Pulmonary sarcoidosis is a major form of interstitial lung disease or ILD, characterized by forming granulomas, clusters of inflammatory cells, in one or more body organs. Pulmonary sarcoidosis typically occurs in patients between 20 and 39 years of age. According to the American Lung Association, an estimated 200,000 Americans live with sarcoidosis, which may take benign or chronic forms and are asymptomatic, causing illness and death.

Oral corticosteroids continue to be the backbone of treatment for patients with pulmonary sarcoidosis, but harmful side effects and toxicity frequently accompany prolonged use. Lowering the steroid dose in these patients is challenging because doing so may worsen their symptoms and FVC. Therefore, significant therapeutic gaps continue to exist.

aTyr, working to develop a new class of drugs based on the extracellular biology of tRNA synthetase, Efzofitimod, presented a post-hoc analysis of the Phase Ib/IIa study in pulmonary sarcoidosis at the European Respiratory Society (ERS) at International conference taking place in Milan, Italy from September 9 to 13, 2023.

A first-in-class biologic immunomodulator called Efzofitimod is being tested in clinical settings to treat interstitial lung disease (ILD). It is a tRNA synthetase-derived treatment that targets inflammation without immunosuppression and selectively regulates activated myeloid cells through Neuropilin-2 to stop fibrosis progression.

In September 2021, aTyr Pharma announced positive results from a Phase Ib/IIa clinical trial of ATYR1923 in patients with pulmonary sarcoidosis. The trial found ATYR1923 to be safe and well-tolerated, with 33% of patients able to completely stop steroids and see improvements in forced vital capacity (FVC), cough, and fatigue. The trial met its primary endpoint, concluding that ATYR1923 was safe and well-tolerated. Efficacy was observed across primary endpoints, including a 58% reduction in steroid intake in the 5.0 mg/kg treatment group, with 33% of patients in the group able to discontinue steroids completely. Clinically significant improvements in forced vital capacity (FVC) of 3.3% and all measures of sarcoidosis symptoms, including dyspnea, cough, and fatigue, were observed.

These new data are from a post-hoc analysis, combining doses of Efzofitimod 3.0 and 5.0 mg/kg with placebo and Efzofitimod 1.0 mg/kg from the Phase Ib/IIa study of Efzofitimod in patients with pulmonary sarcoidosis, providing an indicator of treatment durability and effectiveness demonstrated in this study. Statistically significant differences in relapse rates after steroid dose reduction were observed in the two groups receiving the highest Efzofitimod dose, associated with significant improvements in FVC and quality of life measures, suggesting that Efzofitimod has the potential to become the first steroid-sparing and disease-modifying drug in the treatment for sarcoidosis.

The key findings from the study included:

• 7.7% of patients in the treatment group relapsed after steroid use, compared with 54.4% of patients in the placebo/under-treatment group;
• The rate of change in FVC was significantly improved in the treatment group compared with the placebo/under-treatment group;
• 52.9% of patients in the treatment group had an increase in KSQ-L ≥12 (three times the MCID) compared to 15.0% in the placebo/under-treatment group; and
• 64.7% of patients in the treatment group responded compared with 20.0% in the placebo/under-treatment group.

The company is investigating Efzofitimod in the global Phase III EFZO-FIT study in patients with pulmonary sarcoidosis. On the same lines, this ongoing study will provide crucial data about efzofitimod's potential in treating pulmonary sarcoidosis. ATYR1923 (Efzofitimod) was also granted ODD and FTD in 2022 by the US FDA to treat sarcoidosis.

With all things good, given the inherent risks and uncertainties in clinical trials, continuous monitoring of the ongoing clinical studies is a mandate that will provide crucial data about efzofitimod's potential in treating pulmonary sarcoidosis, determining its success rate in the future treatment scope.