Efzofitimod Fails to Meet Primary End Point in Phase 3 Pulmonary Sarcoidosis Trial

Efzofitimod did not significantly reduce the mean daily oral corticosteroid (OCS) dose after 48 weeks in people with pulmonary sarcoidosis although clinical benefits were observed. Accordingly, aTyr Pharma’s Phase 3 EFZO-FIT evaluating the therapy did not meet its primary endpoint.1

“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,” principal investigator Daniel Culver, DO, Chair of the Department of Pulmonary Medicine at the Cleveland Clinic, said in a statement.1 “This trial represents an important step forward for the field, as it is by far the largest interventional study completed in sarcoidosis to date, demonstrating the feasibility of conducting a global multi-center randomized controlled trial. The findings provide valuable insights about the treatment of pulmonary sarcoidosis, which are likely to inform treatment practices in the future.”

EFZO-FIT was a global interventional study sarcoidosis that compared the efficacy and safety of efzofitimod at 3.0 mg/kg and 5.0 mg/kg doses versus placebo after 48 weeks of treatment in 268 patients with pulmonary sarcoidosis. The trial protocol included a guided steroid taper in the first 12 weeks of the study, followed by continued taper or rescue until week 48.

Study investigators found that the 5.0 mg/kg efzofitimod group had a mean reduction to 2.79 mg in mean daily OCS dose compared to 3.52 in the placebo group (P = .3313). All further statistical testing is reported as nominal findings as the study’s statistical analysis plan was designed on a hierarchical assessment basis.1

Investigators did find a clinical improvement in the change from baseline on King’s Sarcoidosis Questionnaire (KSQ)-Lung score at week 48 for 5.0 mg/kg efzofitimod (10.36) compared to placebo (6.19; P = .0479). Furthermore, 46.9% of patients on 5.0 mg/kg of efzofitimod achieved complete steroid withdrawal with stable KSQ-Lung score compared to 35.7% on placebo (P = .1241).1

Furthermore, patients who achieved complete steroid withdrawal at week 48 with 5.0 mg/kg efzofitimod had greater improvements in KSQ-Lung compared to placebo (P = .0199). Overall, 52.6% of patients treated with 5.0 mg/kg efzofitimod achieved complete steroid withdrawal compared with 40.2% on placebo (P = .0919).1

Forced vital capacity (FVC) values at week 48 were maintained.The change from baseline in absolute percent predicted FVC was -1.81 for patients in the 5.0 mg/kg efzofitimod group compared to 2.11 in the placebo group (P = .7875).1

“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,” Sanjay S. Shukla, MD, MS, President and Chief Executive Officer of aTyr Pharma, added.1 “These consistent findings suggest that treatment with efzofitimod may positively impact quality of life and preserve lung function while reducing steroid burden, providing a meaningful benefit to patients. We look forward to discussing the totality of the data with the FDA in order to determine the path forward for efzofitimod in pulmonary sarcoidosis, as there remains an urgent need for a safe and effective treatment option to address the unmet needs of this underserved population.”

Efzofitimod was generally well-tolerated at both the 3.0 mg/kg and 5.0 mg/kg doses, with a safety profile consistent with that seen in other trials of the therapy. Further data on efzofitimod will be presented at the upcoming European Respiratory Society Congress on September 30, in Amsterdam, Netherlands. aTyr Pharma plans to engage with the United States Food and Drug Administration (FDA) to review the data and determine the path forward for efzofitimod in pulmonary sarcoidosis.

In June 2025, aTyr Pharma announced positive early data in people with diffuse and limited systemic sclerosis-related interstitial lung disease (SSc-ILD) from the ongoing Phase 2 EFZO-CONNECT study. Investigators found that all patients had stable or improved modified Rodnan Skin Score (mRSS) and 3 of 4 evaluable, efzofitimod-treated patients with diffuse SSc-ILD had at least a 4-point improvement.2

References

1. aTyr Pharma Announces Topline Results from Phase 3 EFZO-FIT™ Study of Efzofitimod in Pulmonary Sarcoidosis. News release. aTyr Pharma. September 15, 2025. https://finance.yahoo.com/news/atyr-pharma-announces-topline-results-113000869.html

2. Johnson V. Efzofitimod Shows Promising Early Efficacy in Systemic Sclerosis-Related Interstitial Lung Disease. Article. HCPLive. June 5, 2025. https://www.hcplive.com/view/efzofitimod-shows-promising-early-efficacy-in-systemic-sclerosis-related-interstitial-lung-disease