Immunic Says First Patient Enrolled in Proof-of-Concept Trial for Rare Liver Disease Therapy

Rare Daily Staff

Immunic said the first patient was enrolled in an investigator-sponsored proof-of-concept clinical trial of IMU-838 for the treatment of patients with the rare progressive liver disease primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a condition in which the bile ducts in the liver become inflamed, narrow, and prevent bile from flowing properly. The cause and disease mechanism are still unknown, but an autoimmune mechanism may play a role. There is an association with inflammatory bowel diseases, most often with ulcerative colitis and less commonly with Crohn’s disease. PSC has a prevalence of about 4.15 per 100,000 in the United States. Other than liver transplantation, there are currently no approved therapies that have been shown to improve survival in patients with PSC. The estimated time from diagnosis of PSC to death or liver transplant has been shown to be less than 15 years.

IMU-838 is an orally available, next-generation selective immune modulator that inhibits the intracellular metabolism of activated immune cells by blocking the enzyme dihydroorotate dehydrogenase.

The National Institutes of Health awarded a grant for the trial to Keith Lindor, senior advisor to the provost and professor of medicine at the College of Health Solutions, Arizona State University, and principal investigator for the trial.

The study will be sponsored by Elizabeth Carey, professor of medicine, division of gastroenterology and hepatology in the department of internal medicine at the Mayo Clinic, who has received Investigational New Drug approval from the U.S. Food & Drug Administration and has been granted Institutional Review Board approval to conduct the study. The study will be conducted at Mayo Clinic in Arizona and Minnesota, both of which are tertiary care centers for PSC patients.

The proof-of-concept study, for which Immunic is providing the study medication, is a single-arm, open-label, exploratory study planning to enroll a total of 30 patients with PSC, aged 18 to 75 years. The trial’s primary endpoint is the change in serum alkaline phosphatase (ALP) at six months compared to baseline. In previous trials, a biochemical endpoint such as change in serum ALP has been an accepted biomarker of disease progression in PSC patients.

“Recent studies indicate that the proinflammatory cytokine interleukin 17, or IL-17, may play a central role in the pathogenesis of PSC, as well as ulcerative colitis. Significant increases in IL-17-expressing lymphocytes are found in the livers of PSC patients,” said Arizona State University’s Lindor. “These findings speak to the strong possibility of an overlap in therapeutic approaches to the two diseases.”

Photo: Keith Lindor, senior advisor to the provost and professor of medicine at the College of Health Solutions, Arizona State University