Claims for Patent: 12,508,234

Summary for Patent: 12,508,234

Title:	Pharmaceutical formulation of odevixibat
Abstract:	The invention relates to a pharmaceutical formulation, e.g. a paediatric formulation, of odevixibat, which comprises a plurality of small particles. The formulation may be used in the treatment of liver diseases such as bile acid-dependent liver diseases, and particularly cholestatic liver diseases such as biliary atresia, progressive familial intrahepatic cholestasis (PFIC), Alagille syndrome (ALGS) and paediatric cholestatic pruritus. The invention also relates to a process for the preparation of the pharmaceutical formulation.
Inventor(s):	Eva Byröd, Per-Göran Gillberg, Anna-Maria Tivert, Rikard Bryland, Ann-Charlotte Dahlquist, Jessica Elversson, Nils Ove Gustafsson, Robert Lundqvist, Ingvar Ymen, Martin Bohlin
Assignee:	Eva Byroed Consulting AB , Tivert Konsult AB , Albireo AB
Application Number:	US18/475,930
Patent Claims:	1. A method for treating a liver disease comprising administering to a subject in need of such treatment a therapeutically effective amount of a pharmaceutical formulation of odevixibat, wherein the pharmaceutical formulation of odevixibat comprises a plurality of particles, wherein each particle is between about 0.1 and about 1.5 mm in size and contains odevixibat, or a pharmaceutically acceptable salt thereof, in an amount of from about 0.1% w/w to about 5.0% w/w based on the total weight of the particle, and wherein each particle comprises odevixibat agglomerates having a d90 particle size distribution of less than 15 μm. 2. The method according to claim 1, wherein the liver disease is a cholestatic liver disease. 3. The method according to claim 2, wherein the cholestatic liver disease is selected from the group consisting of: biliary atresia; progressive familial intrahepatic cholestasis (PFIC); Alagille syndrome (ALGS); and primary biliary cirrhosis (PBC). 4. The method according to claim 2, wherein the cholestatic liver disease is cholestatic pruritus. 5. The method according to claim 2, wherein the cholestatic liver disease is biliary atresia. 6. The method according to claim 5, wherein the biliary atresia is post-Kasai biliary atresia or post-liver transplantation biliary atresia. 7. The method according to claim 2, wherein the cholestatic liver disease is PFIC. 8. The method according to claim 7, wherein the PFIC is PFIC-1, PFIC-2, PFIC-3, non-specified PFIC, post-biliary diversion PFIC, or post-liver transplant PFIC. 9. The method according to claim 2, wherein the cholestatic liver disease is ALGS. 10. The method according to claim 1, wherein each particle contains odevixibat, or a pharmaceutically acceptable salt thereof, in an amount of from about 0.5% w/w to about 2.0% w/w based on the total weight of the particle. 11. The method according to claim 1, wherein each particle comprises a core and a coating layer surrounding the core. 12. The method according to claim 11, wherein the coating layer comprises odevixibat, or a pharmaceutically acceptable salt thereof. 13. The method according to claim 11, wherein the core does not contain odevixibat, or a pharmaceutically acceptable salt thereof. 14. The method according to claim 1, wherein odevixibat is present as a crystalline hydrate of odevixibat. 15. The method according to claim 1, wherein odevixibat is present as crystal modification 1 of odevixibat. 16. The method according to claim 15, wherein crystal modification 1 of odevixibat has an X-ray powder diffraction (XRPD) pattern, obtained with CuKα1-radiation, with at least specific peaks at °2θ positions 5.6±0.2, 6.7±0.2 and/or 12.1±0.2. 17. The method according to claim 1, wherein the subject is a pediatric subject. 18. A process for the preparation of a pharmaceutical formulation of odevixibat, the process comprising the step of preparing a homogeneous aqueous suspension of odevixibat. 19. The process according to claim 18, wherein the homogenous aqueous suspension is prepared by dispersing odevixibat in water by wet milling. 20. A process for the preparation of a pharmaceutical formulation of odevixibat, or a pharmaceutically acceptable salt thereof, the process comprising the steps of: a) wetting odevixibat in water using a homogenizer; b) dispersing the wetted odevixibat in water by wet milling, thereby obtaining a homogeneous aqueous suspension of odevixibat; and c) spraying the homogeneous aqueous suspension of odevixibat onto a plurality of cores, thereby forming a plurality of particles; wherein each particle is between about 0.1 and about 1.5 mm in size and contains odevixibat, or pharmaceutically acceptable salt thereof, in an amount of from about 0.1% w/w to about 5.0% w/w based on the total weight of the particle, and wherein each particle comprises odevixibat agglomerates having a d90 particle size distribution of less than 15 μm.