お知らせ • May 06
Mirum Pharmaceuticals Announces Primary Endpoint Met In VISTAS Study Of Volixibat In Patients With Primary Sclerosing Cholangitis
Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) announced the primary endpoint was met in the VISTAS Phase 2b study evaluating volixibat, an investigational oral ileal bile acid transporter (IBAT) inhibitor, in patients with primary sclerosing cholangitis (PSC). The VISTAS Phase 2b study included 158 patients with PSC who were assigned to either a primary analysis cohort (moderate to severe itch; n=111) or a secondary analysis cohort (mild itch; n=47) based on itch severity at baseline, as measured by the Adult Itch Reported Outcome (ItchRO) scale. Patients in both cohorts were treated with volixibat 20 mg twice daily (BID) or placebo. Per the study protocol, the endpoint was evaluated in the primary analysis cohort. The results of the VISTAS Phase 2b study support the potential for volixibat to become the first treatment for cholestatic pruritus in patients with PSC. In the primary analysis cohort, treatment with volixibat demonstrated a robust 2.72 point improvement in pruritus and a placebo-adjusted difference of 1.64 points in the primary endpoint (pChange from Baseline (Primary Analysis Cohort) table. Volixibat’s safety profile was generally consistent with the known effects of IBAT inhibition, characterized primarily by gastrointestinal adverse events and elevations in liver laboratory parameters, including alanine aminotransferase (ALT) and bilirubin. Key safety data from the VISTAS Phase 2b study are presented below in the Safety Summary (Primary and Secondary Cohorts) table. Mirum has a pre-New Drug Application (NDA) meeting for volixibat in PSC scheduled with the U.S. FDA in summer 2026, with a planned NDA submission in the second half of 2026. The full results from the VISTAS Phase 2b study will be presented in a late-breaking oral presentation at the European Association for the Study of the Liver (EASL) International Liver Congress on May 30 at 2:15 p.m. CEST. Mirum also now expects topline data from its VANTAGE Phase 2b study of volixibat in primary biliary cholangitis (PBC) in the first quarter of 2027. Change from Baseline (Primary Analysis Cohort) Volixibat 20 mg BID (n=54) Placebo (n=57) Difference (VLX - PBO) LS Mean change in Adult ItchRO (SE) -2.72 (0.240) -1.08 (0.241) -1.64 =2 point reduction in Adult ItchRO 55.6% 26.3% 29.3% 0.0019 LS Mean changes in sBA (SE) -33.7 (12.14) 2.1 (11.87) -35.8 0.0324 *Adult ItchRO is an 11-point scale (0 = no itch; 10 = worst itch imaginable). LSMean = model-adjusted mean from a mixed model for repeated measures (MMRM). Values represent change from baseline to the average of the last 12 weeks of treatment (weekly averaged worst daily itch score). Safety Summary (Primary and Secondary Cohorts) Volixibat 20 mg BID (n=77) Placebo (n=81) Participants with any treatment emergent adverse event (TEAE), n (%) 72 (93.5) 68 (84.0) Grade 3 or higher TEAEs 10 (13.0) 9 (11.1) Serious TEAEs 8 (10.4) 5 (6.2) TEAE that led to death 0 1 (1.2) TEAE that led to premature discontinuation from study 7 (9.1) 2 (2.5) Study discontinuation due to diarrhea 3 (3.9) 1 (1.2) Additional safety observations: Serious adverse events (SAEs) in volixibat treated patients included cholangitis, infection (sepsis, liver abscess, viral infection), abdominal pain, cholangiocarcinoma, sclerosing cholangitis, biliary colic, pyrexia, back pain, procedure-related pancreatitis; none related. SAEs in placebo patients included cholangitis, constipation, spontaneous bacterial peritonitis, liver function tests increases, radius fracture. Elevations in ALT, Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and bilirubin were observed more frequently in volixibat treated patients than placebo treated patients. Mirum will host a conference call at 8:30 am ET to discuss topline results from the VISTAS Phase 2b study, along with previously announced topline results from the Phase 2b portion of the AZURE-1 study of brelovitug in HDV. Volixibat is an oral, minimally absorbed agent designed to selectively inhibit the ileal bile acid transporter (IBAT). Volixibat may offer a novel approach in 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. Volixibat is currently being evaluated in phase 2b studies for primary sclerosing cholangitis (PSC) (VISTAS study) and primary biliary cholangitis (PBC) (VANTAGE study). In 2024, the Phase 2b VANTAGE study of volixibat in PBC met the primary endpoint. No new safety signals were observed, and the most common adverse event was diarrhea with all cases mild to moderate. Volixibat has been granted FDA Breakthrough Therapy designation for the treatment of PBC. VISTAS is a global, randomized, double-blind, placebo-controlled Phase 2b study evaluating the efficacy and safety of volixibat in patients with cholestatic pruritus caused by primary sclerosing cholangitis (PSC). The primary endpoint of the study was mean change in weekly averaged daily itch score, as measured by the adult ItchRO scale (an 11-point scale where 0 = no itch and 10 = worst itch imaginable), from baseline to Week 28, defined as the average of the last 12 weeks of treatment. PSC 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 often leads to bile accumulation, cholangitis, liver injury, and eventually liver failure. The disease impacts an estimated 30,000 patients in the United States. Patients with PSC experience a heavy symptom burden, with pruritus (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.