New results demonstrate seladelpar can reduce alkaline phosphatase and itching in patients with primary biliary cholangitis, a chronic liver disease.
Patients with primary biliary cholangitis, a chronic liver disease, were found to have high levels of interleukin-31 (IL-31), a cytokine believed to be involved in skin inflammation. Treating these patients with seladelpar led to reductions in IL-31 and the itching associated with primary biliary cholangitis, according to a post-hoc analysis of results from the phase 3 ENHANCE trial that was recently presented at the American College of Gastroenterology. The data were also published in Hepatology.
Primary biliary cholangitis (PBC) is a chronic liver disease that primarily affects women; about 130,000 total people in the United States are affected. PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, which leads to inflammation and destruction of the bile ducts. The most common early symptom is itching. Itching and fatigue can lead to lowered quality of life.
Current treatments — such as Actigall, Tricor and Ocaliva — have helped patients, but researchers said there is a need for therapies that also address the itch associated with the disease.
Seladelpar is a first-in-class oral, selective peroxisome proliferator-activated receptor (PPAR) delta agonist, or delpar. Preclinical and clinical data support its ability to regulate genes involved in bile acid synthesis, inflammation, fibrosis and lipid metabolism, storage, and transport.
“We know that severe itch is a debilitating symptom experienced by many people living with PBC,” Charles McWherter, Ph.D., CSO and president of research & development at CymaBay Therapeutics, told Managed Healthcare Executive. “Before this study, there has been limited understanding of the underlying pathology of itch in these patients.”
He said the findings presented at ACG suggest a correlation between the company’s seladelpar, IL-31 levels, and patient-reported itch. The presentation comes a day after the FDA has granted seladelpar an updated breakthrough therapy designation to now include itch in adults. This updated designation was based on data on seladelpar’s impact on the reduction in alkaline phosphatase and itching in patients without cirrhosis or with compensated cirrhosis.
“These results, and others we presented at the meeting, suggest patients with any level of ALP elevation are at risk of disease progression, reaffirm the potential of seladelpar as shown across clinical trials to improve disease markers, reduce symptom burden, and provide hope for a better overall quality of life,” he said.
Results from the ENHANCE trial were presented by Professor Andreas E. Kremer, M.D., Ph.D., department of Gastroenterology and Hepatology, University Hospital Zürich. “These results offer a glimmer of hope in that they link IL-31 levels in patients with PBC to itch,” he said in a press release. “This is a unique opportunity for researchers to further explore the relationship between the IL-31 pathway and itch, which may help us improve how we address an important, and often distressing, unmet need for patients.”
Results released in September 2023 from the phase 3 pivotal RESPONSE study also demonstrated reduction of itching after six months of treatment with seladelpar. The study found that of the 128 patients treated with seladelpar 61.7% met the primary composite endpoint related to serum alkaline phosphatase and bilirubin at 12 months versus 20.0% of patients on placebo. There were no treatment-related serious adverse events in the study. Seladelpar's tolerability profile appeared favorable and consistent with previous studies.
Additional analyses of RESPONSE are ongoing.