Dosage regimens for the treatment of autoimmune and inflammatory diseases using ly3871801
The administration of (S)-5-benzyl-N-(7-(3-hydroxy-3-methylbut-1-yn-1-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrophenyl[b][1,4]oxazon-3-yl)-1H-1,2,4-triazol-3-carboxamide addresses the inadequacies of existing treatments for autoimmune and inflammatory diseases, offering therapeutic efficacy.
Patent Information
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- ELI LILLY & CO
- Filing Date
- 2026-04-30
- Publication Date
- 2026-07-10
AI Technical Summary
Current treatments for autoimmune and inflammatory diseases are inadequate in effectively managing these conditions.
Administration of (S)-5-benzyl-N-(7-(3-hydroxy-3-methylbut-1-yn-1-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrophenyl[b][1,4]oxazon-3-yl)-1H-1,2,4-triazol-3-carboxamide or its pharmaceutically acceptable salt, in a dosage of 12.5 mg to 125 mg per dose, to treat autoimmune and inflammatory diseases.
The compound effectively treats autoimmune and inflammatory diseases by providing therapeutic benefits.
Smart Images
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Abstract
Description
Abstract of Dosing Regimen for Treating Autoimmune and Inflammatory Diseases Using LY3871801 This invention discloses a method for treating subjects with autoimmune or inflammatory diseases, and related formulations comprising administering to the patient a compound that is (S)-5-benzyl-N-(7-(3-hydroxy-3-methylbut-1-yn-1-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrophenyl[b][1,4]oxazon-3-yl)-1H-1,2,4-triazol-3-carboxamide, or a pharmaceutically acceptable salt thereof, wherein the dosage of the compound or a pharmaceutically acceptable salt thereof is about 12.5 mg to about 125 mg per dose (based on the free base equivalent of the compound).
Claims
WHAT IS CLAIMED IS:
1. A method of treating a patient having an autoimmune or inflammatory disease, comprising administering to the patient a compound of (5)-5-benzyl-7V-(7-(3-hydroxy-3- methylbut-l-yn-l-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[Z>][l,4]oxazepin-3-yl)-17 / -l,2,4- triazole-3 -carboxamide, or a pharmaceutically acceptable salt thereof, wherein the compound or the pharmaceutically acceptable salt is administered at a dose of about 12.5 mg to about 125 mg free base equivalent of said compound per dose.
2. The method of claim 1, wherein the autoimmune or inflammatory disease is a disease modulated by receptor-interacting protein (RIP) kinase 1.
3. The method of claim 1 or 2, wherein the autoimmune or inflammatory disease is selected from the group consisting of rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn's disease, cutaneous lupus erythematosus, lupus nephritis, systemic lupus erythematosus, and atopic dermatitis.
4. The method of any of claims 1-3, wherein the administering is carried out with an amorphous form of the compound.
5. The method of claim 4, wherein the amorphous form of the compound is part of a solid dispersion that comprises a polymer selected from the group consisting of hydroxypropyl methylcellulose acetate succinate (HPMC-AS), polyvinylpyrrolidone / vinyl acetate co-polymer, 6:4, Povidone K30, and hydroxypropyl methylcellulose (HPMC).
6. The method of any of claims 1-5, wherein the dose is about 12.5 mg, 18.75 mg, 25 mg, 31.25 mg, 37.5 mg, 43.75 mg, 50 mg, 56.25 mg, 62.5 mg, 68.75 mg, 75 mg, 81.25 mg, 87.5 mg, 93.75 mg, 100 mg, 106.25 mg, 112.5 mg, 118.75 mg, or 125 mg free base equivalent of said compound per dose.
7. The method of any of claims 1-5, wherein the dose is about 50 mg to about 75 mg free base equivalent of said compound per dose.
8. The method of any of claims 1-5, wherein the dose is about 25 mg to about 50 mg free base equivalent of said compound per dose.
9. The method of any of claims 1-5, wherein the dose is about 75 mg to about 100 mg free base equivalent of said compound per dose.
10. The method of any of claims 1-5, wherein the dose is about 100 mg to about 125 mg free base equivalent of said compound per dose.
11. The method of any of claims 1-10, wherein the maximum daily dose is about 25 mg, 50 mg, 75 mg, 100 mg, or 125 mg free base equivalent of said compound.
12. A method of treating a patient having an autoimmune or inflammatory disease, comprising administering to the patient an amorphous form of compound of (5)-5-benzyl-A-(7- (3-hydroxy-3-methylbut-l-yn-l-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[Z>][l,4]oxazepin- 3 -yl)- 17Z- 1 , 2, 4-triazole-3 -carboxamide, wherein the compound or the pharmaceutically acceptable salt is administered at a dose of about 12.5 mg to about 125 mg free base equivalent of said compound per dose, and wherein the dose is administered once per day.
13. The method of any of claims 1-12, wherein administering of the dose is via oral administration.
14. The method of any of claims 1-13, wherein the autoimmune or inflammatory disease is rheumatoid arthritis, psoriasis, or ulcerative colitis.
15. A method of treating a patient having rheumatoid arthritis, comprising administering to the patient an amorphous form of compound of (5)-5-benzyl-A-(7-(3-hydroxy-3-methylbut-l- yn-l-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[Z>][l,4]oxazepin-3-yl)-17 / -l,2,4-triazole-3- carboxamide, wherein the compound is administered at a dose of about 25 mg to about 125 mg per dose, once per day.
