Methods for reducing migraine frequency in a subject in need thereof
The present invention relates to methods for selecting a headache patient responsive to treatment with an anti-CGRP antibody and to methods for reducing headache frequency in the selected patient comprising administering an anti-CGRP antibody.
1. A method for reducing migraine frequency in a subject suffering from migraine comprising:
a) determining or having determined whether the subject exhibits allodynia and/or hyperalgesia during an interictal phase of a migraine, and
b) administering an anti-CGRP antagonist antibody or an anti-CGRP receptor antibody that blocks, inhibits, suppresses, or reduces the calcitonin gene related peptide (CGRP) pathway to the subject that does not exhibit signs of allodynia and/or hyperalgesia during the interictal phase of the migraine.
2. The method of claim 1 , wherein the subject suffers from episodic migraine.
3. The method of claim 1 , wherein the subject suffers from chronic migraine.
4. The method of claim 1 , wherein the subject is known to exhibit allodynia and/or hyperalgesia during an acute phase of the migraine.
5. The method of claim 1 , wherein the subject was determined during the interictal phase of the migraine to have a heat pain threshold of above 41° C. and/or a mechanical pain threshold of above 30 g for skin indentation with calibrated von Frey hairs.
6. The method of claim 1 , wherein the absence of allodynia and/or hyperalgesia during the interictal phase of the migraine was determined by quantitative sensory testing (QST).
7. The method of claim 1 , wherein the absence of allodynia and/or hyperalgesia during the interictal phase of the migraine was determined by questionnaire.
8. The method of claim 1 , wherein the anti-CGRP antagonist antibody or the anti-CGRP receptor antibody is a monoclonal antibody, a humanized antibody, or an antigen-binding fragment selected from a Fab, a Fab′, a F(ab′)2, an Fv, or an ScFv.
9. The method of claim 1 , wherein the anti-CGRP antagonist antibody comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO: 3; a CDR H2 amino acid sequence as set forth in SEQ ID NO: 4; a CDR H3 amino acid sequence as set forth in SEQ ID NO: 5; a CDR L1 amino acid sequence as set forth in SEQ ID NO: 6; a CDR L2 amino acid sequence as set forth in SEQ ID NO: 7; and a CDR L3 amino acid sequence as set forth in SEQ ID NO: 8.
10. The method of claim 9 , wherein:
the anti-CGRP antagonist antibody comprises a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 1, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:2; or
the anti-CGRP antagonist antibody comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO: 11, and a light chain comprising the amino acid sequence as set forth in SEQ ID NO: 12.
11. The method of claim 1 , wherein the anti-CGRP antagonist antibody comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO: 87; a CDR H2 amino acid sequence as set forth in SEQ ID NO: 88; a CDR H3 amino acid sequence as set forth in SEQ ID NO:89; a CDR L1 amino acid sequence as set forth in SEQ ID NO:84; a CDR L2 amino acid sequence as set forth in SEQ ID NO:85; and a CDR L3 amino acid sequence as set forth in SEQ ID NO:86.
12. The method of claim 11 , wherein:
the anti-CGRP antagonist antibody comprises a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 82, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 80; or
the anti-CGRP antagonist antibody comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO: 83, and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:81.
13. The method of claim 1 , wherein the anti-CGRP antagonist antibody comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO:93; a CDR H2 amino acid sequence as set forth in SEQ ID NO:94; a CDR H3 amino acid sequence as set forth in SEQ ID NO:95; a CDR L1 amino acid sequence as set forth in SEQ ID NO:91; a CDR L2 amino acid sequence as set forth in SEQ ID NO:92; and a CDR L3 amino acid sequence as set forth in SEQ ID NO:90.
14. The method of claim 13 , wherein:
the anti-CGRP antagonist antibody comprises a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 97, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 96; or
the anti-CGRP antagonist antibody comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:99, and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:98.
15. The method of claim 1 , wherein the anti-CGRP receptor antibody comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO: 103; a CDR H2 amino acid sequence as set forth in SEQ ID NO: 104; a CDR H3 amino acid sequence as set forth in SEQ ID NO: 105; a CDR L1 amino acid sequence as set forth in SEQ ID NO: 100; a CDR L2 amino acid sequence as set forth in SEQ ID NO: 101; and a CDR L3 amino acid sequence as set forth in SEQ ID NO: 102.
16. The method of claim 15 , wherein:
the anti-CGRP receptor antibody comprises a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 107, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 106; or
the anti-CGRP receptor antibody comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO: 109, and a light chain comprising the amino acid sequence as set forth in SEQ ID NO: 108.
17. The method of claim 1 , wherein the anti-CGRP antagonist antibody or the anti-CGRP receptor antibody is administered while the patient is migraine-free.
18. The method of claim 1 , wherein the allodynia is cutaneous allodynia.
19. A method for reducing migraine frequency in a subject suffering from migraine comprising:
a) determining or having determined whether said subject exhibits, or does not exhibit, allodynia and/or hyperalgesia during an interictal phase of a migraine, and
b) administering to said subject that does not exhibit signs of allodynia and/or hyperalgesia during the interictal phase of the migraine, an anti-CGRP antagonist antibody or an anti-CGRP receptor antibody that blocks, inhibits, suppresses, or reduces the calcitonin gene related peptide (CGRP) pathway.
20. A method of treating migraine in a subject comprising:
a) determining or having determined whether the subject exhibits allodynia and/or hyperalgesia during the interictal phase of a migraine, and
b) administering an anti-CGRP antagonist antibody or an anti-CGRP receptor antibody that blocks, inhibits, suppresses, or reduces the calcitonin gene related peptide (CGRP) pathway to the subject that does not exhibit signs of allodynia and/or hyperalgesia during the interictal phase of the migraine.