COUR Pharmaceuticals has announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to CNP-104 for the treatment of primary biliary cholangitis (PBC). This designation underscores the potential of CNP-104 as a disease-modifying treatment for individuals with PBC.
The Orphan Drug Designation follows the presentation of positive topline data from the Phase 2a clinical trial of CNP-104 in PBC at The Liver Meeting 2024. Dannielle Appelhans, President and CEO of COUR, stated that the designation highlights CNP-104's potential to be the first disease-modifying treatment for PBC. The Phase 2a data demonstrated favorable T cell responses and a statistically significant reduction in liver stiffness, as measured by FibroScan, by day 120 of the study period.
CNP-104: A Novel Approach to PBC Treatment
CNP-104 is a biodegradable nanoparticle encapsulating the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC), a key autoantigen in PBC. The therapy aims to address the underlying cause of PBC by inducing tolerance to pathogenic activated PDC-E2 T-cells, which drive inflammation in bile ducts. This approach has the potential to improve clinical outcomes and liver health.
Clinical Trial Data and Outcomes
The Phase 2a trial (NCT05104853) evaluated the safety, tolerability, and efficacy of CNP-104 in patients with PBC already undergoing treatment with ursodeoxycholic acid and/or obeticholic acid. Patients were randomized to receive either 4 mg/kg or 8 mg/kg of CNP-104 or a placebo via intravenous infusion on days 1 and 8, with a 120-day follow-up period.
Results from the trial indicated that patients treated with CNP-104 experienced a reduction in antigen-specific Th17 T cells compared to the placebo group. While alkaline phosphatase (ALP) levels did not significantly differ between the groups, a statistically significant difference in liver stiffness, measured by vibration-controlled transient elastography, was observed, with the placebo group showing an increase and the CNP-104 group demonstrating stability. Liver biopsies from a subset of patients suggested a reduction in PanCK+ and CD3–CD4+ cells, which are markers of ductal pathology.
The treatment was generally well-tolerated, with most adverse events being mild in severity. No drug-related serious adverse events or deaths were reported.
Significance of Orphan Drug Designation
The FDA grants Orphan Drug Designation to encourage the development of treatments for rare diseases affecting fewer than 200,000 people in the United States. This designation provides several benefits, including tax credits for qualified clinical trials, exemption from user fees, and the potential for seven years of market exclusivity upon regulatory approval.
CNP-104 had previously received Fast Track Designation from the FDA in January 2022, making it eligible for Accelerated Approval and Priority Review if specific criteria are met.
PBC: An Unmet Medical Need
Primary biliary cholangitis is a chronic, life-threatening autoimmune disease of the liver that disproportionately affects women and is a leading cause of liver transplants in this population. PBC is characterized by impaired bile flow (cholestasis) and the accumulation of toxic bile acids in the liver, which can lead to fibrosis, cirrhosis, and ultimately liver failure. Symptoms such as fatigue and pruritus (severe itching) significantly affect patients’ quality of life.
While existing treatments like ursodeoxycholic acid can manage symptoms, there remains a need for therapies that address the underlying cause of the disease and modify its progression. The recent accelerated approvals of Iqirvo (elafibranor) and Livdelzi (seladelpar) have expanded treatment options, but CNP-104 represents a novel approach with the potential to induce immune tolerance and alter the course of PBC.
Future Directions
COUR Pharmaceuticals is collaborating with clinical advisors and key opinion leaders to advance CNP-104 to the next phase of clinical development. The company's focus remains on developing therapies that target the root cause of autoimmune diseases through antigen-specific immune tolerance.
