Claims for Patent: 12,533,340

Summary for Patent: 12,533,340

Title:	Treatment of autoimmune disease in a patient receiving additionally a beta-blocker
Abstract:	The present invention relates to methods of treating autoimmune diseases with siponimod in patients receiving additionally a beta-blocker.
Inventor(s):	Eric Legangneux, Alexandros Sagkriotis, Pierre Jordaan, Florine Polus, Alan John Camm, Shibadas Biswal, Parasar Pal, Uday Kiran Veldandi, Atul Keshav Pawar, Vassilios Aslanis, Kasra Shakeri-Nejad
Assignee:	Novartis AG
Application Number:	US18/352,999
Patent Claims:	1. A method of treating multiple sclerosis in a patient receiving a chronic beta-blocker treatment and having a resting heart rate of >50 bpm under said chronic beta-blocker treatment comprising introducing in said patient a siponimod treatment by a) administering to said patient an initial titration regimen of siponimod; and b) administering to said patient 1-15 mg siponimod daily as a maintenance regimen; wherein said initial titration regimen comprises administering siponimod at a dosage lower than the dosage of the maintenance regimen and then increasing the dosage stepwise up to the dosage of the maintenance regimen. 2. The method of claim 1, wherein the multiple sclerosis is secondary progressive multiple sclerosis. 3. The method of claim 1, wherein the multiple sclerosis is relapsing-remitting multiple sclerosis. 4. The method of claim 1, wherein the maintenance regimen administered in step b) of said method comprises 2-10 mg siponimod. 5. The method of claim 1, wherein said maintenance regimen comprises 2-5 mg siponimod. 6. The method of claim 1, wherein the maintenance regimen administered in step b) of said method is administered once daily. 7. The method of claim 1, wherein the maintenance regimen administered in step b) of said method is administered as an immediate release dosage form. 8. The method of claim 1, wherein said initial titration regimen comprises administering siponimod such that the dosage administered on a specific day of the initial titration regimen is the sum of the dosages administered on the previous two days within a range of ±40%. 9. The method of claim 1, wherein the dosage of the maintenance regimen is 2 mg siponimod and wherein said initial titration regimen comprises administering 0.25 mg siponimod at day 1, 0.25 mg of siponimod at day 2, 0.5 mg siponimod at day 3, 0.75 mg siponimod at day 4, 1.25 mg siponimod at day 5, and 2 mg siponimod at day 6. 10. The method of claim 1, wherein said initial titration regimen comprises one administration of 0.25 mg siponimod at day 1, one administration of 0.25 mg siponimod at day 2, one administration of 0.5 mg siponimod at day 3, one administration of 0.75 mg siponimod at day 4, one administration of 1.25 mg siponimod at day 5, and one administration of 2 mg siponimod at day 6. 11. A method of treating multiple sclerosis in a patient receiving a chronic beta-blocker treatment and having a resting heart rate of ≤50 bpm under said chronic beta-blocker treatment comprising: a) interrupting said chronic beta-blocker treatment in said patient until the baseline heartrate is >50 bpm; b) initiating in said patient a siponimod treatment by b1) administering to said patient an initial titration regimen of siponimod; and b2) administering to said patient 1-15 mg siponimod daily as a maintenance regimen; and c) re-initiating in said patient a beta-blocker treatment the earliest at the first day when said patient is receiving the dosage of the maintenance regimen. 12. The method of claim 11, wherein the multiple sclerosis is secondary progressive multiple sclerosis. 13. The method of claim 12, wherein the multiple sclerosis is relapsing-remitting multiple sclerosis. 14. The method of claim 11, wherein the maintenance regimen administered in step b2) of said method comprises 2-10 mg siponimod. 15. The method of claim 11, wherein said maintenance regimen comprises 2-5 mg siponimod. 16. The method of claim 11, wherein the maintenance regimen administered in step b2) of said method is administered once daily. 