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EP-4739391-A1 - METHODS OF TREATING CHRONIC THYROID EYE DISEASE

EP4739391A1EP 4739391 A1EP4739391 A1EP 4739391A1EP-4739391-A1

Abstract

Methods of treating patients with chronic thyroid eye disease are provided for herein, such as by administering antibodies and compositions that bind to and/or antagonize IGF-1R.

Inventors

  • CIULLA, Thomas

Assignees

  • Viridian Therapeutics, Inc.

Dates

Publication Date
20260513
Application Date
20240703

Claims (20)

  1. 1. A method of treating a patient suffering from chronic thyroid eye disease (TED), the method comprising administering a pharmaceutical composition comprising an anti-IGF-lR antibody at a therapeutically effective dosing regimen, wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 7, a HCDR2 of SEQ ID NO: 8, and a HCDR3 of SEQ ID NO: 9 and the light chain comprises a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5 and a LCDR3 of SEQ ID NO: 6.
  2. 2. A method of treating a patient suffering from thyroid eye disease (TED), the method comprising administering a pharmaceutical composition comprising an anti-IGF-lR antibody at a therapeutically effective dosing regimen, wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 7, a HCDR2 of SEQ ID NO: 8, and a HCDR3 of SEQ ID NO: 9 and the light chain comprises a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5 and a LCDR3 of SEQ ID NO: 6, wherein the patient, prior to treatment, has had one or more symptoms of thyroid eye disease for at least 12 months.
  3. 3. The method of claim 1, wherein the patient, prior to treatment, has had one or more symptoms of thyroid eye disease for at least 12 months.
  4. 4. The method of any one of the preceding claims, wherein the patient suffers one or more symptoms of TED selected from the group consisting of lid retraction greater than 2 mm, exophthalmos (proptosis) of greater than or equal to 3 mm, Clinical Activity Score (CAS) from about 0 to about 7, and inconstant or constant diplopia.
  5. 5. The method of claim 4, wherein the exophthalmos is greater than or equal to 3 mm above the normal range for their race and gender.
  6. 6. The method of any one of the preceding claims, wherein the patient, prior to treatment, had a CAS of or greater than 0, 1, 2, 3, or 4.
  7. 7. The method of any one of the preceding claims, wherein the patient, prior to treatment, had a CAS of greater than 2.
  8. 8. The method of any one of claims 1-6, wherein the patient, prior to treatment, had a CAS less than 2.
  9. 9. The method of any one of claims 1-7, wherein the patient, prior to treatment, had a CAS of 2-4.
  10. 10. The method of any one of the preceding claims, wherein the patient, prior to treatment, has had one or more symptoms of thyroid eye disease for at least 15 months.
  11. 11. A method of treating a patient suffering from inactive thyroid eye disease (TED), the method comprising administering a pharmaceutical composition comprising an anti-IGF-lR antibody at a therapeutically effective dosing regimen, wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 7, a HCDR2 of SEQ ID NO: 8, and a HCDR3 of SEQ ID NO: 9 and the light chain comprises a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5 and a LCDR3 of SEQ ID NO: 6.
  12. 12. A method of treating a patient suffering from thyroid eye disease (TED), the method comprising administering a pharmaceutical composition comprising an anti-IGF-lR antibody at a therapeutically effective dosing regimen, wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 7, a HCDR2 of SEQ ID NO: 8, and a HCDR3 of SEQ ID NO: 9 and the light chain comprises a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5 and a LCDR3 of SEQ ID NO: 6, wherein the patient, prior to treatment, had a Clinical Activity Score (CAS) of 2 or less.
  13. 13. The method of any one of the preceding claims, wherein the patient exhibits fibrosis.
  14. 14. A method of treating fibrosis associated with thyroid eye disease (TED), the method comprising administering to a patient in need of treatment an anti-IGF-lR antibody at a therapeutically effective dosing regimen, wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 7, a HCDR2 of SEQ ID NO: 8, and a HCDR3 of SEQ ID NO: 9 and the light chain comprises a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5 and a LCDR3 of SEQ ID NO: 6.
  15. 15. The method of any one of claims 11-14, wherein the patient, prior to treatment, had a Clinical Activity Score (CAS) of 0 or 1.
  16. 16. The method of any one of claims 11-15, wherein the patient has one or more symptoms of TED selected from the group consisting of lid retraction greater than 2 mm, exophthalmos (proptosis) of greater than or equal to 3 mm above the normal range for their race and gender, and inconstant or constant diplopia.
  17. 17. The method of any one of the preceding claims, wherein the patient, prior to treatment, has had one or more symptoms of thyroid eye disease for at least 2 years.
  18. 18. The method of any one of the preceding claims, wherein the therapeutically effective dosing regimen comprises administering to the patient a first dose of 3.0 mg/kg to 20 mg/kg.
  19. 19. The method of claim 18, wherein the first dose is 3.0 mg/kg, 5.0 mg/kg, 10 mg/kg, or 20 mg/kg.
  20. 20. The method of any one of the preceding claims, wherein the therapeutically effective dosing regimen comprises administering to the patient a subsequent dose.

