Genentech, a member of the Roche Group announced that the FDA has granted Breakthrough Therapy Designation to Esbriet® (pirfenidone) for adults with unclassifiable interstitial lung disease (uILD). The designation was granted based on data from a Phase II trial, which studied the efficacy and safety of Esbriet in uILD. The study represented the first randomized controlled trial to exclusively enroll patients with progressive fibrosing uILD.
“Today’s milestone for Esbriet builds on our continued commitment to improving the standard of care for people living with fibrotic lung diseases,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We look forward to discussing the data with the FDA with the hope of bringing our important medicine to those with uILD who are currently without a treatment option.”
ILD is a term that broadly describes a diverse group of more than 200 types of rare pulmonary diseases. While ILDs share similar features, including cough and shortness of breath, each ILD has different causes, treatment approaches, and outlooks. Approximately 10% of people living with ILD reviewed by a multidisciplinary team cannot be given a definitive diagnosis, even after a thorough investigation, and in these cases, people are categorized as having uILD.
The Phase II data supporting Breakthrough Therapy Designation were recently presented as a late-breaking abstract at the 2019 European Respiratory Society’s annual meeting and simultaneously published in The Lancet Respiratory Medicine. The data suggested Esbriet slowed disease progression and supported its efficacy on a number of lung function parameters including forced vital capacity (FVC), in people with uILD. The safety and tolerability profile of Esbriet in people with uILD was comparable with that observed in Phase III trials in people with idiopathic pulmonary fibrosis (IPF).
Breakthrough Therapy Designation is designed to accelerate the development and review of medicines intended to treat serious or life-threatening conditions with preliminary evidence that indicates they may demonstrate a substantial improvement over existing therapies. This is the 33rd Breakthrough Therapy Designation for Genentech’s portfolio of medicines.
About the Phase II Study
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 (FVC) of 45% or higher and percent predicted carbon monoxide diffusing capacity (DLco) 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 predicted change in FVC from baseline over 24 weeks, measured by daily home spirometry. Secondary endpoints were changed 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 6-min walk distance (6MWD), change in University of California San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) score, change in Leicester Cough Questionnaire score, change in cough visual analogue scale, and changes in total and subscores of the St. George’s Respiratory Questionnaire (SGRQ), all of which were compared with baseline.
Analysis of the primary endpoint was affected by intraindividual variability in home spirometry values, which prevented application of the prespecified statistical model to the primary endpoint assessment. 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 pirfenidone 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 pirfenidone than placebo (treatment difference 95.3 mL, p=0.002). Results for DLco and 6MWD generally trended in favor of pirfenidone treatment. Adverse event reporting reflected the known safety profile of pirfenidone. The most common treatment-related treatment-emergent adverse events were gastrointestinal disorders (47% in the pirfenidone group vs 26% in the placebo group), fatigue (13% vs 10%), and rash (10% vs 7%). Pirfenidone treatment was associated with less loss to lung function and exercise capacity compared with placebo over 24 weeks. The results of this study suggest that patients with progressive fibrosing uILD may benefit from pirfenidone therapy.