Results were positive from a 120-day phase 2a study of CNP-104, a proposed treatment for primary biliary cholangitis (PBC), COUR Pharmaceuticals announced recently.
The clinical trial was the first-in-human, proof-of-concept, randomized trial to evaluate the tolerability, safety, efficacy and pharmacodynamics of CNP-104 among individuals 18 to 75 years of age who were not responsive to treatment with ursodeoxycholic acid (UDCA), obeticholic acid (OCA) or both, the company said.
“These data highlight the potential of CNP-104 to be the first disease-modifying treatment for people living with PBC,” said Paul M. Peloso, chief medical officer of COUR Pharmaceuticals, in a statement. “In addition to safety and tolerability data supporting further studies, we observed multiple immunological and clinical measurements supporting mechanistic proof of concept for CNP-104.”
Read more about PBC treatment and care
COUR observed positive results, including reduction in liver stiffness compared to placebo, suggesting that CNP-104 has the potential to halt disease progression, Peloso added.
Study findings
A total of 41 study participants were treated with CNP-104, dosed at 4 mg/kg or 8 mg/kg, or a placebo on days 1 and 8. All participants received two intravenous loading doses administered one week apart.
The study reported the following key findings from CNP-104 treatment.
- Slowing of disease progression in liver stiffness measured on Fibroscan, with a statistically significant differences between the active treatment vs. placebo at 120 days.
- Greater trending toward decreased albumin levels in the placebo group vs. the CNP-104 group.
- CNP-104 was linked to a favorable T-cell response in pathogenic T-cell populations and tolerance-inducing CD8 T cells.
- T helper 17 T cells decreased in number and percentage, with significantly higher response rates with CNP-104 vs. placebo at 120 days.
- CNP-104 was safe and well tolerated, with all treatment-related adverse events considered mild.
More study needed
CNP-104 is a biodegradable nanoparticle that encapsulates the E2 component of the mitochondrial PDC, which is recognized as being a key auto-antigen in patients with PBC. Treatment with CNP-104 intends to tackle the root cause of PBC by inducing tolerance to pathogenic activated PDC-E2 T cells that trigger bile duct inflammation, thus resulting in improved outcomes in liver health.
“Despite the recent evolution of the PBC treatment landscape, there remains a significant unmet need for new treatments,” said Christopher Bowlus, the Lena Valente professor and chief of the division of gastroenterology and hepatology at the University of California, Davis, and principal investigator for the current phase 2a study, in a statement. “Unlike CNP-104, current therapies do not address the root cause of the disease.” The “data are early and from a small number of patients, [but] they are incredibly promising and merit further investigation,” he added.