Description

METHODS OF TREATING CHRONIC THYROID EYE DISEASE CROSS REFERENCE TO RELATED APPLICATIONS [0001] The present application claims benefit of U.S. Provisional Patent Application No. 63/512,468, filed on July 7, 2023, which is hereby incorporated by reference in its entirety. SEQUENCE LISTING [0002] The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on July 3, 2024, is named VRD-016WOl_SL and is 41,045 bytes. BACKGROUND [0003] Thyroid Eye Disease (TED) is an autoimmune condition most commonly associated with Graves’ disease and hyperthyroidism but can also be found in patients who are euthyroid or hypothyroid. The disease course has historically been said to transition from a first active and progressive phase (“active TED”), which is characterized by inflammation of orbital and external periorbital tissues, to a more stabilized and fibrotic phase. Active TED can be characterized by local inflammation of conjunctivae, superficial vasculature, orbital fat, lids, and extraocular muscles. The second phase of TED can be characterized by a dampened autoimmune inflammation of the first phase, leaving sequelae of expanded, fibrotic orbital tissues and dysfunctional, tethered extraocular muscles, though evidence exists that these TED patients may also exhibit an underlying inflammatory component. Accordingly, the onset of this non-active phase may be indicated by the duration, severity, and/or nature of disease symptoms. In view of the different natures of the two disease phases, there remains a need for effective therapies for TED. SUMMARY [0004] The disclosure relates generally to IGF-1R antibodies, and antigen binding fragments thereof, including any forms, variants, or derivatives thereof, and uses thereof. Certain IGF-1R antibodies and antigen-binding fragments inhibit IGF-1R function or block the biological functions of IGF-I mediated IGF-1R signaling. Additionally, the invention generally relates to methods for treating thyroid-associated ophthalmopathy (TAO), also known as thyroid eye disease (TED), Graves’ ophthalmopathy or orbitopathy (GO), thyrotoxic exophthalmos, dysthyroid ophthalmopathy, autoimmune associated eye disorders associated with IGF-1R signaling, inflammatory orbital disorder associated with IGF-1R signaling, and other thyroid eye disorders associated with IGF-1R signaling, including chronic TED. [0005] In one aspect, the invention features a method of treating a patient suffering from chronic thyroid eye disease (TED), the method comprising administering a pharmaceutical composition comprising an anti-IGF-lR antibody, wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1, a HCDR2, and a HCDR3 of SEQ ID NO: 10 and the light chain comprises a LCDR1, a LCDR2, and a LCDR3 of SEQ ID NO: 11. In some embodiments, the anti-IGF-lR antibody is administered at a therapeutically effective dosing regimen. [0006] In another aspect, the invention features a method of treating a patient suffering from thyroid eye disease (TED), the method comprising administering a pharmaceutical composition comprising an anti-IGF-lR antibody, wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 7, a HCDR2 of SEQ ID NO: 8, and a HCDR3 of SEQ ID NO: 9 and the light chain comprises a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6, wherein the patient, prior to treatment, has had one or more symptoms of thyroid eye disease for at least 12 months. In some embodiments, the anti-IGF-lR antibody is administered at a therapeutically effective dosing regimen. [0007] In some embodiments, a patient, prior to treatment an anti-IGF-lR antibody, has had one or more symptoms of thyroid eye disease for at least 12 months. In some embodiments, a patient, prior to treatment with an anti-IGF-lR antibody, has had one or more symptoms of thyroid eye disease for at least 15 months. In some embodiments, a patient, prior to treatment with an anti-IGF-lR antibody, has had one or more symptoms of thyroid eye disease associated with a Clinical Activity Score (CAS) of > 4, where such symptom(s) have lessened in severity over time. In some embodiments, a patient, prior to treatment with an anti-IGF-lR antibody, has had one or more symptoms of thyroid eye disease that have reached a plateau, e.g., a static some embodiments, a patient, prior to treatment with an anti-IGF-lR antibody, has had one or more symptoms of thyroid eye disease associated with a Clinical Activity Score (CAS) of > 4, where such symptom(s) have lessened in severity over time. In some embodiments, a patient, prior to treatment with an anti-IGF-lR antibody, has had one or more symptoms of thyroid eye disease that have reached a plateau, e.g., a static plateau. . [0008] In some embodiments, a patient suffe