Monoclonal Antibody Shows Promise for PSC Treatment

A new monoclonal antibody therapy has shown encouraging results for patients suffering from primary sclerosing cholangitis (PSC), a rare and progressive liver disease with no approved medical treatment. Researchers from the University of California, Davis have reported that the experimental drug nebokitug appears safe and potentially effective in reducing liver inflammation and fibrosis. The findings have been published in the American Journal of Gastroenterology.

Unmet Need in Primary Sclerosing Cholangitis

PSC is a chronic condition characterised by inflammation and scarring of the bile ducts, leading to bile accumulation and progressive liver damage. Over time, the disease can result in cirrhosis, liver failure and the need for transplantation. The cause of PSC remains unclear, though most patients also have inflammatory bowel disease, suggesting a gut–liver immune link. Current management is limited to symptom control and monitoring of complications, as no drug therapy has been proven to alter disease progression.

Mechanism and Rationale of Nebokitug

Nebokitug is a laboratory-engineered monoclonal antibody designed to block CCL24, a protein involved in inflammatory and fibrotic processes. In PSC patients, CCL24 levels are abnormally elevated and concentrated around bile ducts, where they promote immune cell activation and tissue scarring. Preclinical research has suggested that inhibiting CCL24 can reduce both inflammation and fibrosis, forming the scientific basis for testing nebokitug in human patients.

Phase 2 Trial Design and Safety Findings

The Phase 2 clinical trial enrolled 76 PSC patients across five countries. Participants were randomly assigned to receive one of two doses of nebokitug or a placebo via intravenous infusion every three weeks for a total duration of 15 weeks. The primary objective of the study was to assess safety and tolerability. Results showed that nebokitug was safe and well tolerated, with no significant safety concerns reported during the trial period.

Imporatnt Facts for Exams

• Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease.
• There is currently no approved drug therapy for PSC.
• Monoclonal antibodies are lab-made proteins targeting specific immune pathways.
• Phase 2 trials primarily assess safety and preliminary efficacy.

Early Signals of Efficacy and Clinical Implications

Beyond safety, patients receiving nebokitug, particularly those with more advanced liver scarring, showed improvements in liver stiffness and fibrosis-related biomarkers compared to placebo. According to Christopher Bowlus of UC Davis Health, the results suggest the therapy could meaningfully alter disease outcomes. While larger and longer trials are required, the study represents a significant step towards the first disease-modifying treatment for PSC, offering renewed hope to patients facing limited therapeutic options.