Indirect Comparison of Maralixibat and Odevixibat for the Treatment of Progressive Familial Intrahepatic Cholestasis.

Purpose: Recent clinical trials provide evidence of the efficacy and safety of 2 ileal bile acid transporter inhibitors, maralixibat and odevixibat, for the treatment of children with progressive familial intrahepatic cholestasis (PFIC). However, no head-to-head trial currently exists assessing the efficacy of these 2 treatments. The objective of this study was to generate estimates of comparative efficacy and safety between maralixibat and odevixibat to inform optimal practices for the treatment of children with PFIC.

Methods: Two phase 3 randomized placebo-controlled trials, MARCH-PFIC (maralixibat: n = 16; placebo: n = 19) and PEDFIC-1 (odevixibat: n = 42; placebo: n = 20), were included in an indirect treatment comparison (ITC) anchored by the placebo arms of each trial. Using patient-level data from MARCH-PFIC and published aggregate data from PEDFIC-1, we generated estimates of comparative efficacy for endpoints that were consistent between trials, including the proportion of patients achieving a serum bile acid (sBA) response and change from baseline in sBA concentration.

Findings: Comparisons of the proportion of sBA responders indicated that maralixibat was significantly more efficacious than odevixibat (120 µg/kg), with an estimated treatment difference of 32.3% (95% CI, 1.1% to 63.4%, P = 0.043). In addition, point estimates for change from baseline in sBA concentration and total bilirubin trended in favor of maralixibat. These findings were robust to adjustments for imbalances in patient demographic characteristics between trials. No statistically significant differences were observed for alanine transaminase, aspartate transaminase, or gamma-glutamyl transferase. The safety profiles of maralixibat and odevixibat were comparable, although adverse events associated with maralixibat were typically milder than those with odevixibat (mild: 75% vs 45%; moderate: 25% vs 31%; severe: 0% vs 7%).

Implications: These findings suggest that maralixibat provides additional clinical benefit for children with PFIC compared with odevixibat in terms of increasing the proportion of sBA responders. Further studies are needed to compare the ability of maralixibat and odevixibat to reduce pruritus and improve long-term outcomes, including patients' quality of life.