Methods for treating or preventing migraine headache
The present invention relates to methods of migraine prophylaxis using anti-CGRP receptor antibodies or binding fragments. In particular, methods for preventing or reducing the occurrence of migraine headache in a patient in need thereof comprising administering to the patient an anti-CGRP receptor or binding fragment according to specific dosage regimens are disclosed. Pharmaceutical compositions and administration devices comprising anti-CGRP receptor antibodies or binding fragments for use in the methods are also described.
1. A method for preventing or reducing the occurrence of migraine headache in a patient in need thereof comprising administering to the patient by subcutaneous injection once per month a dose of about 70 mg to about 140 mg of an anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody or antigen-binding fragment thereof, wherein the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof comprises a CDRH1 having the sequence of SEQ ID NO:14, a CDRH2 having the sequence of SEQ ID NO:23, a CDRH3 having the sequence of SEQ ID NO:34, a CDRL1 having the sequence of SEQ ID NO:44, a CDRL2 having the sequence of SEQ ID NO:55, and a CDRL3 having the sequence of SEQ ID NO:65.
2. The method of claim 1 , wherein the dose is 70 mg.
3. The method of claim 1 , wherein the dose is 140 mg.
4. The method of claim 3 , wherein the 140 mg dose is administered as two consecutive injections of 70 mg each.
5. The method of claim 1 , wherein the subcutaneous injection is delivered to the patient with a syringe pre-filled with a pharmaceutical composition comprising the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof.
6. The method of claim 1 , wherein the subcutaneous injection is delivered to the patient with an autoinjector.
7. The method of claim 1 , wherein the number of monthly migraine headache days experienced by the patient is reduced following administration of the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof as compared to the number of monthly migraine headache days experienced by a patient not receiving the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof.
8. The method of claim 1 , wherein the number of monthly migraine headache hours experienced by the patient is reduced following administration of the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof as compared to the number of monthly migraine headache hours experienced by a patient not receiving the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof.
9. The method of claim 1 , wherein the number of monthly migraine-specific medication use days experienced by the patient is reduced following administration of the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof as compared to the number of monthly migraine-specific medication use days experienced by a patient not receiving the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof.
10. The method of claim 1 , wherein administration of the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof does not substantially cause an adverse side effect in the patient.
11. The method of claim 1 , wherein the patient has or is diagnosed with episodic migraine.
12. The method of claim 1 , wherein the patient has or is diagnosed with chronic migraine.
13. The method of claim 1 , wherein the patient has not previously received prophylactic therapy for migraine headaches.
14. The method of claim 1 , wherein the patient has failed or is intolerant to at least one other migraine headache prophylactic therapy.
15. The method of claim 14 , wherein the other migraine headache prophylactic therapy is an antiepileptic, a tricyclic antidepressant, or a beta-blocker.
16. The method of claim 1 , wherein the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof specifically binds to the human CGRP receptor with a K D ≤100 nM.
17. The method of claim 1 , wherein the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable region (V H ) comprising the sequence of SEQ ID NO:92, and a light chain variable region (V L ) comprising the sequence of SEQ ID NO:80.
18. The method of claim 1 , wherein the anti-CGRP receptor monoclonal antibody comprises a heavy chain comprising the sequence of SEQ ID NO:105, and a light chain comprising the sequence of SEQ ID NO:123.
19. The method of claim 1 , wherein the anti-CGRP receptor monoclonal antibody is a monoclonal IgG1 or monoclonal IgG2 antibody.
20. The method of claim 1 , wherein the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof is administered in a pharmaceutical composition comprising a buffer, a surfactant, and a stabilizing agent.
21. The method of claim 20 , wherein the buffer is an acetate buffer.
22. The method of claim 20 , wherein the surfactant is polysorbate 20 or polysorbate 80.
23. The method of claim 20 , wherein the stabilizing agent is sucrose.
24. The method of claim 1 , wherein the dose is administered as a single subcutaneous injection in a volume of about 1 mL or less.
25. A method for prophylactically treating a patient for migraine comprising administering to the patient by subcutaneous injection once per month a dose of about 70 mg to about 140 mg of an anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof, wherein the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof comprises a CDRH1 having the sequence of SEQ ID NO:14, a CDRH2 having the sequence of SEQ ID NO:23, a CDRH3 having the sequence of SEQ ID NO:34, a CDRL1 having the sequence of SEQ ID NO:44, a CDRL2 having the sequence of SEQ ID NO:55, and a CDRL3 having the sequence of SEQ ID NO:65.
26. The method of claim 25 , wherein the dose is 70 mg.
27. The method of claim 25 , wherein the dose is 140 mg.
28. The method of claim 27 , wherein the 140 mg dose is administered as two consecutive injections of 70 mg each.
29. The method of claim 25 , wherein the subcutaneous injection is delivered to the patient with a syringe pre-filled with a pharmaceutical composition comprising the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof.
30. The method of claim 25 , wherein the subcutaneous injection is delivered to the patient with an autoinjector.
31. The method of claim 25 , wherein the number of monthly migraine headache days experienced by the patient is reduced following administration of the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof as compared to the number of monthly migraine headache days experienced by a patient not receiving the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof.
