Treatment of Crohn's disease with laquinimod

• US 20110027219A1
• Filed: 07/29/2010
• Published: 02/03/2011
• Est. Priority Date: 07/30/2009
• Status: Active Grant

• Current Assignee: Active Biotech AB
• Original Assignee: Teva Pharmaceutical Industries Limited
• Inventors: Kaye, Joel, Haviv, Asi, Blaugrund, Eran, Tarcic, Nora
• Granted Patent: US 8,598,203 B2
• Time in Patent Office: Days
• US Class Current: 424/85.1
• CPC Class Codes: A61K 31/4704 2-Quinolinones, e.g. carbostyril
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/606 having amino groups
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07D 215/56 with oxygen atoms in position 4

Abstract

This application provides for a method of treating a subject suffering from Crohn'"'"'s disease, the method comprising periodically administering to the subject an amount of laquinimod or pharmaceutically acceptable salt thereof effective to treat the subject. This application provides for use of laquinimod in the manufacture of a medicament for treating a subject suffering from Crohn'"'"'s disease. This application also provides for a pharmaceutical composition comprising laquinimod for use in treating a subject suffering from Crohn'"'"'s disease.

Claims

1. A method of treating a subject suffering from Crohn'"'"'s disease, the method comprising periodically administering to the subject an amount of laquinimod or pharmaceutically acceptable salt thereof effective to treat the subject.

2. The method of claim 1, wherein the amount of laquinimod is effective to reduce a symptom of Crohn'"'"'s disease in the subject, induce clinical response, induce or maintain clinical remission, inhibit disease progression, or inhibit a disease complication in the subject.

3. The method of claim 1, wherein the amount of laquinimod is effective to reduce the Crohn'"'"'s Disease Activity Index score of the subject, lower the C-Reactive Protein level of the subject, lower the fecal calprotein level of the subject, or reduce the number of open draining fistulas in the subject.

4. The method of claim 3, wherein the Crohn'"'"'s Disease Activity Index score of the subject is reduced by at least 100 points.

5. The method of claim 3, wherein the Crohn'"'"'s Disease Activity Index score of the subject is reduced to under 150.

6. The method of any one of claim 3, wherein the number of open draining fistulas in the subject is decreased at least 50% as compared to prior to initiation of the periodic administration.

7. The method of claim 1, wherein the periodic administration is oral.

8. The method of claim 1, wherein the amount is administered by a unit dose of 0.5 mg of laquinimod.

9. The method of claim 1, wherein the periodic administration is daily administration.

10. The method of claim 9, wherein the amount of laquinimod is 0.5-2.0 mg/day.

11. The method of claim 10, wherein the amount of laquinimod is 1.0 mg/day.

12. The method of claim 10, wherein the amount of laquinimod is 1.5 mg/day.

13. The method of claim 10, wherein the amount of laquinimod is 2.0 mg/day.

14. The method of claim 1, wherein a loading dose of an amount different from the intended dose is administered for a period of time at the start of the periodic administration.

15. The method of claim 14, wherein the loading dose is double the amount of the intended dose.

16. The method of claim 14, wherein the loading is administered for two days at the start of the periodic administration.

17. The method of claim 1, wherein the subject had active moderate to severe Crohn'"'"'s disease prior to the administration of laquinimod.

18. The method of claim 1, wherein the subject had a Crohn'"'"'s Disease Activity Index score of 220-450 prior to the administration of laquinimod.

19. The method of any one of claim 1, wherein the subject had a C-Reactive Protein level of above 5 mg/L prior to the administration of laquinimod.

20. The method of claim 17, wherein diagnosis of the subject prior to administration excluded Indeterminate Colitis.

21. The method of claim 17, wherein diagnosis of the subject prior to administration excluded Ulcerative Colitis.

22. The method of claim 1, wherein the periodic administration continues for 8 weeks or more.

23. The method of claim 1, wherein the laquinimod is in the form of laquinimod sodium.

24. The method of claim 1, wherein the subject is a human.

25. The method of claim 1, further comprising administration of 5-aminosalicylic acid, antibiotics, corticosteroids, immunosuppressors, TNFα

agents or anti-integrins.

26-27. -27. (canceled)