METHODS OF TREATING A BRUTON'S TYROSINE KINASE DISEASE OR DISORDER
The present invention provides methods of treating, stabilizing or lessening the severity or progression of a disease or disorder associated with Bruton's tyrosine kinase (BTK) TEC and interleukin-2-inducible T-cell kinase (ITK).
1 . A method of preventing, treating, stabilizing or lessening the severity or progression of an autoimmune disorder, the method comprising administering to a patient in need thereof a pharmaceutically acceptable composition comprising a therapeutically effective amount of N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (1):
or a pharmaceutically acceptable salt thereof.
2 . The method according to claim 1 , wherein the therapeutically effective amount of Compound 1 is about 125 mg BID to about 750 mg BID.
3 . The method according to claim 1 , wherein the therapeutically effective amount of Compound 1 is about 125 mg to about 375 mg.
4 . The method according to any of claims 1 - 3 , wherein the autoimmune disorder is selected from lupus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, mixed connective tissue disease, celiac disease, inflammatory myopathy, diabetes mellitus type 1, and Lambert-Eaton myasthenic syndrome.
5 . The method according to claim 4 , wherein the autoimmune disorder is lupus.
6 . The method according to claim 5 , wherein the lupus is systemic lupus erythematosis (SLE).
7 . The method according to claim 5 , wherein the lupus is drug-induced lupus erythematosus.
8 . The method according to any of claims 1 - 7 , wherein the pharmaceutically acceptable composition is formulated as an oral dosage form.
9 . The method according to claim 1 , wherein the pharmaceutically acceptable composition is administered twice a day.
10 . The method according to any of claims 1 - 9 , wherein the pharmaceutically acceptable composition is administered for at least one 28-day cycle.
11 . The method according to any of claims 1 - 10 , wherein Compound 1 is administered as a salt.
12 . The method according to claim 11 , wherein the salt is a benzenesulfonic acid salt.
13 . The method according to claim 12 , wherein the composition comprises from about 10% to about 50% N-(3 -(5 -fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide besylate.
14 . The method according to claim 13 , wherein the composition comprises about 42% N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide besylate.
15 . The method according to claim 13 or claim 14 , wherein the composition comprises from about 5% to about 15% by weight of wetting agent.
16 . The method according to claim 15 , wherein the composition comprises about 10% by weight of wetting agent.
17 . The method according to claim 15 or 16 , wherein the wetting agent is selected from poloxamer, polyoxyethylene ethers, polyoxyethylene sorbitan fatty acid esters polyoxyethylene fatty acid esters, polyethylene glycol fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, polysorbates, cetyl alcohol, glycerol fatty acid esters, polyoxymethylene stearate, sodium lauryl sulfate, sorbitan fatty acid esters, sucrose fatty acid esters, benzalkonium chloride, polyethoxylated castor oil, and docusate sodium.
18 . The method according to claim 17 , wherein the wetting agent is a poloxamer.
19 . The method according to claim 18 , wherein the poloxamer is poloxamer 407.
20 . The method according to any of claims 1 - 19 , wherein the therapeutically effective amount is about 125 mg BID.
21 . The method according to any of claims 1 - 19 , wherein the therapeutically effective amount is about 250 mg BID.