Mirum Pharmaceuticals (Nasdaq: MIRM) reported that maralixibat produced a statistically significant reduction in cholestatic pruritus versus placebo in the Phase III EXPAND study in patients with ultra-rare cholestatic liver diseases, including biliary atresia. The study also met all five prespecified secondary endpoints, supporting a planned US supplemental New Drug Application (sNDA) submission in H1 2027.
Maralixibat reversibly inhibits the ileal bile acid transporter (IBAT), decreasing reabsorption of bile acids from the ileum. EXPAND was a randomized, double-blind, placebo-controlled study enrolling 52 patients aged 6 months or older — 46 pediatric and 6 adults — with cholestatic pruritus associated with ultra-rare cholestatic liver diseases including biliary atresia. The primary endpoint, assessed in the all-pediatric population, was change from baseline in average worst-daily ItchRO(Obs) severity score during Weeks 13–20. Maralixibat produced a mean improvement of 1.81 points versus 0.83 points for placebo, a treatment difference of 0.98 points (p=0.0004).
The study also met all five prespecified secondary endpoints, including pruritus improvement on 86.0% of days with maralixibat versus 49.1% with placebo (p=0.0008) in pediatric patients, and a 70.1% reduction in total serum bile acids versus 3.5% for placebo (p<0.0001). The small sample size — primary analysis based on 22 maralixibat-treated and 24 placebo-treated pediatric patients — and the 20-week observation window limit the scope of these results.
In the biliary atresia with native liver subgroup, maralixibat produced an ItchRO(Obs) improvement of 2.16 points versus 1.01 points for placebo (p=0.0002), though this subgroup comprised only 11 maralixibat-treated and 14 placebo-treated patients.
Mirum said safety findings were consistent with prior clinical experience with maralixibat and that no new safety signals were observed, with diarrhea reported in 64.0% of maralixibat-treated patients versus 11.1% on placebo, Grade 3 or higher treatment-emergent adverse events in 24.0% versus 22.2%, and no treatment-emergent adverse events leading to death in either arm.