aTyr Pharma (Nasdaq: ATYR) announced topline results from its Phase 3 EFZO-FIT™ study of efzofitimod in pulmonary sarcoidosis. The study did not meet its primary endpoint of change in mean daily oral corticosteroid dose at week 48, with a reduction to 2.79 mg for efzofitimod vs 3.52 mg for placebo (p=0.3313).
However, notable secondary findings included: 52.6% of patients on 5.0 mg/kg efzofitimod achieved complete steroid withdrawal vs 40.2% on placebo, improved King’s Sarcoidosis Questionnaire-Lung scores (p=0.0479), and 29.5% of efzofitimod patients achieved both steroid withdrawal and lung score improvement vs 14.4% for placebo (p=0.0199). The drug was well-tolerated at both tested doses.
The company plans to engage with the FDA to determine the path forward for efzofitimod in pulmonary sarcoidosis treatment.
aTyr Pharma (Nasdaq: ATYR) ha annunciato i risultati principali dello studio di fase 3 EFZO-FIT™ di efzofitimod nella sarcoidosi polmonare. Lo studio non ha raggiunto l obiettivo primario di cambiamento della dose media giornaliera di corticosteroidi orali a 48 settimane, con una riduzione a 2,79 mg per efzofitimod contro 3,52 mg per placebo (p=0,3313).
Tuttavia, tra le conclusioni secondarie rilevanti: 52,6% dei pazienti trattati con efzofitimod 5,0 mg/kg hanno ottenuto l abolizione completa degli steroidi rispetto al 40,2% con placebo, punteggio migliorato nel King s Sarcoidosis Questionnaire-Lung (p=0,0479), e 29,5% dei pazienti efzofitimod hanno ottenuto sia l abolizione degli steroidi sia un miglioramento del punteggio polmonare rispetto al 14,4% del placebo (p=0,0199). Il farmaco è stato ben tollerato a entrambe le dosi testate.
La società intende confrontarsi con la FDA per determinare le prossime tappe per efzofitimod nel trattamento della sarcoidosi polmonare.
aTyr Pharma (Nasdaq: ATYR) anunció los resultados primarios de su estudio de fase 3 EFZO-FIT™ de efzofitimod en la sarcoidosis pulmonar. El estudio no alcanzó su objetivo primario de cambio en la dosis media diaria de corticosteroides orales a la semana 48, con una reducción a 2,79 mg para efzofitimod frente a 3,52 mg para placebo (p=0,3313).
Sin embargo, entre los hallazgos secundarios notables se incluyen: 52,6% de los pacientes en efzofitimod 5,0 mg/kg lograron la retirada completa de esteroides frente al 40,2% con placebo, mejoría en las puntuaciones del King s Sarcoidosis Questionnaire-Lung (p=0,0479), y 29,5% de pacientes con efzofitimod lograron tanto la retirada de esteroides como la mejora de la puntuación pulmonar frente al 14,4% de placebo (p=0,0199). El fármaco se toleró bien a ambas dosis probadas.
La compañía planea reunirse con la FDA para determinar el camino a seguir para efzofitimod en el tratamiento de la sarcoidosis pulmonar.
aTyr Pharma (나스닥: ATYR)는 efzofitimod의 폐 사르코이드증에 대한 제3상 EFZO-FIT™ 연구의 주요 결과를 발표했습니다. 연구는 48주차에 경구 코르티코스테로이드의 평균 일일 용량 변화의 주요 평가점을 충족하지 못했으며, efzofitimod의 감소량은 2.79 mg 대 위약 3.52 mg로 나타났습니다 (p=0.3313).
그러나 주목할 만한 보조 결과로는: 52.6%의 5.0 mg/kg 용량의 환자에서 완전 코르티코스테로이드 중단이 달성되었고 위약은 40.2%, King s Sarcoidosis Questionnaire-Lung 점수에서 개선(p=0.0479), 그리고 29.5%의 efzofitimod 환자에서 코르티코스테로이드 중단 및 폐 점수 개선이 함께 달성되었으며 위약은 14.4%(p=0.0199)였습니다. 두 용량 모두에서 약물은 잘 견디는 편이었습니다.
