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 (2:1) 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.

Keywords: ATYR1923; corticosteroids; efzofitimod; fatigue assessment scale; immunomodulator; lung function; neuropilin 2; pulmonary sarcoidosis; quality of life; steroid taper.

Graphical abstract

Figure 1

Flow diagram showing patient disposition (Modified Intention-to-Treat Population). ^aSite closures related to the COVID-19 pandemic. AE = adverse event.

Figure 2

A, B, Line graphs showing change from baseline lung function in the efzofitimod vs the placebo groups (modified intention-to-treat population): absolute FVC % predicted (A) and absolute change from baseline in FVC % predicted (B) from day 1 to the end of study.