Efzofitimod for the Treatment of Pulmonary Sarcoidosis.

ABSTRACT

BACKGROUND: Pulmonary sarcoidosis is characterized by the accumulation of immune cells that form granulomas affecting the lungs. Efzofitimod (ATYR1923), a novel immunomodulator, selectively binds neuropilin 2, which is upregulated on immune cells in response to lung inflammation. RESEARCH QUESTION What is the tolerability, safety, and effect on outcomes of efzofitimod in pulmonary sarcoidosis? STUDY DESIGN AND METHODS: In this randomized, double-blind, placebo-controlled study evaluating multiple ascending doses of efzofitimod administered intravenously every 4 weeks for 24 weeks, randomized patients (21) underwent a steroid taper to 5 mg/d by week 8 or < 5 mg/d after week 16. The primary end point was the incidence of adverse events (AEs); secondary end points included steroid reduction, change in lung function, and patient-reported outcomes on health-related quality-of-life scales. RESULTS: Thirty-seven patients received at least one dose of study medication. Efzofitimod was well tolerated at all doses, with no new or unexpected AEs and no dose-dependent AE incidence. Average daily steroid doses through end of study were 6.8 mg, 6.5 mg, and 5.6 mg for the 1 mg/kg, 3 mg/kg, and 5 mg/kg groups compared with 7.2 mg for placebo, resulting in a baseline-adjusted relative steroid reduction of 5%, 9%, and 22%, respectively. Clinically meaningful improvements were achieved across several patient-reported outcomes, several of which reached statistical significance in the 5 mg/kg dose arm. A dose-dependent but nonsignificant trend toward improved lung function also was observed for 3 and 5 mg/kg. INTERPRETATION: Efzofitimod was safe and well tolerated and was associated with dose-dependent improvements of several clinically relevant end points compared with placebo. The results of this study support further evaluation of efzofitimod in pulmonary sarcoidosis. TRIAL REGISTRY ClinicalTrials.gov; No. NCT03824392; URL www. CLINICALTRIALS gov.