aTyr Pharma’s efzofitimod failed to meet the primary endpoint in the Phase 3 EFZO-FIT trial, while secondary findings inform its next study in pulmonary sarcoidosis.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
Results from the Phase 3 EFZO-FIT trial of efzofitimod in adults with pulmonary sarcoidosis were published online in The Lancet Respiratory Medicine on October 26, 2026. The study did not meet its primary endpoint of reducing mean daily oral corticosteroid (OCS) dose at week 48 compared with placebo, although selected secondary outcomes favoured the investigational therapy.
aTyr Pharma announced the publication on October 29, 2026. The findings highlight the difficulty of demonstrating a treatment-specific steroid-sparing effect in a trial in which substantial steroid reductions occurred across treatment groups.
Trial Design and Patient Population
EFZO-FIT (NCT05415137) was a global, multicentre, randomised, double-blind, placebo-controlled Phase 3 trial involving 268 adults with moderate to severe pulmonary sarcoidosis. Participants received intravenous efzofitimod at 3 mg/kg, efzofitimod at 5 mg/kg, or placebo every four weeks for 48 weeks.
The protocol included a 12-week corticosteroid taper beginning on day 15, with a target of complete withdrawal. Dose increases were permitted if sarcoidosis worsened. The efficacy and safety analyses included 264 participants: 90 in the placebo group, 86 receiving 3 mg/kg and 88 receiving 5 mg/kg.
Primary Endpoint Shows No Significant Steroid-Sparing Benefit
The placebo-adjusted change from baseline in mean daily OCS dose was 0.02 mg/day with efzofitimod 3 mg/kg (95% confidence interval [CI], −1.49 to 1.52; p=0.98) and −0.73 mg/day with 5 mg/kg (95% CI, −2.21 to 0.75; p=0.33).
Neither dose demonstrated a statistically significant advantage over placebo. Although mean daily OCS dose across the analysed population declined from 10.7 mg at baseline to 2.9 mg at week 48, this pooled reduction does not establish a treatment-specific effect.
The findings indicate that substantial steroid reduction was achievable under the trial’s management protocol, but EFZO-FIT did not establish that efzofitimod provided additional steroid-sparing benefit over placebo.
Secondary Outcomes and Lung Function
aTyr reported favourable findings across selected patient-reported outcomes, including the King’s Sarcoidosis Questionnaire (KSQ)-Lung score, Fatigue Assessment Scale, KSQ-General Health score, and complete steroid withdrawal accompanied by KSQ-Lung improvement.
The company’s September 2025 topline announcement reported a mean KSQ-Lung score change of 10.36 with efzofitimod 5 mg/kg versus 6.19 with placebo (nominal p=0.0479). Complete steroid withdrawal accompanied by KSQ-Lung improvement occurred in 29.5% and 14.4% of participants, respectively (nominal p=0.0199).
These findings warrant further investigation but are not confirmatory evidence of efficacy. Under the trial’s hierarchical testing plan, failure of the primary endpoint meant that subsequent p-values were nominal.
For lung function, the earlier topline analysis reported changes in percentage-predicted forced vital capacity (FVC) of −1.81 with efzofitimod 5 mg/kg and −2.11 with placebo (p=0.7875). This comparison did not demonstrate a statistically significant difference between groups.
Safety Findings
Most adverse events were grade 1 or 2, and serious treatment-emergent adverse events occurred at similar rates across the groups.
Headache was reported in 19% of participants receiving efzofitimod 5 mg/kg, 13% receiving 3 mg/kg and 4% receiving placebo. Sinusitis occurred in 10%, 7% and 2%, respectively. Two participants receiving efzofitimod 3 mg/kg died, one from respiratory failure and the other following incarceration of a pre-existing inguinal hernia. Neither death was considered treatment-related.
These observations describe events during the trial and do not establish long-term safety or a favourable benefit-risk profile.
Revised Phase 3 Strategy
On September 24, 2026, aTyr announced alignment with the US Food and Drug Administration (FDA) on a new global Phase 3 protocol targeting patients with chronic, symptomatic pulmonary sarcoidosis and restrictive lung disease.
The planned study is expected to enrol up to approximately 372 patients and evaluate efzofitimod 5 mg/kg or placebo intravenously every three weeks over a 54-week study period. The primary endpoint will be change from baseline in FVC at week 48, with KSQ-Lung score change as the key secondary endpoint. Background corticosteroid and immunosuppressant treatment will remain stable.
The revised design reflects a shift from steroid reduction in a broader population towards lung function in a more narrowly defined group. aTyr cited subgroup findings from EFZO-FIT to support this approach. However, those findings do not establish that the new trial will succeed, and the proposed study remains subject to further development and funding requirements.
Clinical Interpretation
EFZO-FIT did not demonstrate a statistically significant steroid-sparing benefit for efzofitimod over placebo. Selected patient-reported outcomes provide a rationale for continued investigation, but their nominal statistical status limits the conclusions that can be drawn from them.
The next Phase 3 study will test whether efzofitimod can demonstrate a treatment effect on lung function in patients with restrictive lung disease. Until those results are available, the clinical benefit of efzofitimod in pulmonary sarcoidosis remains unconfirmed.
References
aTyr Pharma. aTyr Pharma Announces Publication of Results from the Phase 3 EFZO-FIT Study of Efzofitimod in Pulmonary Sarcoidosis in The Lancet Respiratory Medicine. 29 October 2026.
Culver DA, et al. Efzofitimod versus placebo in patients with pulmonary sarcoidosis (EFZO-FIT): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(26)00283-3/abstract
aTyr Pharma. aTyr Pharma Announces Topline Results from Phase 3 EFZO-FIT Study of Efzofitimod in Pulmonary Sarcoidosis. September 15, 2025.
ClinicalTrials.gov. Efficacy and Safety of Intravenous Efzofitimod in Patients with Pulmonary Sarcoidosis. NCT05415137.
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.