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Maralixibat, an inhibitor of the ileal bile acid transporter, is approved in the EU for treatment of Progressive Familial Intrahepatic Cholestasis (PFIC) in individuals ≥3 months. Prior analyses in ALGS have demonstrated improved event-free survival (EFS) following use of maralixibat and this improvement is associated with reductions in sBA. Data from MARCH/MARCH-ON, a clinical trial of maralixibat for individuals with PFIC, demonstrated reductions in sBA. In this analysis, we evaluated the impact of sBA reduction on EFS.The design of MARCH/MARCH-ON have been previously described. Data were administratively censored in June, 2023. First events (i.e., liver transplant, decompensation, surgical biliary diversion [SBD], or death) were identified for different PFIC types. For individuals with nt-BSEP and FIC1, 2-year EFS was calculated and stratified by sBA response at Week 26 (averaged over last 12 weeks) using thresholds developed by the NAPPED Consortium (BSEP: >75% reduction or <102 µmol/L; FIC1: <65 µmol/L).There were 5 events (nt-BSEP: 1 transplant, 1 decompensation; FIC1: 1 death, 1 SBD; and MDR3: 1 transplant) among 72 individuals with a median (Q1, Q3) follow-up of 94 (68, 110) weeks. The overall EFS was 92%. Among individuals with nt-BSEP, an sBA response was achieved in 12 of 27 (44%), and this group had no events yielding an EFS of 100%; an insufficient sBA response was observed in 15 (56%) and this group had 2 events yielding an EFS of 84%. The sBA reduction for the 2 patients with events were 19% and 26%. Among individuals with FIC1, an sBA response was achieved in 3 of 12 (25%) and this group had no events yielding an EFS of 100%; an insufficient sBA response was observed in 9 (75%) and this group had 2 events for an EFS of 78%. The sBA reduction for the 2 patients with events were 18% and 16%. When nt-BSEP and FIC1 were analyzed together, sBA responders had an EFS of 100% whereas sBA non-responders had an EFS of 81%. For the individual with MDR3 disease requiring a transplant, the sBA reduction was 44%.Consistent with sBA response thresholds from the NAPPED Consortium that are associated with EFS, individuals in MARCH/MARCH-ON who reduced sBA levels below the threshold did not have a clinically meaningful event whereas some individuals who had lower reductions in sBA experienced events. These data support the importance of sBA reduction in PFIC and the potential of maralixibat to facilitate this biochemical change.