Pimicotinib: A Promising New Hope for Chronic Graft-versus-Host Disease

The 66th ASH Annual Meeting, held in San Diego, California, from December 7-10, 2024, brought promising news for patients suffering from chronic Graft-versus-Host Disease (cGvHD). Abbisko Therapeutics, a Shanghai-based biopharmaceutical company, presented preliminary Phase 2 study results of pimicotinib (ABSK021), a novel, orally administered, highly selective, and potent small-molecule inhibitor of CSF-1R, in the treatment of cGvHD. The results demonstrated robust clinical efficacy and a well-tolerated safety profile, offering hope for a new therapeutic option in this challenging disease.

cGvHD is a leading cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation, with limited treatment options and significant unmet medical needs. The presentation highlighted the potential of pimicotinib in addressing this critical gap. In heavily pre-treated patients, pimicotinib achieved an overall response rate (ORR) of 64% across all affected organs, including the gastrointestinal tract, oral cavity, eyes, liver, joints and fascia, esophagus, skin, and lungs. Notably, the drug demonstrated improvements in pulmonary function tests, addressing a major challenge in cGvHD treatment.

Pimicotinib's mechanism of action as a CSF-1R inhibitor contributes to its long-term efficacy in treating cGvHD. By targeting colony-stimulating factor 1 receptor, which plays a critical role in macrophage signaling and fibrosis, pimicotinib helps alleviate symptoms and improve long-term outcomes in cGvHD patients. The drug's oral administration and robust clinical efficacy, as demonstrated by a 64% overall response rate (ORR) in heavily pre-treated patients, suggest its potential as a novel therapeutic option for managing cGvHD.

The preliminary data from the Phase 2 study showed that pimicotinib was generally well-tolerated, with most adverse events being Grade 1 and reversible. However, serum enzyme elevations were observed, predominantly grade 1, and characterized by a slowly accumulative increase before reaching stable. These elevations were not associated with liver or other end-organ injuries and typically required no intervention. The pattern of these elevations is consistent with other CSF-1R inhibitors, suggesting a liver macrophage-mediated clearance of these enzymes. Long-term monitoring is crucial to assess the clinical significance of these elevations and potential long-term side effects.



Pimicotinib's potential to reduce organ-specific symptom burden and improve pulmonary function tests in cGvHD patients could significantly enhance long-term quality of life. Preliminary data shows rapid and durable responses across inflammation- and fibrosis-dominated organs, accompanied by patient-reported symptom reductions. Specifically, lung response results indicate improvements in FEV1 and NIH Lung score, suggesting alleviation of shortness of breath. As cGvHD patients often face chronic symptoms and reduced lung function, pimicotinib's ability to address these issues could lead to improved long-term quality of life, potentially reducing the need for organ transplants or other invasive procedures.

In conclusion, pimicotinib's promising preliminary results in treating cGvHD offer hope for a new therapeutic option in this challenging disease. With an ORR of 64% and a well-tolerated safety profile, pimicotinib has the potential to improve organ-specific symptom burden and pulmonary function tests, enhancing long-term quality of life for cGvHD patients. However, further studies are needed to confirm these findings and assess potential long-term risks. As the drug continues to be evaluated in clinical trials, investors and healthcare providers alike should keep a close eye on its progress, as it may represent a significant advancement in the treatment of cGvHD.