ANTI-C5 AGENT FOR TREATMENT OF DRY AGE-RELATED MACULAR DEGENERATION (AMD) OR GEOGRAPHIC ATROPHY SECONDARY TO DRY AMD
This invention relates to methods and compositions useful for treatment of subjects with dry age-related macular degeneration or geographic atrophy secondary to dry age-related macular degeneration. The methods involve administration of a pharmaceutical composition comprising an anti-05 agent ARC1905, which comprises a C5-specific aptamer conjugated to a polyethylene glycol moeity via a linker, in an amount effective for slowing or inhibiting loss of low luminance visual acuity in the subject. The aptamer consists of the sequence fCmGfCfCGfCmGmGfUfCfUfCmAmGmGfCGfCfUmGmAmGfUfCfUmGmAmGfUfUfUAfCf CfUmGfCmG-3T, wherein fC and fU=2′ fluoro nucleotides, mG and mA=2′-OMe nucleotides, all other nucleotides are 2′-OH, and 3T indicates an inverted deoxythymidine. Dosages and administration schedules are disclosed.
1 . A method for slowing or inhibiting loss of low luminance visual acuity in a subject with geographic atrophy secondary to dry age-related macular degeneration, the method comprising administering to the subject an anti-C5 agent at a dose of about 2 mg/eye,
wherein the anti-C5 agent comprises a C5-specific aptamer comprising the following structure:
or a salt thereof,
wherein Aptamer=fCmGfCfCGfCmGmGfUfCfUfCmAmGmGfCGfCfUmGmAmGfUfC fUmGmAmGfUfUfUAfCfCfUmGfCmG-3T (SEQ ID NO: 1), wherein fC and fU=2′ fluoro nucleotides, mG and mA=2′-OMe nucleotides, all other nucleotides are 2′-OH, and 3T indicates an inverted deoxythymidine.
2 . The method according to claim 1 , wherein the anti-C5 agent is administered intraocularly to the subject via intravitreal injection into the eye.
3 . The method according to claim 1 , wherein the administration of the anti-C5 agent to the subject slows or inhibits the decrease in low luminance best corrected visual acuity as compared to a subject who is not administered the anti-C5 agent.
4 . The method according to claim 1 , wherein the administration of the anti-C5 agent to the subject increases the low luminance best corrected visual acuity as compared to a subject who is not administered the anti-C5 agent.
5 . The method according to claim 3 , wherein the increase is measured between baseline and at least or about 1 month.
6 . The method according to claim 3 , wherein the increase is measured between baseline and at least or about 6 months.
7 . The method according to claim 3 , wherein the increase is measured between baseline and at least or about 8 months.
8 . The method according to claim 3 , wherein the increase is measured between baseline and at least or about 12 months.
9 . The method according to claim 3 , wherein the increase is measured between baseline and at least or about 18 months.
10 . The method according to claim 3 , wherein the increase is measured between baseline and at least or about 24 months.
11 . The method according to claim 1 , wherein the low luminance best corrected visual acuity is measured using ETDRS letters.
12 . The method according to claim 2 , wherein the subject increases the low luminance best corrected visual acuity as compared to a subject who is not administered the anti-C5 agent.
13 . The method according to claim 1 wherein the subject is a subject with GA secondary to dry AMD.
14 . The method according to claim 1 wherein the subject is a subject with GA secondary to AMD.
15 . The method according to claim 1 , wherein subject is human.
16 . The method according to claim 1 , wherein the subject is administered the anti-C5 agent in a loading phase followed by a maintenance phase, wherein the loading phase administering the anti-C5 agent at a dose of about 2 mg/eye for a duration of twelve months at a frequency in which the duration between doses is one month, and wherein the maintenance phase comprises administering the anti-C5 agent at a dose of about 2 mg/eye thereafter at a frequency in which the duration between doses is two months.