aTyr Pharma’s Phase 3 Efzofitimod Study Shows Clinical Activity Despite Missing Primary Endpoint In Pulmonary Sarcoidosis

aTyr Pharma, Inc., a clinical-stage biotechnology company developing novel medicines from its proprietary tRNA synthetase platform, announced topline results from the Phase 3 EFZO-FIT™ trial of efzofitimod in 268 patients with pulmonary sarcoidosis, a serious interstitial lung disease.

The study did not meet its primary endpoint of reducing the mean daily oral corticosteroid (OCS) dose at week 48. Patients on 5.0 mg/kg efzofitimod reduced to an average of 2.79 mg vs. 3.52 mg with placebo (p=0.3313). As the primary endpoint was not met, subsequent analyses are reported as nominal.

“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. 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-centre randomised controlled trial. The findings provide valuable insights about the treatment of pulmonary sarcoidosis, which are likely to inform treatment practices in the future,” said Daniel Culver, D.O., Chair of the Department of Pulmonary Medicine at the Cleveland Clinic and principal investigator of the trial. 

Despite this, efzofitimod demonstrated clinically meaningful signals of activity showing improved KSQ-Lung score at week 48 with 5.0 mg/kg (p=0.0479). Responder analysis showed more patients on 5.0 mg/kg achieved complete steroid withdrawal with improved KSQ-Lung scores compared to placebo (p=0.0199). Lung function (FVC) was maintained through 48 weeks.

“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. 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,” said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr Pharma. 

Dr. Shukla continued, “We are encouraged by the potential of efzofitimod to improve the lives of those living with sarcoidosis, and we are incredibly grateful to the patients, investigators, patient advocacy organizations and our partner Kyorin Pharmaceutical, Ltd., who all contributed to this important study.”

aTyr believes these findings support efzofitimod’s potential role in pulmonary sarcoidosis and plans to engage with the FDA to determine next steps for development. The EFZO-FIT™ study was a global, 48-week trial evaluating efzofitimod at 3.0 mg/kg and 5.0 mg/kg versus placebo, with an initial 12-week steroid taper protocol followed by continued taper or rescue as needed.