METHODS FOR THE TREATMENT OF THYROID EYE DISEASE
Provided herein are methods of treating or reducing the severity of thyroid eye disease (TED), also known as thyroid-associated ophthalmopathy (TAO), or Graves' ophthalmopathy or orbitopathy (GO), as well as antibodies, or antigen binding fragments thereof, and pharmaceutical compositions comprising them, useful in the methods.
1 . A method of treating thyroid eye disease (TED) in a subject with TED, comprising administering to the subject a therapeutically effective amount of an antibody comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO:25, a HCDR2 comprising the amino acid sequence of SEQ ID NO:76, a HCDR3 comprising the amino acid sequence of SEQ ID NO:27, a LCDR1 comprising the amino acid sequence of SEQ ID NO:28, a LCDR2 comprising the amino acid sequence of SEQ ID NO:29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:30.
2 . The method of claim 1 , wherein the antibody comprises a heavy chain variable domain comprising SEQ ID NOs:31 or 78 or 79, and a light chain variable domain comprising SEQ ID NOs:32 or 80 or 81 or 82 or 83.
3 . The method of claim 2 , wherein the antibody comprises a heavy chain variable domain comprising SEQ ID NO:78 and a light chain variable domain comprising SEQ ID NOs:80 or 81 or 82 or 83.
4 . The method of claim 3 , wherein the antibody comprises the light chain variable domain comprising SEQ ID NO:80.
5 . The method of claim 3 , wherein the antibody comprises the light chain variable domain comprising SEQ ID NO:81.
6 . The method of claim 3 , wherein the antibody comprises the light chain variable domain comprising SEQ ID NO:82.
7 . The method of claim 3 , wherein the antibody comprises the light chain variable domain comprising SEQ ID NO:83.
8 . The method of claim 1 , wherein the therapeutically effective amount comprises a dosage of 1-60 mg/kg or 75-4500 mg IV Q3W; or 0.6-40 mg/kg or 45-3000 mg IV Q2W; or 0.3-20 mg/kg or 22-1500 mg IV QW.
9 . A method of reducing proptosis in a subject with thyroid eye disease (TED), comprising administering to the subject a therapeutically effective amount of antibody comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO:25, a HCDR2 comprising the amino acid sequence of SEQ ID NO:76, a HCDR3 comprising the amino acid sequence of SEQ ID NO:27, a LCDR1 comprising the amino acid sequence of SEQ ID NO:28, a LCDR2 comprising the amino acid sequence of SEQ ID NO:29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:30.
10 . The method of claim 9 , wherein the therapeutically effective amount comprises a dosage of 1-60 mg/kg or 75-4500 mg IV Q3W; or 0.6-40 mg/kg or 45-3000 mg IV Q2W; or 0.3-20 mg/kg or 22-1500 mg IV QW.
11 . The method of claim 9 , wherein proptosis is reduced by at least 2 mm.
12 . The method of claim 11 , wherein proptosis is reduced by at least 3 mm.
13 . The method of claim 12 , wherein proptosis is reduced by at least 4 mm.
14 . The method of claim 9 , wherein the method additionally comprises reducing the clinical activity score (CAS) in the subject with TED.
15 . The method of claim 14 , wherein CAS is reduced by at least 2 points.
16 . The method of claim 15 , wherein CAS is reduced by at least 3 points.
17 . The method of claim 14 , wherein proptosis is reduced by at least 3 mm and CAS is reduced by at least 3 points.
18 . A method of treating or reducing the severity of diplopia in a subject with thyroid eye disease (TED), comprising administering to the subject a therapeutically effective amount of antibody comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO:25, a HCDR2 comprising the amino acid sequence of SEQ ID NO:76, a HCDR3 comprising the amino acid sequence of SEQ ID NO:27, a LCDR1 comprising the amino acid sequence of SEQ ID NO:28, a LCDR2 comprising the amino acid sequence of SEQ ID NO:29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:30.
19 . The method of claim 18 , wherein the diplopia is constant diplopia.
20 . The method of claim 18 , wherein the diplopia is intermittent diplopia.
21 . The method of claim 18 , wherein the diplopia is inconstant diplopia.
22 . The method of claim 18 , wherein the improvement in or reduction in severity of diplopia is sustained at least 20 weeks after discontinuation of inhibitor administration.
23 . The method of any of claim 22 , wherein the improvement in or reduction in severity of diplopia is sustained at least 50 weeks after discontinuation of inhibitor administration.
24 . A method of reducing Clinical Activity Score (CAS) of thyroid eye disease (TED) in a subject with TED, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO:25, a HCDR2 comprising the amino acid sequence of SEQ ID NO:76, a HCDR3 comprising the amino acid sequence of SEQ ID NO:27, a LCDR1 comprising the amino acid sequence of SEQ ID NO:28, a LCDR2 comprising the amino acid sequence of SEQ ID NO:29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:30.
25 . The method of claim 1 , wherein the therapeutically effective amount comprises a dosage of 1-10 mg/kg.
26 . The method of claim 25 , wherein the therapeutically effective amount comprises a dosage of 1-5 mg/kg.
27 . The method of claim 26 , wherein the therapeutically effective amount comprises a dosage of about 2 mg/kg, about 3 mg/kg, about 4 mg/kg, or about 5 mg/kg.
28 . The method of claim 26 , wherein the therapeutically effective amount is administered every 1, 2, 3, 4, or 5 weeks (i.e., QW, Q2W, Q3W, Q4W, or Q5W).
29 . The method of claim 28 , wherein the therapeutically effective amount is administered intravenously (IV) or subcutaneously (SC).
30 . The method of claim 1 , wherein the therapeutically effective amount comprises a dosage of 1-5 mg/kg or 75-375 mg IV Q3W; or 0.6-4 mg/kg or 45-300 mg IV Q2W; or 0.3-3 mg/kg or 22-225 mg IV QW.