Biotechnology company aTyr Pharma announced topline results from its phase 3 EFZO-FIT study of efzofitimod for the treatment of adults with pulmonary sarcoidosis. The surprising news follows positive results from the 1b/2a phases of the trial in April.
Most notably, the developmental drug failed to meet its primary endpoint of change from baseline in mean daily corticosteroid (OCS) dose at week 48. Among the 268 patients in the study, those taking a dose of 5 mg/kg of efzofitimod reduced their steroid use to 2.79 mg a day from baseline. Patients who took a placebo reduced their steroid use to 3.52 mg a day — a difference that was not statistically significant and therefore did not meet the primary endpoint.
The study did demonstrate clinical improvement in the King’s Sarcoidosis Questionnaire (KSQ)-Lung score from baseline to week 48: a score of 10.36 for the 5 mg/kg efzofitimod cohort and 6.19 for the placebo cohort.
The proportion of patients who achieved complete steroid withdrawal with a stable KSQ-Lung score was 46.9% of patients on efzofitimod 5 mg/kg versus 35.7% of patients on placebo. Those who achieved complete steroid withdrawal and an improved KSQ-Lung score made up 29.5% of patients on efzofitimod 5 mg/kg versus 14.4% of patients on placebo. Lung function as measured by forced vital capacity (FVC) at week 48 was maintained.
Study participants in both the 3 mg/kg and 5 mg/kg dose groups generally well-tolerated the drug, which was consistent with observed safety profiles in previous phases of the trial.
Despite missing the primary endpoint, aTyr Pharma said efzofitimod demonstrated benefits across multiple clinically relevant efficacy endpoints and suggested it could be used as maintenance therapy that gets added to standard of care. The company said it plans to work with the U.S. Food and Drug Administration (FDA) to review the results and determine the appropriate path forward for efzofitimod in the treatment of pulmonary sarcoidosis.
“This study demonstrates that patients with chronic, symptomatic sarcoidosis can be managed with substantially lower steroid doses than previously thought. In spite of a higher than anticipated placebo response, we found that treatment with efzofitimod was associated with a greater amount of steroid reduction and an improvement in the KSQ-Lung score,” said Sanjay S. Shukla, MD, MS, president and CEO of aTyr Pharma, in a press release.
“The results of EFZO-FIT demonstrate not only strong evidence of clinical efficacy for efzofitimod’s effect on quality of life and its capacity to facilitate steroid withdrawal but also increased confidence that steroids overall can be reduced to manage symptoms and lung function without the fear of worsening disease,” said Daniel Culver, DO, principal investigator and chair of the department of pulmonary medicine at the Cleveland Clinic.
aTyr Pharma said it will present the results on September 30 at the European Respiratory Society Congress in Amsterdam.
