FDA Grants Priority Review to Esbriet for Unclassifiable Interstitial Lung Disease

The U.S. Food and Drug Administration (FDA) has accepted and granted priority review to an application for Esbriet (pirfenidone) as a treatment for unclassifiable interstitial lung disease (UILD).

The supplemental new drug application was submitted by Genentech, Esbriet’s developer and a member of the Roche Group, based on positive results from a pivotal, 24-week Phase 2 trial (NCT03099187) in adults with UILD.

A decision on the approval is expected from the FDA by May of this year. Esbriet was approved in 2014 as an oral therapy to treat idiopathic pulmonary fibrosis in the U.S.

“Since its U.S. approval, Esbriet has become a standard of care for people living with idiopathic pulmonary fibrosis,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in a press release. “However, significant unmet need remains in fibrotic lung diseases, including unclassifiable interstitial lung disease. We are working closely with the FDA in hopes of offering Esbriet to people with UILD, a rare and debilitating disease.”

Interstitial lung diseases (ILD) are broad groups of more than 200 types of pulmonary diseases, including sarcoidosis and pulmonary fibrosis, and ILD associated with Sjögren’s syndrome and scleroderma. The disorders are diverse in their development, treatment, and progression but share some common features, such as coughing and shortness of breath.

Around 10% of individuals with ILDs are never given a definitive diagnosis and are therefore classified as having unclassifiable ILD. At present, no treatments are approved by the FDA to treat UILD.

The international Phase 2 trial, conducted at 70 centers worldwide, included 253 patients, ages 18 to 85, with unclassifiable ILD with signs of progressive lung dysfunction, including a predicted forced vital capacity (FVC) of at least 45%, a predicted carbon monoxide diffusing capacity of at least 30%, and more than 10% fibrosis as determined by high-resolution computed tomography scan.

The patients were randomly assigned to receive either Esbriet or a placebo for 24 weeks. Neither the participants nor the researchers knew who received the treatment and who received the placebo.

Esbriet treatment over 24 weeks was associated with a reduction in lung function decline, with the predicted median change in FVC being significantly lower in the Esbriet group (minus 87.7 mL) than in the placebo group (minus 157.1 mL), as measured by home spirometry. Moreover, the treatment was associated with a trend towards less loss of exercise capacity compared with placebo, as measured by the 6-minute walking distance test.

The most common treatment-related adverse events were gastrointestinal disorders, photosensitivity, and rash. All these are in agreement with the known safety profile of Esbriet in patients with pulmonary fibrosis.

Overall, results from the study, which was the first to assess Esbriet treatment specifically in patients with UILD, suggested that the therapy may be beneficial for this particular patient population.

In 2020, Esbriet was granted orphan drug designation and breakthrough therapy designation by the FDA as a potential treatment for UILD. These designations bring financial and regulatory incentives for the clinical development, approval, and commercial distribution of the treatment.