Roche’s Esbriet (Pirfenidone) Receives FDA Priority Review for Unclassifiable Interstitial Lung Disease (uILD)

January 26, 2021/Bio ValleyBIOON/--Roche recently announced that the U.S. Food and Drug Administration (FDA) has accepted a supplemental new drug application (sNDA) for Esbriet (pirfenidone) for the treatment of unclassifiable interstitial lung disease (UILD).FDAThe sNDA has been granted priority review, with an approval decision expected by May 2021.

In October 2014, Esbriet received U.S. FDA approval for the treatment of idiopathic pulmonary fibrosis (IPF). In 2020,FDAEsbriet was granted Orphan Drug Designation (ODD) and Breakthrough Therapy Designation (BTD) for the treatment of uILD.

Interstitial lung disease (ILD) is a rare, debilitating, and severe respiratory disease. Currently, there is noFDADrug Approved for the Treatment of Unclassifiable Interstitial Lung Disease (UILD). Phase IIClinical TrialData showed that at 24 weeks of treatment, Esbriet slowed disease progression in patients with uILD compared with placebo.

Levi Garraway, M.D., Chief Medical Officer and Global Head of Product Development at Roche, stated, “Since its approval in the United States, Esbriet has become a standard of care for patients with idiopathic pulmonary fibrosis (IPF). However, there remains a significant unmet need in fibrosing lung diseases, including uILD. We are working withFDA“Work closely together, hoping to provide Esbriet for UILD patients.”

Interstitial Lung Disease (Image source: welthi.com).jpg

ILD is a term that broadly describes more than 200 types of rare lung diseases. Although ILDs share similar features, including cough and shortness of breath, each type of ILD has distinct etiologies, treatments, and prognoses. Approximately 10% of ILD patients do not receive a definitive diagnosis even after thorough investigation and review by a multidisciplinary team.Diagnosis, in these cases, patients are classified as having UILD.

Esbriet’s New Indication Application for the Treatment of uILD, Based on a Phase IIClinical Trialdata. This is an international, multicenter, double-blind, randomized, placebo-controlled Phase II trial conducted at more than 70 clinical centers worldwide. The study enrolled adult patients (aged 18–85 years) with progressive fibrosing unclassifiable interstitial lung disease (UILD), who had a predicted forced vital capacity (FVC) ≥45%, a predicted diffusing capacity of the lung for carbon monoxide (DLco) ≥30%, and >10% fibrosis on high-resolution computed tomography (HRCT) over the past 12 months. The study evaluated the efficacy and safety of Esbriet versus placebo.

Notably, this trial represents the first randomized controlled trial specifically enrolling patients with progressive uILD. The results showed thatCompared with placebo, Esbriet significantly delayed disease progression and supported its efficacy on multiple pulmonary function parameters, including FVC.Specifically, within 24 weeks of treatment, as measured by home spirometry, the median change in predicted FVC in the Esbriet group was -87.7 mL (Q1–Q3: -338.1 to 148.6), compared with -157.1 mL (-370.9 to 70.1) in the placebo group. Within 24 weeks of treatment, as measured by site spirometry, the mean change in predicted FVC in the Esbriet group was lower than that in the placebo group (treatment difference: 95.3 mL, p=0.002). Results for DLco and the six-minute walk distance (6MWD) both favored Esbriet. In this trial, the safety and tolerability profile of Esbriet in patients with uILD was similar to that observed in Phase III trials in patients with idiopathic pulmonary fibrosis (IPF). The most common treatment-emergent adverse events (TEAEs) related to treatment were gastrointestinal disorders (47% in the Esbriet group vs. 26% in the placebo group), fatigue (13% vs. 10%), and rash (10% vs. 7%).

Compared with placebo, treatment with Esbriet was associated with less decline in lung function and exercise capacity. These results suggest that patients with progressive fibrosing uILD may benefit from treatment with Esbriet.

Esbriet is an oral medication approved for the treatment of idiopathic pulmonary fibrosis (IPF) and is available in multiple countries worldwide. Esbriet is an orphan drug; it was approved in Europe in 2011 for the treatment of adult patients with mild-to-moderate IPF, and in the United States in October 2014 for patients with IPF. In early 2017, the United StatesFDAApproved Esbriet 801 mg and 276 mg tablets as a new treatment option for IPF. The 801 mg tablet serves as a maintenance therapy option, reducing the daily pill burden for patients with IPF.

The exact mechanism of action of Esbriet is not fully understood, but it may involve interference with transforming growth factor-β (TGF-β) andTumorassociated with the production of tumor necrosis factor-alpha (TNF-α). TGF-β is a small-molecule protein involved in cell growth and the development of scarring (fibrosis), while TNF-α is a small-molecule protein involved in inflammation. In both 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 pulmonary fibrosis. Relevant clinical data demonstrate that Esbriet can slow the progression of IPF. Compared with placebo, treatment with Esbriet for 52 weeks significantly reduced the risk of death in IPF patients by 48% (p=0.01). At week 52 of treatment, the proportion of patients with a decline in predicted FVC from baseline of ≥10% was 17% in the Esbriet group versus 32% in the placebo group. Furthermore, compared with placebo, Esbriet significantly attenuated the decline in six-minute walk distance.

Idiopathic Pulmonary Fibrosis (IPF) is a rare lung disease that causes fatal, irreversible, and progressive scarring (fibrosis) of the lungs, leading to difficulty breathing and preventing the heart, muscles, and vital organs from receiving sufficient oxygen to function properly. The progression of IPF can be rapid or slow, but it ultimately results in debilitating stiffening and loss of lung function. It is estimated that there are approximately 100,000 IPF patients in the United States and around 110,000 in Europe. IPF is a disease more feared than cancer, with an unknown etiology and no cure. Currently, only a limited number of IPF patients undergo lung transplantation. IPF inevitably leads to shortness of breath and destroys healthy lung tissue. Approximately half of patients survive only three years after diagnosis, with a five-year survival rate of about 20%-30%. IPF typically occurs in individuals over the age of 45, with a higher prevalence in men than in women. (Bioon.com)

Original source:FDA grants priority review to Roche’s Esbriet (pirfenidone) for unclassifiable interstitial lung disease