Compositions, formulations and methods for treating ocular diseases
Disclosed herein are compounds effective for activation of Tie-2 and inhibition of HPTP-beta. The compounds can provide effective therapy for conditions associated with angiogenesis, for example, ocular conditions. Formulations for increased solubility are disclosed. Combination therapy with antibodies and PK/PD data are also disclosed.
1. A method for reducing central retinal thickness in a subject in need thereof, comprising:
administering to the subject a pharmaceutical composition comprising a therapeutically-effective amount of a Tie-2 activator; and
administering to the subject a therapeutically-effective amount of an anti-VEGF agent, wherein the Tie-2 activator is a compound of the formula:
or a pharmaceutically-acceptable salt or zwitterion thereof.
2. The method of claim 1 , wherein the Tie-2 activator inhibits HPTP-β.
3. The method of claim 1 , wherein the subject has diabetic macular edema.
4. The method of claim 1 , wherein the subject has wet age-related macular degeneration.
5. The method of claim 1 , wherein the subject has diabetic retinopathy.
6. The method of claim 1 , wherein the subject has retinal vein occlusion.
7. The method of claim 1 , wherein the administering is by intravitreal injection.
8. The method of claim 1 , wherein the administering is by subconjunctival injection.
9. The method of claim 1 , wherein the administering is by a solid implant.
10. The method of claim 1 , wherein the therapeutically-effective amount of the Tie-2 activator is from about 0.1 mg to about 100 mg.
11. The method of claim 1 , wherein the Tie-2 activator is:
or a pharmaceutically-acceptable salt or zwitterion thereof.
12. The method of claim 1 , wherein the subject is human.
13. The method of claim 1 , wherein the Tie-2 activator and an anti-VEGF agent are administered simultaneously.
14. The method of claim 1 , wherein the Tie-2 activator and an anti-VEGF agent are administered sequentially.
15. The method of claim 1 , wherein the anti-VEGF agent is ranibizumab.
16. The method of claim 1 , wherein the anti-VEGF agent is bevacizumab.
17. The method of claim 1 , wherein the anti-VEGF agent is aflibercept.
18. The method of claim 1 , wherein the anti-VEGF agent is dexamethasone or fluocinolone.