LIVMARLI (maralixibat) - Progressive intrahepatic cholestasis (PFIC)

The Committee deems that the clinical benefit of LIVMARLI 9.5 mg/mL (maralixibat) oral solution is substantial in the MA indication.

Considering:

• the demonstrated superiority of maralixibat versus placebo after 26 weeks on reduction of the pruritus severity score in a paediatric population with type 2 PFIC (with the exception of subtype BSEP3) with a clinically relevant effect size (primary endpoint), as well as statistically significant results for clinically relevant ranked secondary endpoints, i.e. the reduction in serum bile acid levels in this same population, and the results for these same endpoints in a broader population of paediatric patients with PFIC type 3, 4 and 6,
• the absence of a significant difference between maralixibat and placebo for the fourth secondary endpoint relative to the proportion of pruritus responders in the main cohort, interrupting the analysis of the subsequent ranked secondary endpoints,
• uncertainties concerning the long-term efficacy of maralixibat, particularly with respect to recourse to surgery and prevention of the development of hepatocellular carcinoma,
• the lack of robust assessment of the impact on quality of life of maralixibat, which is regrettable in this disease with a marked impact on the quality of life of patients and their families,
• the safety profile of LIVMARLI (maralixibat), which appears to be favourable in the paediatric population, with limited follow-up however,
• the benefit of an oral solution form of LIVMARLI (maralixibat) suitable for administration in children from 3 months of age,
• the concomitant development with BYLVAY (odevixibat), not enabling direct comparison with maralixibat in the phase 3 study,

the Committee deems that LIVMARLI 9.5 mg/mL (maralixibat) oral solution provides a moderate clinical added value (CAV III), in PFIC type 1 and 2 (with the exception of subtype BSEP3) in the same way as BYLVAY (odevixibat) and in the other types of PFIC, in the current care pathway, which includes the relevant comparators.