. Nathan revealed that Esbriet can reduce the risk, not only of all-cause mortality, but also of IPF-related mortality and treatment emergent IPF-related mortality over time.
Disease-related mortality is a widely used clinical outcome in studies to assess treatment benefits. This parameter is often seen as a supplement to all-cause mortality analysis, as deaths due to other causes rather than the condition being analyzed may mask findings in all-cause mortality. Researchers assessed IPF-related mortality and treatment emergent IPF-related mortality at weeks 52, 72 and 120 in a pooled IPF patients cohort of the ASCEND and CAPACITY Phase 3 trials.
Dr. Nathan reported that at week 52 into treatment, IPF-related mortality occurred in 1.6% of the patients under Esbriet treatment (10 out of 623) compared to 4.5% in the placebo group (28 out of 624 patients). As for the treatment emergent IPF-related mortality, the percentage of occurrence was also significantly lower in the Esbriet group (1.1%, 7 out of 623 patients) in comparison to the placebo group (3.5%, 22 out of 624 patients). A similar trend was also observed at week 72, where IPF-related death occurred in 2.7% of the patients under Esbriet treatment and 5.6% in the placebo group, with a treatment emergent IPF-related mortality of 1.8% in the Esbriet group and 4.5% in the placebo. At the end of the study (120 weeks), results were consistent with earlier time-points, with fewer patients in the Esbriet group succumbing from IPF (3.5%) and treatment-related causes (2.4%), in comparison to the placebo group (6.3% from IPF and 5.1% from treatment).
Overall, the findings demonstrated that Esbriet treatment can reduce the risk of all-cause mortality, and importantly also of IPF-related mortality and treatment emergent IPF-related mortality over time in IPF patients.
“We are encouraged that these data suggest Esbriet can reduce the risk of mortality for people with IPF and further emphasize the importance of early and continued treatment with the medicine. We are proud to help provide hope to people with this serious disease,” said Dr. Ben Kramer, vice president of Medical Affairs at Genentech, to Pulmonary Fibrosis News.
Pulmonary Fibrosis News, part of the BioNews Services group, had the opportunity to interview Dr. Nathan and Dr. Kramer on the findings reported at CHEST 2015 and future plans for Esbriet therapy. To read more on the interview, please visit the following link.