회사는 efzofitimod를 폐 사르코이드증 치료에 대해 향후 방향을 결정하기 위해 FDA와 협의할 계획입니다.
aTyr Pharma (Nasdaq: ATYR) a annoncé les résultats préliminaires de son étude de phase 3 EFZO-FIT™ sur l efzofitimod dans la sarcoïdose pulmonaire. L étude n a pas atteint son objectif principal de changement de la dose moyenne quotidienne de corticostéroïdes oraux à la semaine 48, avec une réduction à 2,79 mg pour efzofitimod contre 3,52 mg pour le placebo (p=0,3313).
Cependant, parmi les résultats secondaires notables: 52,6% des patients sous efzofitimod 5,0 mg/kg ont obtenu l arrêt complet des stéroïdes contre 40,2% sous placebo, amélioration des scores du King s Sarcoidosis Questionnaire-Lung (p=0,0479), et 29,5% des patients sous efzofitimod ont obtenu à la fois l arrêt des stéroïdes et une amélioration du score pulmonaire contre 14,4% pour le placebo (p=0,0199). Le médicament a été bien toléré aux deux doses testées.
La société prévoit de s entretenir avec la FDA afin de déterminer la voie à suivre pour efzofitimod dans le traitement de la sarcoïdose pulmonaire.
aTyr Pharma (Nasdaq: ATYR) gab die Endergebnisse der Phase-3-EFZO-FIT™-Studie von Efzofitimod bei der pulmonalen Sarkoidose bekannt. Die Studie erreichte keinen primären Endpunkt bezüglich der Veränderung der durchschnittlichen täglichen Dosis von oralen Kortikosteroiden in Woche 48, mit einer Reduktion auf 2,79 mg für Efzofitimod gegenüber 3,52 mg für Placebo (p=0,3313).
Zu den bemerkenswerten sekundären Ergebnissen gehören jedoch: 52,6% der Patienten unter Efzofitimod 5,0 mg/kg erreichten eine vollständige Ausschaltung von Steroiden gegenüber 40,2% unter Placebo, eine Verbesserung des King’s Sarcoidosis Questionnaire-Lung Scores (p=0,0479) und 29,5% der Efzofitimod-Patienten erreichten sowohl Steroidabsetzung als auch eine Verbesserung des Lungenwerts gegenüber 14,4% bei Placebo (p=0,0199). Das Medikament wurde bei beiden getesteten Dosen gut toleriert.
Das Unternehmen plant, mit der FDA über den weiteren Weg für Efzofitimod in der Behandlung der pulmonalen Sarkoidose zu sprechen.
aTyr Pharma (المدرجة في Nasdaq: ATYR) أعلنت عن النتائج النهائية لدراسة المرحلة الثالثة EFZO-FIT™ لدواء efzofitimod في الساركويد الرئوي. لم تتحقق النقطة الأساسية وهي التغير في المتوسط اليومي للجرعة الفموية من الكورتيكوستيرويدات في الأسبوع 48، مع انخفاض إلى 2.79 mg ل efzofitimod مقابل 3.52 mg للدواء الوهمي (p=0.3313).
مع ذلك، من النتائج الثانوية الملحوظة: 52.6% من المرضى الذين تلقوا efzofitimod بجرعة 5.0 mg/kg حققوا سحب كامل للكورتيكوستيرويدات مقارنة بـ 40.2% مع الدواء الوهمي، وتحسن في درجات King s Sarcoidosis Questionnaire-Lung (p=0.0479)، و29.5% من مرضى Efzofitimod حققوا سحب الستيرويدات وتحسنًا في الدرجة الرئوية مقارنة بـ 14.4% مع الدواء الوهمي (p=0.0199). الدواء تم تحمله بشكل جيد عند كلا الجرعتين المختبرتين.
الشركة تخطط للقاء مع الـ FDA لتحديد المسار المستقبلي لـ efzofitimod في علاج الساركويد الرئوي.
