TJ Biopharma has announced the publication of results from PRIME-1, a phase 2 study of plonmarlimab in macrophage activation syndrome (MAS), in the Journal of Hematology & Oncology. Plonmarlimab is the company’s internally developed monoclonal antibody targeting GM-CSF.
PRIME-1 is an open-label, single-arm, multi-centre phase 2 study designed to evaluate the efficacy, safety, tolerability, pharmacokinetics and immunogenicity of plonmarlimab in patients with MAS. The findings showed encouraging clinical responses with a rapid onset of response and the potential to substantially reduce glucocorticoid use, providing further clinical evidence to support targeting GM-CSF in MAS.
MAS is a life-threatening hyperinflammatory condition that may arise as a complication of a range of autoimmune rheumatic diseases. Published reports from China indicate only approximately 40% of patients respond to first-line glucocorticoid therapy, while mortality in patients with relapsed or refractory MAS can exceed 60%. With no therapies currently approved specifically for MAS in China, substantial unmet medical needs remain.
The published study enrolled 18 patients with MAS who were refractory to or had relapsed after high-dose glucocorticoid therapy.
Key findings included: 83.3% overall response rate at Week 8: 15 of 18 patients achieved a complete or partial response, and the median time to respond was 2.1 weeks, although the earliest response was observed on Day 5 of treatment.
There was a 79.3% reduction in glucocorticoid dose. The least-squares mean percentage reduction from baseline was 79.3% at Week 8, with 83.3% of patients achieving a dose reduction of at least 50%.
The drug had a well-tolerated safety profile, the company said. No Grade 3 or higher infections were observed, and no adverse events led to permanent treatment discontinuation or death during the study.
“MAS can progress rapidly and become life-threatening, making prompt control of excessive inflammation critical,” said Zhao Wang of the Department of Hematology at Beijing Friendship Hospital, Capital Medical University, and a co-corresponding author of the publication.
“The encouraging and relatively rapid clinical responses observed in patients who had responded inadequately to prior treatment provide preliminary clinical evidence supporting the potential of GM-CSF-targeted therapy in MAS.”
“MAS is a serious complication of several autoimmune rheumatic diseases, and its treatment remains challenging,” said Qiong Fu of the Department of Rheumatology and Immunology at Renji Hospital, Shanghai Jiao Tong University School of Medicine, and a co-corresponding author of the publication.
“Alongside encouraging clinical responses, the study showed the potential for substantial reductions in glucocorticoid use. These findings warrant further investigation, and we look forward to their validation in subsequent studies.”
Plonmarlimab has received Breakthrough Therapy Designation from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for MAS. The publication of the phase 2 results and initiation of a phase 3 study mark continued progress in its clinical development. The Company is also conducting PRIME-2, a phase 2 study in gouty arthritis, and has received investigational new drug (IND) clearance to initiate PRIME-3, a phase 2 study in sepsis.
“Publication of these phase 2 results provides important support for the continued clinical development of plonmarlimab,” said Isaac Meng, chief medical officer of TJ Bio.
“We have initiated a phase 3 study in relapsed or refractory MAS associated with rheumatic diseases, alongside clinical development in additional indications. Through larger clinical studies, we aim to further establish the efficacy and safety of plonmarlimab and advance a potential new treatment option for patients with urgent unmet needs.”
The study also included analyses of inflammatory biomarkers. Levels of ferritin and interleukin-18 (IL-18) declined markedly during treatment, and changes in IL-18 were significantly correlated with changes in ferritin. The findings suggest IL-18 may have potential as a pharmacodynamic biomarker for assessing response to GM-CSF therapy.
“GM-CSF is a key upstream cytokine in inflammation, yet its therapeutic potential remains underexplored. Earlier development efforts largely focused on diseases driven by T cells,” said Xi Chen, chief scientific officer of TJ Bio.
“Our pioneering work on this pathway helped demonstrate the role of GM-CSF in aberrant macrophage activation. These phase 2 findings are consistent with our preclinical observations and strengthen the rationale for targeting GM-CSF in macrophage-driven inflammatory diseases, supporting further development of plonmarlimab across indications.”