32. The method of claim 25 , wherein the number of monthly migraine headache hours experienced by the patient is reduced following administration of the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof as compared to the number of monthly migraine headache hours experienced by a patient not receiving the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof.
33. The method of claim 25 , wherein the number of monthly migraine-specific medication use days experienced by the patient is reduced following administration of the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof as compared to the number of monthly migraine-specific medication use days experienced by a patient not receiving the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof.
34. The method of claim 25 , wherein administration of the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof does not substantially cause an adverse side effect in the patient.
35. The method of claim 25 , wherein the migraine is episodic migraine.
36. The method of claim 25 , wherein the migraine is chronic migraine.
37. The method of claim 25 , wherein the patient has not previously received prophylactic therapy for migraine headaches.
38. The method of claim 25 , wherein the patient has failed or is intolerant to at least one other migraine headache prophylactic therapy.
39. The method of claim 38 , wherein the other migraine headache prophylactic therapy is an antiepileptic, a tricyclic antidepressant, or a beta-blocker.
40. The method of claim 25 , wherein the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof specifically binds to the human CGRP receptor with a K D ≤100 nM.
41. The method of claim 25 , wherein the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable region (V H ) comprising the sequence of SEQ ID NO:92, and a light chain variable region (V L ) comprising the sequence of SEQ ID NO:80.
42. The method of claim 25 , wherein the anti-CGRP receptor monoclonal antibody comprises a heavy chain comprising the sequence of SEQ ID NO:105, and a light chain comprising the sequence of SEQ ID NO:123.
43. The method of claim 25 , wherein the anti-CGRP receptor monoclonal antibody is a monoclonal IgG1 or monoclonal IgG2 antibody.
44. The method of claim 25 , wherein the anti-CGRP receptor monoclonal antibody or antigen-binding fragment thereof is administered in a pharmaceutical composition comprising a buffer, a surfactant, and a stabilizing agent.
45. The method of claim 44 , wherein the buffer is an acetate buffer.
46. The method of claim 44 , wherein the surfactant is polysorbate 20 or polysorbate 80.
47. The method of claim 44 , wherein the stabilizing agent is sucrose.
48. The method of claim 25 , wherein the dose is administered as a single subcutaneous injection in a volume of about 1 mL or less.
49. A method for preventing or reducing the occurrence of migraine headache in a patient in need thereof comprising administering to the patient by subcutaneous injection a dose of 70 mg or 140 mg of an anti-CGRP receptor monoclonal antibody once per month, wherein the anti-CGRP receptor monoclonal antibody comprises a CDRH1 having the sequence of SEQ ID NO:14, a CDRH2 having the sequence of SEQ ID NO:23, a CDRH3 having the sequence of SEQ ID NO:34, a CDRL1 having the sequence of SEQ ID NO:44, a CDRL2 having the sequence of SEQ ID NO:55, and a CDRL3 having the sequence of SEQ ID NO:65, and wherein the dose is administered as a single subcutaneous injection in a volume of about 1 mL or less.
50. The method of claim 49 , wherein the dose is 70 mg.
51. The method of claim 49 , wherein the dose is 140 mg.
52. The method of claim 49 , wherein the anti-CGRP receptor monoclonal antibody comprises a heavy chain variable region (V H ) comprising the sequence of SEQ ID NO:92, and a light chain variable region (V L ) comprising the sequence of SEQ ID NO:80.
53. The method of claim 49 , wherein the anti-CGRP receptor monoclonal antibody comprises a heavy chain comprising the sequence of SEQ ID NO:105, and a light chain comprising the sequence of SEQ ID NO:123.
54. A method for prophylactically treating a patient for migraine comprising administering to the patient by subcutaneous injection a dose of 70 mg or 140 mg of an anti-CGRP receptor monoclonal antibody once per month, wherein the anti-CGRP receptor monoclonal antibody comprises a CDRH1 having the sequence of SEQ ID NO:14, a CDRH2 having the sequence of SEQ ID NO:23, a CDRH3 having the sequence of SEQ ID NO:34, a CDRL1 having the sequence of SEQ ID NO:44, a CDRL2 having the sequence of SEQ ID NO:55, and a CDRL3 having the sequence of SEQ ID NO:65, and wherein the dose is administered as a single subcutaneous injection in a volume of about 1 mL or less.
55. The method of claim 54 , wherein the dose is 70 mg.
56. The method of claim 54 , wherein the dose is 140 mg.
57. The method of claim 54 , wherein the anti-CGRP receptor monoclonal antibody comprises a heavy chain variable region (V H ) comprising the sequence of SEQ ID NO:92, and a light chain variable region (V L ) comprising the sequence of SEQ ID NO:80.
58. The method of claim 54 , wherein the anti-CGRP receptor monoclonal antibody comprises a heavy chain comprising the sequence of SEQ ID NO:105, and a light chain comprising the sequence of SEQ ID NO:123.