New Monoclonal Antibody Shows Promise for Rare Liver Disease

A potential breakthrough has emerged for patients suffering from primary sclerosing cholangitis (PSC), a rare and chronic liver disease with limited treatment options. Researchers from the University of California–Davis have reported promising results from a Phase 2 clinical trial of a monoclonal antibody therapy called nebokitug.

The findings, published in the American Journal of Gastroenterology, suggest that nebokitug is safe and may reduce liver inflammation and scarring. For PSC patients, this development brings renewed hope, as no effective drug therapy currently exists beyond liver transplantation.

What Is Primary Sclerosing Cholangitis?

PSC is a long-term liver condition that causes inflammation and scarring of the bile ducts. These ducts transport bile from the liver to the small intestine, where it helps digest fats.

When bile ducts narrow or become blocked, bile builds up inside the liver. Over time, this process leads to liver damage, fibrosis, and eventually liver failure. Many PSC patients also face a higher risk of infections, cirrhosis, and bile duct cancer.

Doctors still do not fully understand what causes PSC. However, most patients also suffer from inflammatory bowel disease, particularly ulcerative colitis. This strong overlap suggests a link between gut inflammation and liver injury.

Limited Treatment Options Until Now

PSC has no cure. Current treatment strategies focus on managing symptoms and complications rather than slowing disease progression. Patients often experience fatigue, intense itching, and jaundice, although some remain symptom-free in early stages.

As the disease advances, many patients ultimately require a liver transplant. This reality has driven an urgent search for therapies that can delay or prevent liver failure.

How Nebokitug Works

Nebokitug is a laboratory-engineered monoclonal antibody designed to block CCL24, a protein involved in inflammation and tissue scarring.

Researchers have found that CCL24 levels increase significantly in PSC patients. The protein concentrates around bile ducts, where it attracts inflammatory cells and promotes fibrosis. By blocking CCL24, nebokitug aims to interrupt this damaging cycle.

Previous studies suggested that suppressing CCL24 could reduce inflammation and slow fibrosis, making it a strong therapeutic target.

Details of the Phase 2 Trial

The Phase 2 clinical trial enrolled 76 PSC patients across five countries. Researchers randomly assigned participants to receive either nebokitug at one of two doses or a placebo.

Patients received intravenous infusions every three weeks for a total of 15 weeks. The primary goal of the trial focused on safety and tolerability rather than definitive effectiveness.

According to the research team, nebokitug met the safety goal. Patients tolerated the treatment well, with no major safety concerns reported.

Encouraging Signs of Effectiveness

While safety remained the main objective, researchers also observed encouraging signals of benefit. Patients who received nebokitug, particularly those with more advanced liver scarring, showed improvements in key clinical markers.

These included reductions in liver stiffness and favorable changes in fibrosis-related biomarkers when compared with the placebo group. Such changes suggest that the drug may slow disease progression.

Dr. Christopher Bowlus, chief of Gastroenterology and Hepatology at UC Davis Health, said the results could be life-changing for PSC patients. He noted that reducing inflammation and fibrosis should translate into better long-term outcomes.

A Step Toward an Approved Therapy

Experts caution that further studies are needed before nebokitug can receive regulatory approval. Larger and longer trials must confirm whether the treatment improves survival and delays the need for liver transplantation.

Still, specialists describe the findings as a major step forward. For a disease that has seen decades of failed drug trials, nebokitug represents one of the most promising candidates to date.

If future studies confirm these results, nebokitug could become the first FDA-approved treatment specifically targeting primary sclerosing cholangitis.