Combination therapy for the treatment of neovascular disorders
The invention features methods for treating a patient diagnosed with, or at risk of developing, a neovascular disorder by administering a combination of VEGF antagonists to the patient. The invention also features a pharmaceutical composition containing a first VEGF antagonist and a second VEGF antagonist for the treatment or prevention of a neovascular disorder.
1 . A method for treating a neovascular disease in a patient comprising:
(a) administering a first anti-VEGF agent in an amount effective to inhibit all VEGF isoforms;
(b) administering a second anti-VEGF agent in an amount effective to selectively inhibit VEGF 165 .
2 . A method according to claim 1 wherein said neovascular disorder is an ocular neovascular disorder.
3 . A method according to claim 2 wherein said disorder is macular degeneration.
4 . A method according to claim 2 wherein said first anti-VEGF agent is administered while edema is present.
5 . A method according to claim 4 wherein said second anti-VEGF agent is administered after a response to the first anti-VEGF agent is observed.
6 . A method according to claim 5 wherein said first anti-VEGF agent comprises an antibody or antibody fragment.
7 . A method according to claim 6 wherein said first anti-VEGF agent comprises ranibizumab or bevacizumab.
8 . A method according to claim 7 wherein said second anti-VEGF agent comprises an aptamer.
9 . A method according to claim 8 wherein said aptamer comprises pegaptanib.
10 . A method according to claim 2 wherein said disorder is selected from the group consisting of ischemic retinopathy, iris neovascularization, intraocular neovascularization, age-related macular degeneration, corneal neovascularization, retinal neovascularization, choroidal neovascularization, diabetic retinal ischemia, or proliferative diabetic retinopathy.
11 . A method according to claim 1 wherein said neovascular disorder is selected from the group consisting of cancer, psoriasis or rheumatoid arthritis.
12 . A method for treating a neovascular disorder comprising:
(a) administering a pan-VEGFA inhibitor for a first treatment period; and
(b) administering a selective VEGF inhibitor for a second treatment period.
13 . A method according to claim 12 wherein said selective VEGF inhibitor selectively inhibits VEGF 165 .
14 . A method according to claim 13 wherein said neovascular disorder is selected from the group consisting of ischemic retinopathy, iris neovascularization, intraocular neovascularization, age-related macular degeneration, corneal neovascularization, retinal neovascularization, choroidal neovascularization, diabetic retinal ischemia, proliferative diabetic retinopathy, cancer, rheumatoid arthritis, or psoriasis.
15 . A method according to claim 14 wherein said pan-VEGFA inhibitor is administered every 3-6 weeks.
16 . A method according to claim 15 wherein said selective VEGF inhibitor is administered every 3-12 weeks.
17 . A method according to claim 16 wherein said first treatment period is 3-36 weeks.
18 . A method according to claim 17 wherein said second treatment period is chronic maintenance therapy.
19 . A method according to claim 18 wherein said disorder is macular degeneration.
20 . A method according to claim 19 wherein said pan-VEGFA inhibitor comprises an antibody or antibody fragment.
21 . A method according to claim 20 wherein said pan-VEGFA inhibitor comprises ranibizumab or bevacizumab.
22 . A method according to claim 21 wherein said selective VEGF inhibitor comprises an aptamer.
23 . A method according to claim 22 wherein said selective VEGF inhibitor comprises pegaptanib.
24 . A method according to claim 23 wherein about 0.003-3.0 mg of pegaptanib are administered in each administration.