Nebokitug shows sustained benefits for moderate, advanced PSC
Year's treatment reduces occurrence of disease progression events, biomarkers
A year of treatment with Chemomab Therapeutics’s candidate nebokitug reduces key disease biomarkers and the occurrence of clinical events that reflect disease progression among adults with primary sclerosing cholangitis (PSC).
These findings, from the open-label extension (OLE) part of the Phase 2 SPRING clinical trial (NCT04595825), are consistent with positive data from the study’s initial 15-week, placebo-controlled portion. In both parts, the benefits were most pronounced in participants with moderate to advanced disease who received nebokitug at its highest tested dose.
“We are delighted that nebokitug continued to be safe and well-tolerated … and showed broad and substantial improvements in all the key biomarkers associated with PSC,” Adi Mor, PhD, co-founder and CEO of Chemomab, said in a company press release. “These are great news for Chemomab and for patients with PSC, a debilitating disorder that lacks any FDA-approved treatments and too often results in liver transplantation or death.”
Mor said the promising results support the therapy’s potential “to alter the course of PSC, as well as the rationale for the planned Phase 3 trial that provides a clear pathway to potential full regulatory approval.” The upcoming study will test if nebokitug at 20 mg/kg can delay clinical events related to disease progression over a placebo among 350 PSC patients, most of whom will have moderate or severe disease.
The hallmark complication of PSC is chronic cholangitis, or inflammation in the bile ducts, the series of tubes that carry the digestive fluid bile from the liver to the small intestine. Bile duct damage and scarring (fibrosis) over time lead to cholestasis, or stalled bile flow, that can eventually cause permanent liver fibrosis and liver failure.
Previously called CM-101, nebokitug is intended to neutralize CCL24, a protein involved in driving signaling pathways that contribute to PSC. The treatment should ease inflammation and fibrosis, thereby preventing PSC-related damage and slowing disease progression.
SPRING results
SPRING enrolled 76 adults with PSC who were randomly assigned to nebokitug (10 or 20 mg/kg) or a placebo, given via infusion into the bloodstream once every three weeks for 15 weeks, or just under four months.
Top-line data showed the treatment led to reductions in biomarkers of liver fibrosis, inflammation, and cholestasis, with greater benefits seen in those with moderate or advanced disease. Nebokitug also may be able to ease intense itching called pruritus, a common PSC symptom.
After completing the trial’s placebo-controlled part, 93% of eligible participants joined its OLE part, where all are receiving 10 or 20 mg/kg of nebokitug for about 7.5 months. That’s nearly a year of total treatment for those originally assigned to nebokitug.
The new results show that, for those on nebokitug since the start of SPRING, treatment was generally associated with continued stabilizations or reductions in biomarkers of liver damage, fibrosis, and cholestasis, with the greatest benefits seen at 20 mg/kg and in those with moderate or advanced disease.
Reduced markers of disease; reduced risk of clinical events
One such marker was the Enhanced Liver Fibrosis (ELF) score, a noninvasive estimate of liver fibrosis based on blood test findings where a higher score is associated with a greater risk of liver disease progression. ELF scores were generally stable after 48 weeks, with a tendency toward less liver fibrosis in those with moderate/advanced disease who received the 20 mg/kg dose.
Liver stiffness, another noninvasive indicator of fibrosis, was significantly reduced in patients with moderate or advanced disease given nebokitug compared with a historical control group of untreated people with PSC.
“Since PSC is a chronic, slowly progressive disease, it was important to demonstrate that the positive results reported from the 15-week … Phase 2 study were durable over a longer period of treatment,” Mor said.
Nebokitug also appeared to reduce the risk of disease-related clinical events, including liver transplant, death, or liver decompensation, where the liver is substantially damaged and can no longer perform its usual functions. Particularly, significantly fewer nebokitug-treated patients with moderate or severe disease had a clinical event after a year over those from the historical control group (4.8% vs. 25.8%).
For those who switched to nebokitug from the placebo, benefits were similar to those for nebokitug-treated participants in the placebo-controlled portion, with stabilizations in ELF scores and reductions in liver stiffness, according to Chemomab.
Nebokitug was safe and well tolerated throughout the OLE portion.
“The fact that nebokitug continued to be generally well tolerated and to generate continued improvements across a broad range of disease-related biomarkers is very encouraging,” said Douglas Thorburn, MD, a SPRING’s investigator of the Royal Free London NHS Foundation Trust and University College London. “I look forward to the continued clinical progress of nebokitug as a potential new therapy for PSC where there is so much unmet medical need.”
About the Author