16. A method of treating a patient having psoriasis, comprising administering to the patient an amorphous form of compound of (5)-5-benzyl-A-(7-(3-hydroxy-3-methylbut-l-yn-l-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[A][ l ,4]oxazepin-3-yl)- IT / - l ,2,4-triazole-3-carboxamide, wherein the compound is administered at a dose of about 25 mg to about 125 mg per dose, once per day.
17. A method of treating a patient having ulcerative colitis, comprising administering to the patient an amorphous form of compound of (5)-5-benzyl-A-(7-(3-hydroxy-3-methylbut-l-yn-l- yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[Z>][l,4]oxazepin-3-yl)-l / 7-l,2,4-triazole-3- carboxamide, wherein the compound is administered at a dose of about 12.5 mg to about 125 mg per dose, once per day.
18. A pharmaceutical composition, comprising: a compound of (5)-5-benzyl-A-(7-(3-hydroxy-3-methylbut-l-yn-l-yl)-5-methyl-4-oxo-2.3.4.5-tetrahydrobenzo[Z>][l,4]oxazepin-3-yl)-l / 7-l,2,4-triazole-3-carboxamide in an amorphous form, and a polymer selected from the group consisting of hydroxypropyl methylcellulose acetate succinate (HPMC-AS), polyvinylpyrrolidone / vinyl acetate co-polymer, 6:4, Povidone K30, and hydroxypropyl methylcellulose (HPMC), wherein a weight ratio (w / w) of the compound to the polymer is about 1:4 to about 1.2:1.
19. The pharmaceutical composition of claim 18, wherein the polymer comprises hydroxypropyl methylcellulose acetate succinate (HPMC-AS).
20. The pharmaceutical composition of claim 19, wherein a weight ratio (w / w) of free base equivalent of the compound and the hydroxypropyl methylcellulose acetate succinate is about 1 :3 to about 1 : 1.
21. Compound (5)-5-benzyl-A-(7-(3-hydroxy-3-methylbut-l-yn-l-yl)-5-methyl-4-oxo-2.3.4.5-tetrahydrobenzo[Z>][l,4]oxazepin-3-yl)-17 / -l,2,4-triazole-3-carboxamide, for use in the treatment of an autoimmune or inflammatory disease in a patient, wherein the compound is administered at a dose of about 12.5 mg to about 125 mg free base equivalent of said compound per dose.
22. Compound (5)-5-benzyl-7V-(7-(3-hydroxy-3-methylbut-l-yn-l-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[Z>][l,4]oxazepin-3-yl)-U7-l,2,4-triazole-3-carboxamide, for use in the treatment of rheumatoid arthritis in a patient, wherein the compound is administered in an amorphous state at a dose of about 25 mg to about 125 mg free base equivalent of said compound per dose.
23. Compound (5)-5-benzyl-7V-(7-(3-hydroxy-3-methylbut-l-yn-l-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[Z>][l,4]oxazepin-3-yl)-U7-l,2,4-triazole-3-carboxamide, for use in the treatment of psoriasis in a patient, wherein the compound is administered in an amorphous state at a dose of about 25 mg to about 125 mg free base equivalent of said compound per dose.
24. Compound (5)-5-benzyl-7V-(7-(3-hydroxy-3-methylbut-l-yn-l-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[Z>][l,4]oxazepin-3-yl)-U7-l,2,4-triazole-3-carboxamide, for use in the treatment of ulcerative colitis in a patient, wherein the compound is administered in an amorphous state at a dose of about 12.5 mg to about 125 mg free base equivalent of said compound per dose.
25. Use of compound (5)-5-benzyl-7V-(7-(3-hydroxy-3-methylbut-l-yn-l-yl)-5-methyl-4- oxo-2, 3 ,4,5-tetrahydrobenzo[Z>] [ 1 ,4]oxazepin-3 -yl)- 1H- 1 ,2,4-triazole-3 -carboxamide or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treatment of an autoimmune or inflammatory disease in a patient, wherein the compound or the pharmaceutically acceptable salt is administered at a dose of about 12.5 mg to about 125 mg free base equivalent of said compound per dose.
26. Use of compound (5)-5-benzyl-7V-(7-(3-hydroxy-3-methylbut-l-yn-l-yl)-5-methyl-4- oxo-2, 3 ,4,5-tetrahydrobenzo[Z>] [ 1 ,4]oxazepin-3 -yl)- 1H- 1 ,2,4-triazole-3 -carboxamide, in the manufacture of a medicament for the treatment of an autoimmune or inflammatory disease in a patient, wherein the compound is administered at a dose of about 12.5 mg to about 125 mg free base equivalent of said compound per dose.
27. A pharmaceutical unit dosage composition, comprising about 12.5 mg to about 125 mg of a compound of (5)-5-benzyl-A-(7-(3-hydroxy-3-methylbut-l-yn-l-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[A][ l ,4]oxazepin-3-yl)- IT / - l ,2,4-triazole-3-carboxamide in an amorphous form, said unit dosage composition suitable for oral administration.
28. The pharmaceutical unit dosage composition of claim 27, comprising about 12.5 mg, 25 mg, 37.5 mg, 50 mg, 62.5 mg, or 75 mg of the compound.