Efzofitimod Safe and Well Tolerated in Patients With Pulmonary Sarcoidosis

Treatment with efzofitimod (ATYR1923) appears to be safe and effective for patients with pulmonary sarcoidosis, according to clinical trial findings published in Chest.

Efzofitimod (ATYR1923), a novel immunomodulator that significantly reduced lung fibrosis and inflammation in preclinical studies, holds promise as a potential pulmonary sarcoidosis treatment that may have fewer side effects than corticosteroids (CS) and other existing treatments. A randomized, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT03824392) of efzofitimod for patients with pulmonary sarcoidosis explored the tolerability, safety, and effectiveness of this novel immunomodulator.

The investigators assessed the use of multiple ascending doses of efzofitimod administered intravenously every 4 weeks for 24 weeks in patients with pulmonary sarcoidosis. The study comprised 3 sequential dose cohorts with a 2:1 randomization (efzofitimod to placebo) in each of the cohorts. All participants underwent a CS taper to 5 mg/day by week 8 or to less than 5 mg/day after week 16. The participants were between 18 and 75 years of age, had a diagnosis of pulmonary sarcoidosis for at least 6 months, and had evidence of parenchymal involvement.

The primary study endpoint was evaluation of the safety and tolerability of efzofitimod vs placebo in patients with pulmonary sarcoidosis. Secondary endpoints included CS reduction, change in lung function, and patient-reported outcomes (PROs) in health-related quality-of-life scales. Exploratory outcomes assessed the change from baseline in lung function through week 24.

A total of 37 participants were randomly assigned to 4 study cohorts, with 12 patients receiving placebo, 8 receiving efzofitimod 1 mg/kg, 8 receiving efzofitimod 3 mg/kg, and 9 receiving efzofitimod 5 mg/kg. Of these individuals, 9 patients prematurely discontinued treatment, leaving a total of 28 participants who completed the study. The mean (SD) patient age was 52.4 (10.1) years; 54% were female.

Results of the study showed that efzofitimod was well tolerated at all doses, with no new or unexpected AEs and no dose-dependent AE incidence reported. The average daily CS doses through the end of the study were 7.2 mg in the placebo group vs 6.8 mg, 6.5 mg, and 5.6 mg in the 1-mg/kg, 3-mg/kg, and 5-mg/kg groups, respectively; these dosing levels were in turn associated with a baseline-adjusted relative CS reduction of 5%, 9%, and 22%, respectively.

Clinically meaningful improvements were attained across several PROs, with some of them reaching statistical significance in the 5-mg/kg dose arm. A dose-dependent trend toward improved lung function was also observed in the 3-mg/kg and 5-mg/kg groups, but it was not significant.

The key limitation of the present study was its small sample size; thus, the results will require confirmation in a larger study. Most of the study dropouts were attributable to operational site difficulties linked to the COVID-19 pandemic. The small sample size created baseline imbalances for several of the main endpoints and the confidence intervals were fairly wide, which limit the ability of the researchers to draw firm conclusions.

The authors concluded that “In patients with pulmonary sarcoidosis, efzofitimod was safe and well tolerated. Exploratory analyses suggest clinically meaningful improvements following 5 mg/kg efzofitimod on CS use and improvements in lung function and PROs compared to placebo, without increasing the risk of side effects.” The researchers also stressed that due to the limited number of study participants, results “should be considered only as hypothesis-generating.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.