Mirum Pharmaceuticals Completes Enrollment in Phase 2b VISTAS Study for Primary Sclerosing Cholangitis Treatment
核心洞察
Mirum Pharmaceuticals has completed enrollment in the Phase 2b VISTAS study evaluating volixibat, an oral IBAT (搜索) inhibitor, for treating cholestatic pruritus (搜索) in primary sclerosing cholangitis (搜索) patients.
The trial previously met pre-specified efficacy and safety thresholds at a blinded interim analysis in 2024, with topline results expected in the second quarter of 2026.
Primary sclerosing cholangitis (搜索) is a rare, progressive liver disease with no currently approved therapies, leaving patients with limited treatment options focused on symptom management.
Mirum Pharmaceuticals has achieved a significant milestone in rare liver disease research by completing enrollment in the Phase 2b VISTAS study of volixibat, an investigational oral IBAT (搜索) inhibitor for treating cholestatic pruritus (搜索) in patients with primary sclerosing cholangitis (搜索) (PSC). The trial previously met its pre-specified efficacy and safety thresholds at the blinded interim analysis for dose selection conducted in 2024, with topline results expected to be announced in the second quarter of 2026.
"Completing enrollment in VISTAS is a major milestone for the PSC community and for Mirum," said Joanne Quan, M.D., Chief Medical Officer. "This progress reflects the dedication of patients, investigators, and our team working together toward the shared goal of addressing the daily challenges of PSC, including persistent itch and fatigue. We believe the data generated from VISTAS will be an important step toward bringing meaningful medicines to patients who currently have no approved therapies."
Study Design and Endpoints
The VISTAS study (NCT04663308) is a global, randomized, double-blind, placebo-controlled Phase 2b trial evaluating the efficacy and safety of volixibat in patients with primary sclerosing cholangitis (搜索) and cholestatic pruritus (搜索) over a 28-week period. The primary endpoint is a reduction in pruritus as measured by the Adult ItchRO, a pruritus numerical rating scale ranging from 0 (no itch) to 10 (worst possible itch). Secondary endpoints include assessments of fatigue, serum bile acids, and safety.
Addressing an Unmet Medical Need
Primary sclerosing cholangitis (搜索) is a rare, chronic, progressive liver disease in which the bile ducts inside and outside the liver become inflamed, scarred, and narrowed over time. This bile duct damage leads to bile accumulation, liver injury, and eventually liver failure. Patients with PSC experience a heavy symptom burden, with pruritus (severe itching), fatigue, and abdominal pain that may be debilitating and life-altering. Beyond symptom burden, PSC is associated with increased risk of bile duct cancer and need for liver transplantation. There are currently no approved therapies for PSC, leaving patients with limited treatment options focused on symptom management and supportive care.
Ricky Safer, CEO and Founder of PSC Partners Seeking a Cure (搜索), a patient-led advocacy organization dedicated to supporting those affected by PSC, emphasized the significance of this milestone: "PSC Partners is thrilled to see Mirum reach this important milestone with the VISTAS study. Completing enrollment marks a significant step forward in advancing a possible treatment for itch in PSC, bringing tremendous hope to our community."
Volixibat's Mechanism and Development Program
Volixibat is an oral, minimally absorbed agent designed to selectively inhibit the ileal bile acid transporter (IBAT (搜索)). Volixibat may offer a novel approach to the treatment of adult cholestatic diseases by blocking the recycling of bile acids, through inhibition of IBAT, thereby reducing bile acids systemically and in the liver.
The drug is currently being evaluated in Phase 2b studies for primary sclerosing cholangitis (搜索) (VISTAS study) and primary biliary cholangitis (搜索) (VANTAGE study). In 2024, Mirum announced positive interim results from the Phase 2b VANTAGE study showing statistically significant improvement in pruritus as well as meaningful reductions in serum bile acids and improvements in fatigue for patients treated with volixibat. No new safety signals were observed, and the most common adverse event was diarrhea with all cases mild to moderate.
Volixibat has been granted breakthrough therapy designation for the treatment of cholestatic pruritus (搜索) in patients with primary biliary cholangitis (搜索). The VANTAGE study for primary biliary cholangitis is expected to complete enrollment in 2026 and announce topline results in the first half of 2027.
Company Pipeline and Approved Therapies
Mirum Pharmaceuticals is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. The company has three approved medications: LIVMARLI (maralixibat) oral solution/tablets, CHOLBAM (cholic acid) capsules, and CTEXLI (chenodiol) tablets.
LIVMARLI, an IBAT (搜索) inhibitor, is approved for the treatment of two rare liver diseases affecting children and adults. It is approved for the treatment of cholestatic pruritus (搜索) in patients with Alagille syndrome (搜索) in the U.S. (three months and older), in Europe (two months and older), and in other regions globally. It is also approved in the U.S. for cholestatic pruritus in PFIC (搜索) patients 12 months of age and older; in Europe, it is approved for patients with PFIC three months of age and older.
Mirum's late-stage pipeline includes volixibat being evaluated in two potentially registrational studies and plans for a Phase 2 study evaluating MRM-3379, a PDE4D (搜索) inhibitor for the treatment of Fragile X syndrome (搜索), a rare genetic neurocognitive disorder.