- First and only data evaluating IBAT inhibition in treating primary sclerosing cholangitis (PSC)
- Data provided proof-of-concept for Phase 2b VISTAS study evaluating volixibat, an IBAT inhibitor, in patients with PSC
Mirum Pharmaceuticals, Inc. (NASDAQ:MIRM) today announced that Hepatology Communications published data from the CAMEO study evaluating the safety, tolerability, and efficacy of LIVMARLI® (maralixibat) oral solution in patients with primary sclerosing cholangitis (PSC).
The CAMEO study was the first proof-of-concept study evaluating an ileal bile acid transporter (IBAT) inhibitor in patients with pruritus associated with PSC, a cholestatic liver disease. The open-label study (n=27) evaluated the safety and tolerability of LIVMARLI for 14 weeks in adults with PSC measuring pruritus, serum bile acid levels, and liver function.
In this open-label Phase 2 pilot study, pruritus scores and serum bile acid concentration decreased over the 14 weeks of treatment with LIVMARLI. Participants whose sBA was elevated above normal at baseline achieved a 40% reduction (n=18). Similarly, participants with an average pruritus score of ≥3 out of 10 at baseline achieved a 70% improvement in pruritus (n=8). (The most common treatment emergent adverse events (TEAEs) were gastrointestinal related (diarrhea, nausea, and abdominal pain). The TEAEs were generally tolerable and consistent with the expected mechanism of action of IBAT inhibitors.
The full publication including additional data from the analysis can be accessed in Hepatology Communications.
“PSC is a rare, chronic, progressive cholestatic liver disease. Patients with PSC frequently suffer from severe pruritus that negatively impacts their quality of life,” said Christopher Bowlus, MD, chief of gastroenterology and hepatology at University of California, Davis, and lead author on the publication. “Treatment options for pruritus in patients with PSC are limited and unproven. The early data observed in the CAMEO study provides evidence that IBAT inhibitors may provide benefit to patients with PSC suffering from pruritus.”
“These are the first published data on the potential for IBAT inhibition for the treatment of patients with PSC,” said Pam Vig, PhD, head of research and development at Mirum. “The CAMEO study with LIVMARLI lays the foundation for the Phase 2b VISTAS study with volixibat, a minimally absorbed IBAT inhibitor, which is currently recruiting patients. We are grateful to the clinicians and patients who participated in the CAMEO study and thank them for their contribution.”
About Primary Sclerosing Cholangitis
Primary sclerosing cholangitis (PSC) is a rare, serious, idiopathic chronic cholestatic liver disease characterized by cholestasis, progressive inflammation, and destruction of bile ducts, which may lead to fibrosis, cirrhosis, portal hypertension, cancer, and ultimately liver failure. It is estimated that approximately 29,000 people in the United States and approximately 50,000 people in Europe suffer from PSC with no approved therapies. The underlying etiology of PSC is not completely understood, but it is thought to arise from a combination of genetic and environmental factors. The median age at diagnosis is approximately 35 years, and approximately 70% of PSC patients have inflammatory bowel disease, principally ulcerative colitis. Signs and symptoms of PSC may include, but are not limited to, pruritus, extreme fatigue, jaundice, and abdominal discomfort. The eventual buildup of bile acids from continued bile duct injury and obstruction damages liver cells and is thought to contribute to the progression of liver failure. Complications involving the biliary tree are common and include cholangitis, as well as ductal strictures and gallstones, the latter of which frequently require endoscopic or surgical interventions. PSC also increases the risk of development of malignancies, with cholangiocarcinoma being the most common. PSC is the fifth leading indication for liver transplantation; however, the post-transplant recurrence rate of PSC is up to 25%.