aTyr Pharma (纳斯达克股票代码：ATYR)宣布了其Phase 3 EFZO-FIT™ 研究中 efzofitimod 对肺部肉芽肿病的初步结果。该研究未达到其主要终点，即第48周日均口服糖皮质激素剂量的变化，efzofitimod 的下降至 2.79 mg，对照组为 3.52 mg（p=0.3313）。
然而，值得注意的次要发现包括：52.6% 的患者在 efzofitimod 5.0 mg/kg 组实现了完全停止使用类固醇，与安慰剂组的 40.2% 相比，King s Sarcoidosis Questionnaire-Lung 分数改善（p=0.0479），以及 29.5% 的 efzofitimod患者实现了类固醇停止和肺部评分改善两项均达到，而安慰剂为 14.4%（p=0.0199）。药物在两种剂量下均耐受良好。
公司计划与 FDA 会面，以确定 efzofitimod 在肺部肉芽肿病治疗中的前进路径。
Positive
- Clinical improvement in King’s Sarcoidosis Questionnaire-Lung score at week 48 (p=0.0479)
- Higher rate of complete steroid withdrawal (52.6% vs 40.2% for placebo)
- Significantly more patients achieved both steroid withdrawal and lung score improvement (29.5% vs 14.4%)
- Drug demonstrated consistent safety profile and was well-tolerated
- Lung function maintained as measured by forced vital capacity (FVC)
Negative
- Failed to meet primary endpoint of change in mean daily oral corticosteroid dose
- Higher than anticipated placebo response affected study results
- Statistical significance not achieved for several secondary endpoints due to hierarchical testing structure
Insights
aTyr’s Phase 3 study of efzofitimod missed its primary endpoint despite showing some promising secondary outcomes.
The Phase 3 EFZO-FIT™ trial results for efzofitimod represent a significant setback for aTyr Pharma. The study failed to meet its primary endpoint of change from baseline in mean daily oral corticosteroid dose at week 48, with the 5.0 mg/kg efzofitimod group showing a reduction to 2.79 mg versus 3.52 mg for placebo (p=0.3313) – not statistically significant. This is particularly disappointing as steroid reduction was the core goal of this therapy.
The trial design included a hierarchical statistical analysis plan, meaning that since the primary endpoint wasn’t met, all subsequent positive findings can only be considered nominal and not statistically confirmatory. While the company highlights some positive secondary outcomes – notably improvements in the King’s Sarcoidosis Questionnaire-Lung score (p=0.0479) and a higher proportion of patients achieving complete steroid withdrawal with KSQ-Lung improvement (29.5% vs 14.4%, p=0.0199) – these results cannot support regulatory approval without the primary endpoint success.
What’s particularly challenging here is the higher than anticipated placebo response (40.2% of placebo patients achieved complete steroid withdrawal), which likely contributed to the trial’s failure. This suggests either a strong placebo effect in sarcoidosis treatment or potential issues with the trial design and endpoints selected.
The
These results represent a significant commercial challenge for aTyr Pharma. Missing the primary endpoint in a Phase 3 study typically makes FDA approval unlikely without additional trials. While the company plans to engage with regulators, investors should recognize that the path forward will likely involve either:
- A completely new Phase 3 trial with different endpoints (costly and time-consuming)
- Attempting to convince the FDA that secondary endpoints justify approval (historically difficult)
- Pivoting development focus to other indications
The missed primary endpoint occurred despite some promising signals in secondary measures. The 52.6% complete steroid withdrawal rate in the treatment group versus 40.2% for placebo (p=0.0919) approached but didn’t reach statistical significance. Similarly, improvements in quality of life measures show biological activity but aren’t typically sufficient for approval.
What’s concerning from an investment perspective is the unexpectedly high placebo response, which undermined the trial’s ability to demonstrate clear efficacy. This could indicate fundamental challenges with the drug’s efficacy profile or issues with the selected endpoints.
The ongoing EFZO-CONNECT™ study in systemic sclerosis-related ILD now takes on heightened importance as a potential alternative pathway for the company. This represents aTyr’s best near-term opportunity to demonstrate clinical value for efzofitimod.
The market will likely view these results negatively despite management’s attempt to highlight positive secondary findings. The statement about “engaging with the FDA to determine the path forward” suggests significant uncertainty about the program’s future, which typically translates to increased investment risk.
Study did not meet primary endpoint in change from baseline in mean daily oral corticosteroid (OCS) dose at week 48, although clinical benefit for efzofitimod observed across multiple study parameters.
Clinical improvement in King’s Sarcoidosis Questionnaire (KSQ)-Lung score at week 48 observed in the 5.0 mg/kg efzofitimod treatment group vs placebo (p=0.0479).
Greater proportion of patients achieved complete steroid withdrawal at week 48 with a KSQ-Lung score improvement in the 5.0 mg/kg efzofitimod treatment group (
Efzofitimod was well-tolerated with a consistent safety profile.
Company plans to engage with the U.S. Food and Drug Administration (FDA) to determine the path forward for efzofitimod in pulmonary sarcoidosis.