17. The method of claim 11, wherein the maintenance regimen administered in step b2) of said method is administered as an oral dosage form. 18. The method of claim 11, wherein the maintenance regimen administered in step b2) of said method is administered as an immediate release dosage form. 19. The method of claim 11, wherein said initial titration regimen comprises administering siponimod such that the dosage administered on a specific day of the initial titration regimen is the sum of the dosages administered on the previous two days within a range of ±40%. 20. The method of claim 11, wherein said initial titration regimen is conducted over 3-10 days. 21. The method of claim 11, wherein the dosage of the maintenance regimen is 2 mg siponimod and wherein said initial titration regimen comprises administering 0.25 mg siponimod at day 1, 0.25 mg of siponimod at day 2, 0.5 mg siponimod at day 3, 0.75 mg siponimod at day 4, 1.25 mg siponimod at day 5, and 2 mg siponimod at day 6. 22. The method of claim 11, wherein said initial titration regimen comprises one administration of 0.25 mg siponimod at day 1, one administration of 0.25 mg siponimod at day 2, one administration of 0.5 mg siponimod at day 3, one administration of 0.75 mg siponimod at day 4, one administration of 1.25 mg siponimod at day 5, and one administration of 2 mg siponimod at day 6. 23. The method of claim 11, wherein, in said initial titration regimen, immediate release dosage forms comprising 0.25 mg, 0.5 mg, 1 mg and 2 mg siponimod are used. 24. A method of treating multiple sclerosis in a patient receiving a chronic beta-blocker treatment and having a resting heart rate of >50 bpm under said chronic beta-blocker treatment comprising introducing in said patient a siponimod treatment by a) administering to said patient an initial titration regimen of siponimod comprising administering 0.25 mg siponimod at day 1, 0.25 mg of siponimod at day 2, 0.5 mg siponimod at day 3, 0.75 mg siponimod at day 4, 1.25 mg siponimod at day 5, and 2 mg siponimod at day 6; and b) administering to said patient 2 mg siponimod daily as a maintenance regimen. 25. The method of claim 24, wherein the multiple sclerosis is secondary progressive multiple sclerosis. 26. The method of claim 24, wherein the multiple sclerosis is relapsing-remitting multiple sclerosis. 27. The method of claim 24, wherein the maintenance regimen is administered once daily. 28. The method of claim 24, wherein the maintenance regimen is administered as an oral dosage form. 29. The method of claim 24, wherein the maintenance regimen is administered as an immediate release dosage form. 30. A method of treating multiple sclerosis in a patient receiving a chronic beta-blocker treatment and having a resting heart rate of ≤50 bpm under said chronic beta-blocker treatment comprising: a) interrupting said chronic beta-blocker treatment in said patient until the baseline heartrate is >50 bpm; b) initiating in said patient a siponimod treatment by b1) administering to said patient an initial titration regimen of siponimod comprising administering 0.25 mg siponimod at day 1, 0.25 mg of siponimod at day 2, 0.5 mg siponimod at day 3, 0.75 mg siponimod at day 4, 1.25 mg siponimod at day 5, and 2 mg siponimod at day 6; and b2) administering to said patient 2 mg siponimod daily as a maintenance regimen; and c) re-initiating in said patient a beta-blocker treatment the earliest at the first day when said patient is receiving the dosage of the maintenance regimen. 31. The method of claim 30, wherein the multiple sclerosis is secondary progressive multiple sclerosis. 32. The method of claim 30, wherein the multiple sclerosis is relapsing-remitting multiple sclerosis. 33. The method of claim 30, wherein the maintenance regimen is administered once daily. 34. The method of claim 30, wherein the maintenance regimen is administered as an oral dosage form. 35. The method of claim 30, wherein the maintenance regimen is administered as an immediate release dosage form. 36. The method of claim 30, wherein said initial titration regimen comprises one administration of 0.25 mg siponimod at day 1, one administration of 0.25 mg siponimod at day 2, one administration of 0.5 mg siponimod at day 3, one administration of 0.75 mg siponimod at day 4, one administration of 1.25 mg siponimod at day 5, and one administration of 2 mg siponimod at day 6.