Method of treating Crohn's disease by administering a triple combination therapy of anti-integrin antibody, adalimumab and methotrexate

12246,064

17/152585

January 19, 2021

The invention features new a method for treating inflammatory bowel disease, including Crohn's Disease (CD) or ulcerative colitis in a human patient, comprising administering to a patient a combination therapy comprising an anti-α4β7 antibody, a TNFα antagonist, and an immunomodulator.

Millennium Pharmaceuticals, Inc. (Cambridge, MA, US); Icahn School of Medicine at Mount Sinai (New York, NY, US)

Takeda Pharmaceutical Company Limited (Osaka, JP)

1. A method of treating Crohn's Disease (CD) in a patient, wherein the method comprises the step of: administering to a human patient identified as a high-risk CD patient, a triple combination therapy comprising a humanized anti-α4β7 antibody, adalimumab, and methotrexate, wherein the triple combination therapy is administered to the patient according to the following dosing regimen: a. an initial dose of 155 to 180 mg of humanized anti-α4β7 antibody as an intravenous infusion, followed by a second subsequent dose of 155 to 180 mg of humanized anti-α4β7 antibody as an intravenous infusion at about two weeks after the initial dose; followed by a third subsequent dose of 155 to 180 mg of the humanized anti-α4β7 antibody as an intravenous infusion at about six weeks after the initial dose; b. an initial dose of 160 mg of adalimumab as a subcutaneous injection, followed by a second subsequent dose of 80 mg of adalimumab as a subcutaneous injection, followed by a third subsequent dose of 40 mg of adalimumab at about four weeks after the initial dose; and c. an initial dose of 15 mg of methotrexate; further wherein the anti-α4β7 antibody comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin, wherein the humanized antibody has binding specificity for the α4β7 complex, wherein the antigen-binding region comprises the CDRs: Light chain: CDR1 SEQ ID NO:7 CDR2 SEQ ID NO:8 and CDR3 SEQ ID NO:9; and Heavy chain: CDR1 SEQ ID NO:4 CDR2 SEQ ID NO:5 and CDR3 SEQ ID NO:6.

2. The method of claim 1 , wherein the humanized anti-α4β7 antibody has a heavy chain variable region sequence of amino acids 20 to 140 of SEQ ID NO: 1 and/or a light chain variable region sequence of amino acids 20 to 131 of SEQ ID NO:2.

3. The method of claim 1 , wherein the humanized anti-α4β7 antibody has a heavy chain comprising amino acids 20 to 470 of SEQ ID NO:1 and a light chain comprising amino acids 20 to 238 of SEQ ID NO:2.

4. The method of claim 1 , wherein the anti-α4β7 antibody is vedolizumab.

5. The method of claim 1 , wherein the high-risk CD patient additionally is administered a dose of corticosteroid.

6. A method of treating Crohn's Disease in a patient, comprising administering to the patient vedolizumab, adalimumab, and methotrexate according to a triple combination therapy, wherein the triple combination therapy comprises administering vedolizumab at a dose of 155 to 180 mg at weeks 0, 2, and 6, followed by administration every 8 weeks thereafter; subcutaneously administering a 160 mg dose of adalimumab at week 0, an 80 mg dose of adalimumab at week 2, and a 40 mg dose of adalimumab at week 4 and every two weeks thereafter; and administering 15 mg methotrexate; wherein the patient is at high risk of complication from the Crohn's disease.

7. The method of claim 6 , wherein adalimumab is discontinued at week 26.

8. The method of claim 6 , wherein the methotrexate is administered orally.

9. The method of claim 6 , wherein the methotrexate is discontinued at week 34.

10. The method of claim 6 , wherein the patient is a high-risk Crohn's disease patient.

11. A method of treating Crohn's Disease in a patient, comprising administering to the patient vedolizumab, infliximab, and methotrexate according to a triple combination therapy, wherein the triple combination therapy comprises administering vedolizumab at a dose of 155 to 180 mg at weeks 0, 2, and 6, followed by administration every 8 weeks thereafter; intravenously administering infliximab at a dose of 5 mg/kg at weeks 0, 2 and 6, and then every 8 weeks thereafter; and administering 15 mg methotrexate; wherein the patient is at high risk of complication from the Crohn's disease.

12. The method of claim 11 , wherein infliximab is discontinued at week 26.

13. The method of claim 11 , wherein the methotrexate is administered orally.

14. The method of claim 11 , wherein the methotrexate is discontinued at week 34.

15. The method of claim 11 , wherein vedolizumab is administered at a dose of 155 to 170 mg.

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