1. Emerging treatments on
Neovascular Age Related
Macular Degeneration
Narciso F. Atienza, Jr. MD, DPBO
Cardinal Santos Medical Center
St. Luke’s Medical Center, QC
Legaspi Eye Center
5. Age Related Macular
Degeneration
Progressive eye disease, where photoreceptors loss
function and die
Common in patients 55 years old or above
More common in Caucasians, rare in Negroes
2 broad types
Neovascular (Wet type - Exudative)
Non-neovascular (Dry type - Non exudative)
17. Natural course of AMD (dry)
Majority retain useful vision
10-15% progress to
neovascular AMD
(Risk factors for progression)
Soft drusen
Areas of hyperpigmentation
Presence of CNV on fellow
eye
20. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
21. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
22. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
23. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
24. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
25. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
26. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
27. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
28. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
29. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
30. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
31. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
32. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
Subretinal hemorrhage
33. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
Subretinal hemorrhage
34. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
Subretinal hemorrhage
35. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
Subretinal hemorrhage
Fibrovascular proliferation
36. Neovascular AMD
10% of AMD cases
Main cause of severe visual
loss in AMD
Manifests as
Retinal pigment epithelial
detachment
Choroidal Neovascularization
Subretinal hemorrhage
Fibrovascular proliferation
50. What has been done.........
Macular Photocoagulation Study (MPS)
51. What has been done.........
Macular Photocoagulation Study (MPS)
Photodynamic Therapy (VIP - Verteforfin in Photodynamic
Therapy. TAP - Treatment Of Age-Related Macular
Degeneration With Photodynamic Therapy)
52. What has been done.........
Macular Photocoagulation Study (MPS)
Photodynamic Therapy (VIP - Verteforfin in Photodynamic
Therapy. TAP - Treatment Of Age-Related Macular
Degeneration With Photodynamic Therapy)
Pegaptanib (Macugen)
53. What has been done.........
Macular Photocoagulation Study (MPS)
Photodynamic Therapy (VIP - Verteforfin in Photodynamic
Therapy. TAP - Treatment Of Age-Related Macular
Degeneration With Photodynamic Therapy)
Pegaptanib (Macugen)
V.I.S.I.O.N. - (VEGF Inhibition Study in Ocular
Neovascularization)
56. Ranibizumab (Lucentis)
M.A.R.I.N.A - Minimally classic/occult trial of the Anti-
VEGF antibody Ranibizumab (Lucentis) In the
treatment of Neovascular AMD
57. Ranibizumab (Lucentis)
M.A.R.I.N.A - Minimally classic/occult trial of the Anti-
VEGF antibody Ranibizumab (Lucentis) In the
treatment of Neovascular AMD
ANCHOR (ANti-VEGF Antibody for the Treatment of
Predominantly Classic CHORoidal
Neovascularization in AMD)
79. What’s on the horizon
RADICAL (Reduced fluence visudyne Anti-VEGF-
Dexamethasone In Combination for AMD Lesions).
80. What’s on the horizon
RADICAL (Reduced fluence visudyne Anti-VEGF-
Dexamethasone In Combination for AMD Lesions).
SUMMIT (PDT + Ranibizumab)
81. What’s on the horizon
RADICAL (Reduced fluence visudyne Anti-VEGF-
Dexamethasone In Combination for AMD Lesions).
SUMMIT (PDT + Ranibizumab)
Mont Blanc (European arm) - Standard fluence
82. What’s on the horizon
RADICAL (Reduced fluence visudyne Anti-VEGF-
Dexamethasone In Combination for AMD Lesions).
SUMMIT (PDT + Ranibizumab)
Mont Blanc (European arm) - Standard fluence
DENALI (North American arm) - Reduced fluence
arm
83. What’s on the horizon
RADICAL (Reduced fluence visudyne Anti-VEGF-
Dexamethasone In Combination for AMD Lesions).
SUMMIT (PDT + Ranibizumab)
Mont Blanc (European arm) - Standard fluence
DENALI (North American arm) - Reduced fluence
arm
Everest (Asia arm) - done on polypoidal vasculopathy
91. VEGF Trap
fusion protein specifically designed to bind all forms of
Vascular Endothelial Growth Factor-A (VEGF-A) and
Placental Growth Factor (PLGF).
92. VEGF Trap
fusion protein specifically designed to bind all forms of
Vascular Endothelial Growth Factor-A (VEGF-A) and
Placental Growth Factor (PLGF).
95. VEGF TRAP-EYE
Nguyen QD, Shah SM, Browning DJ, Hudson H, Sonkin P, Hariprasad SM, Kaiser P, Slakter JS, Haller
J, Do DV, Mieler WF, Chu K, Yang K, Ingerman A, Vitti RL, Berliner AJ, Cedarbaum JM, Campochiaro
PA.A phase I study of intravitreal vascular endothelial growth factor
trap-eye in patients with neovascular age-related macular
degeneration.
Ophthalmology. 2009 Nov;116(11):2141-8.e1. Epub 2009 Aug 22.
96. VEGF TRAP-EYE
Doses are as follows: 0.05 mg, 0.15 mg , 0.5 mg, 1
mg, 2 mg, or 4 mg.
