OCULAR IMPLANT CONTAINING A TYROSINE KINASE INHIBITOR

1 . A method of treating an ocular disease in a patient in need thereof, the method comprising administering to the patient a sustained release biodegradable ocular implant comprising a hydrogel and at least about 150 μg of a tyrosine kinase inhibitor (TKI), wherein TKI particles are dispersed within the hydrogel.

2 . The method of claim 1 , wherein the tyrosine kinase inhibitor is axitinib.

3 . The method of claim 2 , wherein the implant comprises axitinib in an amount of about 150 μg to about 1800 μg.

4 . The method of claim 2 , wherein the implant comprises axitinib in an amount of about 150 μg to about 1200 μg.

5 . The method of claim 2 , wherein the implant comprises axitinib in an amount of about 480 μg to about 750 μg.

6 . The method of claim 2 , wherein the implant comprises axitinib in an amount of about 160 pa to about 250 μg.

7 . The method of claim 1 , wherein the implant is administered once during a treatment period of at least 3 months.

8 . The method of claim 7 , wherein the treatment period is about 6 to about 9 months.

9 . The method of claim 7 , wherein the TKI is axitinib and an axitinib dose per eye administered once during the treatment period is from about 150 μg to about 1800 μg, wherein the dose is contained in one implant or in two or more implants administered concurrently.

10 . The method of claim 9 , wherein the axitinib dose per eye administered once during the treatment period is from about 150 μg to 1200 μg.

11 . The method of claim 1 , wherein the ocular disease is a retinal disease.

12 . The method of claim 11 , wherein the retinal disease is selected from the group consisting of neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) or a combination thereof.

13 . The method of claim 12 , wherein the retinal disease is AMD.

14 . The method of claim 13 , wherein the treatment is effective in reducing, essentially maintaining or preventing a clinically significant increase of the central subfield thickness as measured by optical coherence tomography in a patient whose central subfield thickness is elevated.

15 . The method of claim 14 , wherein the patient has been diagnosed with primary subfoveal neovascularization and has or has not been previously treated with an anti-VEGF agent.

16 . The method of claim 1 , wherein the implant is administered by injection into the vitreous humor.

17 . The method of claim 16 , wherein the implant is injected by means of a needle for injection.

18 . The method of claim 17 , wherein the needle for injection is a needle that has a gauge size of 22 to 30.

19 . The method according to claim 1 , wherein concurrently or in combination with the treatment with the sustained release ocular implant an anti-VEGF agent is administered to the patient.

20 . The method of claim 19 , wherein an anti-VEGF agent is administered in combination with the implant, and is administered within about 1, about 2 or about 3 months from the administration of the implant.

21 . The method of claim 19 , wherein the anti-VEGF agent is selected from the group consisting of aflibercept, bevacizumab, pegaptanib, ranibizumab, and brolucizumab and is administered by intravitreous injection.

22 . The method of claim 1 , wherein the implant is administered by injection into the vitreous humor and the TKI is axitinib, wherein a dose administered per eye once during a treatment period of at least 3 months is from about 150 μg to about 1800 μg and is contained in one or more implant(s) administered concurrently.

23 . The method of claim 1 , wherein the implant is administered by injection into the vitreous humor and the TKI is axitinib, wherein a dose administered per eye once during a treatment period of at least 3 months is from about 480 μg to about 750 μg axitinib and is contained in one implant.

24 . The method of claim 1 , wherein the hydrogel comprises polyethylene glycol (PEG) units.

25 . The method of claim 24 , wherein the hydrogel comprises PEG units that have a number average molecular weight of about 20,000 Daltons.

26 . The method of claim 24 , wherein the PEG units comprise 4-arm and/or 8-arm PEG units.

27 . The method of claim 24 , wherein the hydrogel comprises crosslinked PEG units and the crosslinks between the PEG units include a group represented by the following formula

wherein m is an integer from 0 to 10.

28 . The method of claim 27 , wherein m is 6.