Management to host conference call and webcast today at 8:30am ET / 5:30am PT.
SAN DIEGO, Sept. 15, 2025 (GLOBE NEWSWIRE) — aTyr Pharma, Inc. (Nasdaq: ATYR) (“aTyr” or the “Company”), a clinical stage biotechnology company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, today announced topline results from the Phase 3 EFZO-FIT™ study of efzofitimod in 268 patients with pulmonary sarcoidosis, a major form of interstitial lung disease.
The study did not meet its primary endpoint of change from baseline in mean daily oral corticosteroid (OCS) dose at week 48. The change from baseline in mean daily OCS dose reduced to an average of 2.79 mg for 5.0 mg/kg efzofitimod vs 3.52 mg for placebo (p=0.3313). The study’s statistical analysis plan was designed on a hierarchical assessment basis, as such since the primary endpoint was not met, all subsequent statistical testing is reported as nominal findings.
The study demonstrated a clinical improvement in the King’s Sarcoidosis Questionnaire (KSQ)-Lung score at week 48 for 5.0 mg/kg efzofitimod compared to placebo (p=0.0479), with a responder analysis of patients who achieved complete steroid withdrawal at week 48 with an improved KSQ-Lung score also showing improvement in patients treated with 5.0 mg/kg efzofitimod compared to placebo (p=0.0199). Lung function as measured by forced vital capacity (FVC) at week 48 was maintained.
Based on these findings, which we believe indicate drug activity for efzofitimod as evidenced by improvements across multiple clinically relevant efficacy endpoints, the Company plans to engage with the U.S. Food and Drug Administration (FDA) to review the results and determine the path forward for efzofitimod in 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, M.D., M.S., President and Chief Executive Officer of aTyr Pharma. “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.”
“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, D.O., Chair of the Department of Pulmonary Medicine at the Cleveland Clinic and principal investigator of the trial. “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.”
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.”
EFZO-FIT™ was a global Phase 3 interventional study in 268 patients with pulmonary 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, which included a protocol guided steroid taper in the first 12 weeks of the study, followed by continued taper or rescue until week 48.
Presented below are the families of endpoints analyzed in the study. As the primary endpoint did not achieve statistical significance, p-values for other endpoints are reported and should be interpreted as nominal p-values.
Study Outcome Measures at Week 48
- Steroid Reduction
- Primary Endpoint: Change from baseline in mean daily OCS dose to an average of 2.79 mg for 5.0 mg/kg efzofitimod vs 3.52 mg for placebo (p=0.3313)
- Complete steroid withdrawal achieved for
52.6% of patients treated with 5.0 mg/kg efzofitimod vs40.2% on placebo (p=0.0919)
- KSQ-Lung Score
- Change from baseline in KSQ-Lung score of 10.36 for 5.0 mg/kg efzofitimod vs 6.19 for placebo (p=0.0479)
- Proportion of patients who achieved complete steroid withdrawal with stable KSQ-Lung score was
46.9% of patients on 5.0 mg/kg of efzofitimod vs35.7% on placebo (p=0.1241) - Proportion of patients who achieved complete steroid withdrawal with KSQ-Lung improvement was
29.5% of patients on 5.0 mg/kg efzofitimod vs14.4% in placebo (p=0.0199)
- FVC
- Change from baseline in absolute percent predicted FVC of -1.81 for patients in the 5.0 mg/kg efzofitimod vs -2.11 in placebo (p=0.7875)
- Safety and Tolerability
- Generally well-tolerated at both the 3.0 mg/kg and 5.0 mg/kg doses, consistent with a previously observed safety profile in all trials conducted to date
The Company plans to present the EFZO-FIT™ topline results at the upcoming European Respiratory Society Congress on Tuesday, September 30, 2025, at 8:44am CEST in Amsterdam, Netherlands.
Conference Call and Webcast
aTyr will host a conference call and webcast to discuss the results today September 15 at 8:30am ET / 5:30am PT. Interested parties may access the call by registering here in order to obtain a dial in, personalized passcode and webcast information. Links to a live audio webcast and replay may be accessed on the aTyr website events page at: http://investors.atyrpharma.com/events-and-webcasts. An audio replay will be available for at least 90 days following the event.
