Study identifies promising new treatment effective against rare liver disease - Video

A new experimental therapy may finally offer hope to patients living with primary sclerosing cholangitis (PSC)-a rare, chronic liver disease that has long lacked effective treatment options. Researchers from the University of California, Davis, report that a novel monoclonal antibody, called nebokitug, not only appears safe but also shows early signs of reducing inflammation and fibrosis in the liver.

The findings, published in the American Journal of Gastroenterology, are being hailed as a promising step forward for those who currently face liver transplantation as their only definitive option.

PSC is a progressive disease in which the bile ducts—tubes that carry bile from the liver to the intestine—become inflamed and scarred. Over time, this scarring narrows the ducts, causing bile to build up and injure the liver. Although its exact cause remains unclear, PSC is often linked with inflammatory bowel disease (IBD), suggesting that gut-liver inflammation plays a key role. Symptoms can range from fatigue and itchy skin to jaundice, and while medications help manage discomfort, none have been proven to slow or reverse liver damage.

Nebokitug is a lab-engineered antibody that targets a molecule called CCL24, a signaling protein known to drive inflammation and scar formation in the liver. By blocking CCL24, nebokitug aims to halt the chain reaction that damages bile ducts and leads to progressive fibrosis.

To test its safety and potential benefit, researchers conducted a phase 2 randomized, placebo-controlled trial across five countries, enrolling 76 PSC patients assigned to receive one of two nebokitug doses or a placebo intravenously every three weeks for 15 weeks. The study’s primary goal was to assess safety, while secondary analyses measured liver stiffness and biomarkers associated with fibrosis.

Results were encouraging: nebokitug was well-tolerated, with only mild injection-site discomfort reported and no serious side effects or hospitalizations. Notably, patients—especially those with more advanced scarring—showed marked improvements in liver stiffness and fibrosis markers compared with placebo.

Experts say larger, long-term trials are now needed to confirm how much clinical benefit the drug can deliver—but for the first time, patients with PSC may have a real candidate for an FDA approved therapy on the horizon.

REFERENCE: Ponsioen CY, Assis DN, Boberg KM, Bowlus CL, Deneau M, Thorburn D, Aabakken L, Färkkilä M, Petersen B, Rupp C, Hübscher SG; PSC Study Group. Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process. Gastroenterology. 2021 Dec;161(6):1764-1775.e5. doi:10.1053/j.gastro.2021.07.046. Epub 2021 Aug 10. PMID:34384749.