TREATMENT OF PEMPHIGUS

• US 20180050027A1
• Filed: 12/18/2015
• Published: 02/22/2018
• Est. Priority Date: 12/18/2014
• Status: Active Grant

• Current Assignee: Principia Biopharma Inc. (Sanofi )
• Original Assignee: Principia Biopharma Inc. (Sanofi )
• Inventors: GOURLAY, Steven
• Granted Patent: US 10,485,797 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present disclosure provides methods of treating with a BTK inhibitor a blistering disease, in particular pemphigus vulgaris or pemphigus folliaceous in a mammal, use of a BTK inhibitor as a replacement therapy for corticosteroid therapy for diseases treatable with a corticosteroid, such as autoimmune or inflammatory disease and in particular where corticosteroids are used as first or second line therapy, and pharmaceutical formulations comprising the same.

Claims

1. A method of treating an acute inflammatory and/or autoimmune disease in a mammal in need thereof where corticosteroid therapy is used as the first or second line therapy comprising administering to said mammal in need of said treatment a therapeutically effective amount of a BTK inhibitor in place of or in combination with said corticosteroid therapy;

and

optionally administering said BTK inhibitor in combination with a noncorticosteroidal immunosupressive or antiinflammatory agent.

5. The method of any one of claims 1 to 4 wherein the autoimmune and/or inflammatory disease is chosen from Table 1 or 2 below:

6. The method of any one of claims 1 to 5 wherein the disease is phemphigus vulgaris.

7. The method of any one of claims 1 to 4 wherein the BTK inhibitor is administered as a monotherapy.

8. The method of any one of claims 1 to 5 wherein the BTK inhibitor is administered in combination with a noncorticosteroidal anti-inflammatory and/or immunosuppressive agent.

9. The method of any one of claims 1 to 8 wherein the noncorticosteroidal anti-inflammatory and/or immunosuppressive agent is anti-CD20 antibody, anti-TNF antibody, anti-IL6 agent, anti-IL17 agent, or abatacept.

10. The method of any one of claims 1 to 8 wherein the noncorticosteroidal agent is rituximab, tositumomab, veltuzumab, obinutuzumab, Enbrel, or ofatumumab, or a biosimilar version thereof.

11. The method of any one of claims 1-10 wherein the BTK inhibitor is chosen from

(R,E)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]-pyrimidin-1-yl)piperidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile,

N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)-pyrimidin-4-yl)amino)phenyl)acrylamide,

Ibrutinib (pharmacyclics),

AVL 263 and 293 (Avila Therapeutics, Celgene Corporation),

GDC-0834 (Genentech),

GDC0853 (Genentech),

BMS-488516 and 509744 (Bristol Myers Squibb),

CGI-1746 (Gilead Sciences),

CTA-056 (Genentech),

HY-11066 (also CTK417891),

ONO-4059 (Ono Pharmaceutical Co. Ltd), ONO-WG37 (Ono Pharmaceutical Co. Ltd),

PLS-123 (Peking Univ.),

RN486 (Hoffmann Las Roche),

HM71224 (Hanmi Pharmceutical Co. Ltd.), and

ACP-196 (also Acalabrutinib, Acerta Pharma BV).

12. The method of any one of claims 1-10 wherein the BTK inhibitor is chosen from

ABT-105 or ABBV-105 (AbbVie),

AC0025 (ACEA Biosciences),

BGB3111 (BeiGene), CC-292 (Celgene),

EBI-1266 (Eternity Bioscience),

MSC-2364447 (Merck Biopharma),

PF-06250112 and PF-303 (Pfizer),

RG7625 and RG7880 (Hoffmann La Roche),

SNS-062 (Sunesis), TP-4207 (Tolero Pharmaceuticals), and

X-022 (X-Chem).

13. The method of any one of claims 1-10 wherein the BTK inhibitor is chosen from

(R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one,

(R)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide,

(S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide,

(S)-7-(1-(but-2-ynoyl)piperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide,

N-(3-((2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[3,2-d]pyrimidin-4-yl)oxy)phenyl)acrylamide,

1-(3-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)oxy)phenyl)prop-2-en-1-one,

(R)-6-amino-9-(1-(but-2-ynoyl)pyrrolidin-3-yl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one,

N-(2-((6-((5-(5-fluoro-2-(hydroxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]pyridazin-3(4H)-yl)phenyl)-1-methyl-2-oxo-1,2-dihydropyridin-3-yl)amino)pyridin-2-yl)amino)ethyl)acrylamide,

N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide,

(S)-5-amino-1-(1-cyanopiperidin-3-yl)-3-(4-(2,4-difluorophenoxy)phenyl)-1H-pyrazole-4-carboxamide,

6-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)nicotinamide, and

(R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(5-chlorobenzo[d]oxazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide.

14. The method of any one of claims 1-10 wherein the BTK inhibitor is chosen from

15. The method of any one of claims 1-13 wherein the BTK inhibitor is administered in a pharmaceutical composition.

2. A method of treating an inflammatory and/or autoimmune disease in a mammal in need thereof where corticosteroid therapy is used as the first or second line maintenance therapy comprising administering to said mammal in need of said treatment a therapeutically effective amount of a BTK inhibitor in place of or in combination with said corticosteroid therapy;

and

optionally administering said BTK inhibitor in combination with a noncorticosteroidal immunosupressive or antiinflammatory agent.

3. A method of eliminating or reducing therapeutic dose of corticosteroid used in the treatment of an inflammatory and/or autoimmune disease in a mammal in need thereof where corticosteroid therapy is used as the first or second line in chronic maintenance therapy comprising administering to said mammal in need of said treatment a therapeutically effective amount of a BTK inhibitor in place of or in combination with said corticosteroid therapy;

and

optionally administering said BTK inhibitor in combination with a noncorticosteroidal immunosupressive or antiinflammatory agent.

4. A method of treating an autoimmune and/or inflammatory disease in a mammal in need thereof which method comprises administering to the mammal in need of said treatment a therapeutically effective amount of a BTK inhibitor for a treatment period sufficient to treat acute flares of the autoimmune diseases.