About Pulmonary Sarcoidosis
Pulmonary sarcoidosis is an inflammatory disease characterized by the formulation of granulomas, clumps of inflammatory cells, in one or more organs of the body. Approximately 200,000 Americans live with pulmonary sarcoidosis and the prognosis ranges from benign and self-limiting to chronic, debilitating disease, permanent loss of lung function and death. Current treatment options include corticosteroids and other immunosuppressive therapies, which have limited efficacy and are associated with serious side-effects that many patients cannot tolerate long-term.
About Efzofitimod
Efzofitimod is a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease (ILD), a group of immune-mediated disorders that can cause inflammation and fibrosis, or scarring, of the lungs. Efzofitimod is a tRNA synthetase derived therapy that selectively modulates activated myeloid cells through neuropilin-2 to resolve inflammation without immune suppression and potentially prevent the progression of fibrosis. In addition to the global Phase 3 EFZO-FIT™ study of efzofitimod in patients with pulmonary sarcoidosis, a major form of ILD, efzofitimod is also being investigated in the Phase 2 EFZO-CONNECT™ study in patients with systemic sclerosis (SSc, or scleroderma)-related ILD. These forms of ILD have limited therapeutic options and there is a need for safer and more effective, disease-modifying treatments that improve outcomes.
About aTyr
aTyr is a clinical stage biotechnology company leveraging evolutionary intelligence to translate tRNA synthetase biology into new therapies for fibrosis and inflammation. tRNA synthetases are ancient, essential proteins that have evolved novel domains that regulate diverse pathways extracellularly in humans. aTyr’s discovery platform is focused on unlocking hidden therapeutic intervention points by uncovering signaling pathways driven by its proprietary library of domains derived from all 20 tRNA synthetases. aTyr’s lead therapeutic candidate is efzofitimod, a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease, a group of immune-mediated disorders that can cause inflammation and progressive fibrosis, or scarring, of the lungs. For more information, please visit www.atyrpharma.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are usually identified by the use of words such as “anticipate,” “believes,” “can,” “could,” “designed,” “expects,” “intends,” “may,” “plans,” “potential,” “upcoming,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by such safe harbor provisions for forward-looking statements and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements include, among others, statements regarding the potential therapeutic benefits and applications of efzofitimod; the potential for the results of EFZO-FIT™ to inform the treatment of pulmonary sarcoidosis in the future, including management of the disease with lower steroid doses; timelines and plans with respect to certain development activities (such as the timing of data from clinical trials); plans to engage the FDA to determine the path forward for efzofitimod in pulmonary sarcoidosis as well as our expectations with respect to the outcome of that meeting and next steps for the development of efzofitimod in pulmonary sarcoidosis; and certain development goals. These forward-looking statements also reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects, as reflected in or suggested by these forward-looking statements, are reasonable, we can give no assurance that the plans, intentions, expectations, strategies or prospects will be attained or achieved. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. Furthermore, actual results may differ materially from those described in these forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, uncertainty regarding geopolitical and macroeconomic events, risks associated with the discovery, development and regulation of efzofitimod, the risk that we or our partners may cease or delay preclinical or clinical development activities for efzofitimod for a variety of reasons (including difficulties or delays in patient enrollment in planned clinical trials), the possibility that existing collaborations could be terminated early, and the risk that we may not be able to raise the additional funding required for our business and product development plans, as well as those risks set forth in our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and in our other SEC filings. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
FAQ
What were the main results of aTyr Pharma’s Phase 3 EFZO-FIT trial for efzofitimod?
The trial missed its primary endpoint of steroid dose reduction, but showed positive secondary outcomes including 52.6% complete steroid withdrawal in the treatment group and improved lung scores versus placebo.
Did ATYR’s efzofitimod demonstrate safety in the Phase 3 sarcoidosis trial?
Yes, efzofitimod was well-tolerated at both 3.0 mg/kg and 5.0 mg/kg doses, showing a consistent safety profile with previous trials.
What percentage of patients achieved complete steroid withdrawal with lung improvement on efzofitimod?
29.5% of patients on 5.0 mg/kg efzofitimod achieved both complete steroid withdrawal and lung score improvement, compared to 14.4% on placebo (p=0.0199).
What is the next step for aTyr Pharma (ATYR) after the Phase 3 efzofitimod results?
aTyr plans to engage with the FDA to review the results and determine the path forward for efzofitimod in pulmonary sarcoidosis treatment.
How many patients participated in aTyr’s Phase 3 EFZO-FIT study?
The study included 268 patients with pulmonary sarcoidosis, making it the largest interventional study completed in sarcoidosis to date.
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