21 January 2021 - - The US Food and Drug Administration has accepted the company's supplemental New Drug Application and granted Priority Review for Esbriet (pirfenidone) for the treatment of unclassifiable interstitial lung disease. The FDA is expected to make a decision on approval by May 2021, US-based biotechnology company Genentech said.

Genentech is a member of Switzerland's Roche Group (SIX: RO) (OTCQX: RHHBY).

The sNDA is based on results from a pivotal, 24-week Phase II trial, which was the first randomized controlled study specifically designed and conducted solely in people with UILD.

The data were presented as a late-breaking abstract at the 2019 European Respiratory Society's annual meeting and simultaneously published in The Lancet Respiratory Medicine.

In 2020, the FDA granted Orphan Drug Designation and Breakthrough Therapy Designation to Esbriet for UILD.

Interstitial lung disease broadly describes a diverse group of more than 200 types of rare pulmonary diseases. ILDs share similar features, including cough and shortness of breath.

However, each ILD has different causes, treatment approaches, and outlooks. Approximately 1 in 10 people living with ILD cannot be given a definitive diagnosis, even after a thorough investigation, and in these cases, they are categorized as having unclassifiable interstitial lung disease.

This international, multicenter, double-blind, randomized, placebo-controlled Phase II trial at 70 centers included patients (aged ≥18-85 years) with progressive fibrosing UILD, a percent predicted forced vital capacity of 45% or higher and percent predicted carbon monoxide diffusing capacity of 30% or higher, more than 10 % fibrosis on high-resolution CT, and a high-resolution CT from the previous 12 months.

The primary endpoint was mean change in FVC from baseline over 24 weeks, measured by daily home spirometry.

Key secondary endpoints included change in FVC measured by site spirometry; proportion of patients who had a more than 5% or more than 10% absolute or relative decline in percent predicted FVC measured by clinic-based spirometry; change in percent predicted DLco; change in six-minute walk distance; and several patient reported outcomes; all of which were compared with baseline.

The planned statistical model to estimate mean FVC decline could not be applied due to a number of physiologically implausible outlier results and short observation time for a few patients.

Over 24 weeks, predicted median change in FVC measured by home spirometry was -87.7 mL (Q1-Q3 -338.1 to 148.6) in the Esbriet group versus -157.1 mL (-370.9 to 70.1) in the placebo group.

Over 24 weeks, predicted mean change in FVC measured by site spirometry was lower in patients given Esbriet than placebo (treatment difference 95.3 mL, p=0.002).

Results for DLco and 6MWD generally trended in favor of Esbriet treatment. Adverse event reporting reflected the known safety profile of Esbriet in IPF.

The most common treatment-related and treatment-emergent adverse events in the Phase II UILD study were gastrointestinal disorders (47% in the Esbriet group vs. 26% in the placebo group), photosensitivity (8% vs. 2%), rash (10% vs. 7%), dizziness (8% vs. 3%), weight decreased (8% vs. 1%) and fatigue (13% vs. 10%). Esbriet treatment was associated with less loss of lung function and exercise capacity compared with placebo over 24 weeks.

The results of this study suggest that patients with UILD may benefit from Esbriet therapy.

Esbriet is an oral medicine approved for the treatment of idiopathic pulmonary fibrosis and is available in more than 60 countries worldwide. Esbriet was FDA-approved for use in people with IPF in October 2014.