Roche Esbriet (pirfenidone) Received Priority Review By The US FDA For The Treatment Of Unclassified Interstitial Lung Disease (uILD)!

- Feb 06, 2021-

Roche recently announced that the US Food and Drug Administration (FDA) has accepted a supplementary new drug application (sNDA) from Esbriet (pirfenidone) for the treatment of unclassified interstitial lung disease (UILD). The FDA has granted priority review to the sNDA and is expected to make an approval decision in May 2021.


In October 2014, Esbriet was approved by the US FDA for the treatment of idiopathic pulmonary fibrosis (IPF). In 2020, the FDA granted Esbriet the Orphan Drug Designation (ODD) and Breakthrough Drug Designation (BTD) for the treatment of UILD.


Interstitial lung disease (ILD) is a rare and debilitating severe respiratory disease. Currently, there are no drugs approved by the FDA for the treatment of unclassified ILD (UILD). Data from a phase II clinical trial showed that Esbriet slowed the progression of the disease in patients with UILD compared with placebo after 24 weeks of treatment.


Levi Garraway, MD, Chief Medical Officer and Global Product Development Director of Roche, said: "Since the US approval of listing, Esbriet has become a standard of care for patients with idiopathic pulmonary fibrosis (IPF). However, fibrotic lung diseases (including UILD) still has a lot of unmet needs. We are working closely with the FDA and hope to provide Esbriet to UILD patients."


ILD is a term that broadly describes more than 200 types of rare lung diseases. Although ILD has similar characteristics, including coughing and shortness of breath, each type of ILD has different causes, treatments, and prospects. Approximately 10% of ILD patients have been reviewed by a multidisciplinary team, and even after thorough investigation, a clear diagnosis cannot be obtained. In these cases, patients are classified as having UILD.


Esbriet's application for a new indication for the treatment of UILD is based on data from a phase II clinical trial. This is an international, multi-center, double-blind, randomized, placebo-controlled phase II trial carried out in more than 70 clinical centers around the world. The enrolled patients are adults with progressive fibrosis UILD (aged 18-85). These patients had predicted forced vital capacity (FVC) ≥45%, predicted carbon monoxide diffusion capacity (DLco) ≥30%, and high-resolution CT showed fibrosis ≥10% in the past 12 months. The study evaluated the efficacy and safety of Esbriet relative to placebo.


It is worth mentioning that this trial represents the first randomized controlled trial to specifically enroll patients with progressive UILD. The results showed that compared with placebo, Esbriet significantly delayed disease progression and supported its efficacy on multiple lung function parameters including FVC. Specifically, within 24 weeks of treatment, measured by a home spirometry, the median change in FVC predicted by the Esbriet group was -87.7 mL (Q1-Q3 -338.1 to 148.6), and the placebo group was -157.1 mL (- 370.9 to 70.1). Within 24 weeks of treatment, measured by site spirometry, the average change in FVC predicted by the Esbriet group was lower than that of the placebo group (treatment difference: 95.3 mL, p=0.002). DLco and six-minute walk (6MWD) test results are in favor of Esbriet. In this trial, the safety and tolerability of Esbriet in patients with UILD are similar to those observed in a phase III trial of patients with idiopathic pulmonary fibrosis (IPF), and the most common treatment-related adverse effects in the treatment process Events (TEAE) were gastrointestinal disease (47% in the Esbriet group and 26% in the placebo group), fatigue (13% vs 10%), and rash (10% vs 7%).


Compared with placebo, Esbriet treatment was associated with a smaller loss of lung function and exercise capacity. These results indicate that patients with progressive fibrosis and UILD may benefit from Esbriet treatment.


Esbriet is an oral drug that has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) and is available in many countries around the world. Esbriet is an orphan drug that was approved in Europe in 2011 for the treatment of adults with mild to moderate IPF and in October 2014 in the United States for IPF patients. In early 2017, the US FDA approved Esbriet 801mg and 276mg tablets as new options for IPF treatment. Among them, 801mg tablets can be used as a maintenance treatment option to reduce the daily number of drugs taken by patients with IPF.


The exact mechanism of Esbriet has not yet been completely eliminated, but it may be related to interference with the production of transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α). TGF-β is a small molecule protein involved in cell growth and scar (fibrosis) production, while TNF-α is a small molecule protein involved in inflammation. In the United States and the European Union, Esbriet has been granted orphan drug status for the treatment of IPF.


IPF is an irreversible, fatal, and progressive lung scar. Relevant clinical data show that Esbriet can slow down the progress of IPF. Compared with placebo, 52 weeks of Esbriet treatment significantly reduced the risk of death in IPF patients by 48% (p=0.01). The proportion of patients whose FVC was predicted to decrease from baseline by ≥10% at week 52 of treatment was 17% in the Esbriet treatment group and 32% in the placebo group. In addition, compared with placebo, Esbriet significantly reduced the decline in the 6-minute walk test distance.


Idiopathic pulmonary fibrosis (IPF) is a rare lung disease that can cause fatal, irreversible, and progressive scarring (fibrosis) of the lungs, causing breathing difficulties, as well as the heart, muscles and key organs Cannot get enough oxygen to work properly. The progress of IPF can be fast or slow, but it will eventually lead to hardening of the abolition and cessation of work. It is estimated that there are approximately 100,000 IPF patients in the United States and approximately 110,000 IPF patients in Europe. IPF is a more terrifying disease than cancer. Its cause is unknown and cannot be cured. Currently, only a limited number of IPF patients have received lung transplants. IPF will inevitably lead to shortness of breath and damage healthy lung tissue. After diagnosis, about half of the patients survive for only 3 years, and the 5-year survival rate is about 20%-30%. IPF usually occurs in people over 45 years of age, with more men than women.