Genentech Earns Priority Review for Lung Disease Drug Esbriet Following Positive Clinical Data

Genentech's Esbriet gains priority review. (Justin Sullivan/Getty Images) 

The U.S. Food and Drug Administration (FDA) has accepted Genentech’s supplemental New Drug Application (sNDA) and has granted Priority Review for the company’s unclassifiable interstitial lung disease (UILD) treatment Esbriet^® (pirfenidone). The FDA’s final decision on approval of the drug is expected by May 2021.

The recent sNDA accepted by the FDA was based on findings from a 24-week Phase II trial, the first randomized, placebo-controlled study to examine the effects of Esbriet in patients with UILD. Data from the trial were presented during a late-breaking abstract session at the 2019 European Respiratory Society’s annual meeting and were also published in The Lancet Respiratory Medicine.

In the multicenter trial, 253 patients with progressive fibrosing UILD were randomized to either 2403 mg Esbriet (n=127) or placebo (n=126). Participants also presented with a percent predicted forced vital capacity (FVC) of 45% or higher and percent predicted carbon monoxide diffusing capacity (DLco) of 30% or higher, a high-resolution computed tomography from the previous 12 months and more than 10% fibrosis on high-resolution CT.

Researchers used daily home spirometry to examine the mean change in FVC from baseline over a 24-week treatment period. Other endpoints in the study were the change in FVC, the proportion of patients who experienced a greater than 5% or more than 10% absolute or relative decline in percent-predicted FVC, change in percent predicted DLco, change in 6-minute walk distance (6MWD) as well as patient-reported outcomes.

The predicted median change in FVC over the 24-week period was -87.7 mL (Q1-Q3=-338.1-148.6) in patients randomized to pirfenidone versus -157.1 mL (-370.9-70.1) in patients randomized to placebo. The predicted mean change in FVC, as measured by site spirometry, was significantly lower in patients assigned to Esbriet (treatment difference=95.3 mL; p=0.002). Treatment with pirfenidone was associated with less loss of exercise capacity and lung function over the study period.

Additionally, the results for the 6MWD and DLco were “generally” in favor of Esbriet versus placebo. Common treatment-related and treatment-emergent adverse events included gastrointestinal disorders (47% for Esbriet vs. 26% for placebo), photosensitivity (8% vs. 2%), rash (10% vs. 7%), dizziness (8% vs. 3%), weight loss (8% vs. 1%) and fatigue (13% vs. 10%).

“Since its U.S. approval, Esbriet has become a standard of care for people living with idiopathic pulmonary fibrosis. However, significant unmet need remains in fibrotic lung diseases, including unclassifiable interstitial lung disease (UILD),” according to a statement made by Levi Garraway, M.D., Ph.D., Chief Medical Officer and head of Global Product Development at Roche. “We are working closely with the FDA in hopes of offering pirfenidone to people with UILD, a rare and debilitating disease.”

Esbriet was approved in October 2014 for the treatment of idiopathic pulmonary fibrosis (IPF). Currently, the therapy is available for IPF treatment in more than 60 countries. Pirfenidone was obtained by Genentech in 2014 when Roche acquired InterMune, a Brisbane, Calif.-based company that developed the therapy, under an $8.3 billion merger deal.

Last year, Esbriet also received Orphan Drug Designation and Breakthrough Therapy Designation for UILD. The sNDA for pirfenidone follows a legal battle, started in early 2019, that saw Genentech fighting to protect the drug from generic competition. Genentech went so far as filing 18 lawsuits over a few weeks to prevent other companies from selling their generic versions of the therapy for IPF.