What is Primary Biliary Cholangitis?
Primary biliary cholangitis (PBC) is a chronic autoimmune disease that degrades the bile ducts embedded in the liver, and if left untreated, leads to cirrhosis. Over time, this chronic inflammation causes a toxin build-up in the bloodstream, which is thought to induce neuroinflammation – inflammation in the brain.
PBC primarily affects women, with symptoms debuting around the age of 40–60. Approximately 60-80% of all patients develop fatigue and about 30% develop central fatigue – an especially debilitating form of fatigue with cognitive dysfunction that originates from the brain and that causes a lack of motivation, incapacitated decision-making and inability to cope with everyday activities. For patients, this form of fatigue leads to a significant deterioration in quality of life, including reduced sociability and working capacity.
As the bile ducts are attacked, the degree of inflammation in the brain increases, leading to personality changes, confusion, reduced level of consciousness and increased fatigue.
Today, approximately 190,000 patients live with PBC in the seven largest geographical pharmaceutical markets (United States, France, Germany, Italy, Spain, the UK, and Japan).
Current treatments and therapeutic opportunities
There are currently no curative treatments for PBC. There are limited number of approved drugs for PBC, inducing ursodeoxycholic acid (UDCA), Iqirvo®, and Livdelzi®. Until recently, obeticholic acid (OCA; OCALIVA®) was also approved. UDCA, Iqirvo®, and Livdelzi® are used to reduce the risk of progression of the disease into cirrhosis of the liver but not for cognitive dysfunction or fatigue. Umecrine Cognition is the only clinical-stage company in the world currently developing a drug candidate that directly aims to counteract the central nervous symptoms associated with PBC.
Umecrine Cognition’s phase 1B/2A clinical study
The company is currently conducting a two-part, randomized, double-blind, placebo-controlled, two-part Phase 1b/2a study of golexanolone versus placebo among PBC subjects with clinically significant fatigue and cognitive symptoms on a stable background of standard-of-care PBC treatment. Following an interim analysis to support appropriate dosing, the second part of the study evaluates the safety and preliminary efficacy of two dose levels of golexanolone, versus placebo, following a twice-a-day orally administered treatment of 28 days. The second part is presently ongoing and enrolling patients, read more about it here. To evaluate the treatment efficacy, a new, validated clinical symptom scale CGI-S-PBC™ has been developed.
Clinically validated tool to measure symptom improvement
The CGI-S-PBC™ scale is designed to measure symptom severity, especially fatigue and cognitive dysfunction, in PBC patients. The scale is based on structured interviews of PBC patients by experts and was created as a more objective measurement to address the lack of reliable tools for tracking symptoms that aren’t captured by standard lab tests, which is a key target of golexanolone.
The CGI-S-PBC™ was developed from and as a complement to the widely used patient reported outcomes measure PBC-40 and is currently being used and further validated in the 1b/2a study to help evaluate golexanolone’s effect on brain-related symptoms and connect preclinical findings to measurable clinical outcomes.