Nguyen QD, Shah SM, Browning DJ, Hudson H, Sonkin P, Hariprasad SM, Kaiser P, Slakter JS, Haller
J, Do DV, Mieler WF, Chu K, Yang K, Ingerman A, Vitti RL, Berliner AJ, Cedarbaum JM, Campochiaro
PA.A phase I study of intravitreal vascular endothelial growth factor
trap-eye in patients with neovascular age-related macular
degeneration.
Ophthalmology. 2009 Nov;116(11):2141-8.e1. Epub 2009 Aug 22.
97. VEGF TRAP-EYE
Doses are as follows: 0.05 mg, 0.15 mg , 0.5 mg, 1
mg, 2 mg, or 4 mg.
Decreased foveal thickness average - 104.5 um
Nguyen QD, Shah SM, Browning DJ, Hudson H, Sonkin P, Hariprasad SM, Kaiser P, Slakter JS, Haller
J, Do DV, Mieler WF, Chu K, Yang K, Ingerman A, Vitti RL, Berliner AJ, Cedarbaum JM, Campochiaro
PA.A phase I study of intravitreal vascular endothelial growth factor
trap-eye in patients with neovascular age-related macular
degeneration.
Ophthalmology. 2009 Nov;116(11):2141-8.e1. Epub 2009 Aug 22.
98. VEGF TRAP-EYE
Doses are as follows: 0.05 mg, 0.15 mg , 0.5 mg, 1
mg, 2 mg, or 4 mg.
Decreased foveal thickness average - 104.5 um
Mean increase in VA - 4.43 letters. Higher doses have
13.5 letters improvement (3 lines)
Nguyen QD, Shah SM, Browning DJ, Hudson H, Sonkin P, Hariprasad SM, Kaiser P, Slakter JS, Haller
J, Do DV, Mieler WF, Chu K, Yang K, Ingerman A, Vitti RL, Berliner AJ, Cedarbaum JM, Campochiaro
PA.A phase I study of intravitreal vascular endothelial growth factor
trap-eye in patients with neovascular age-related macular
degeneration.
Ophthalmology. 2009 Nov;116(11):2141-8.e1. Epub 2009 Aug 22.
101. VEGF TRAP-
EYE(Regeneron, Bayer)
A Randomized, Double Masked, Active Controlled
Phase III Study of the Efficacy, Safety, and Tolerability of
Repeated Doses of Intravitreal VEGF Trap in Subjects
With Neovascular Age-Related Macular Degeneration.
102. VEGF TRAP-
EYE(Regeneron, Bayer)
A Randomized, Double Masked, Active Controlled
Phase III Study of the Efficacy, Safety, and Tolerability of
Repeated Doses of Intravitreal VEGF Trap in Subjects
With Neovascular Age-Related Macular Degeneration.
VIEW 1 - US, CANADA
103. VEGF TRAP-
EYE(Regeneron, Bayer)
A Randomized, Double Masked, Active Controlled
Phase III Study of the Efficacy, Safety, and Tolerability of
Repeated Doses of Intravitreal VEGF Trap in Subjects
With Neovascular Age-Related Macular Degeneration.
VIEW 1 - US, CANADA
VIEW 2 - Europe, Asia, South America
116. Epimacular Brachytherapy -
Pilot study
NVI-068
effect of Epimacular
Brachytherapy 24 Gy
Mean gain of 8.9
letters in VA
No loss of vision in
68%
38% gained more
than 15 letters at 12
months
117. Epimacular Brachytherapy -
Pilot study
NVI-068
effect of Epimacular
Brachytherapy 24 Gy
Mean gain of 8.9
letters in VA
No loss of vision in
68%
38% gained more
than 15 letters at 12
months
118. Epimacular Brachytherapy -
Pilot study
NVI-068
effect of Epimacular
Brachytherapy 24 Gy
Mean gain of 8.9
letters in VA
No loss of vision in
68%
38% gained more
than 15 letters at 12
months
119.
120. NVI-111
Strontium 90 + anti-
VEGF agent
(Bevacizumab
1.25mg)
second injection of
Bevacizumab 30
days thereafter.
121. NVI-111
Strontium 90 + anti-
VEGF agent
(Bevacizumab
1.25mg)
second injection of
Bevacizumab 30
days thereafter.
122. NVI-111
Strontium 90 + anti-
VEGF agent
(Bevacizumab
1.25mg)
second injection of
Bevacizumab 30
days thereafter.
123. Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
124. Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
125. Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
126. Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
127. Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
128. Mean change in BCVA
Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
129. Mean change in BCVA
Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
130. Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
131. % of patients losing < 3
more lines in BCVA
Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
132. % of patients losing < 3
more lines in BCVA
Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
133. Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
134. % of patients that gained >
3 lines of VA
Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
135. % of patients that gained >
3 lines of VA
Dugel, P NVI-111 study group
Presented at Retina Congress 2009
Sheraton Towers, New York
143. Off-shoots of the
CABERNET study
MERLOT (Macular EpiRetinal Brachytherapy versus
Lucentis Only Treatment)
Evaluate safety and efficacy of focal delivery of radiation
for the treatment of subfoveal CNV associated with wet
AMD previously treated with anti-VEGF therapy.
144.
145.
146. MERITAGE - still in feasibility.
Evaluate epiretinal beta radiation therapy when used to
treat wet AMD drug persistence in those patients who
have received anti-VEGF therapy.
147. MERITAGE - still in feasibility.
Evaluate epiretinal beta radiation therapy when used to
treat wet AMD drug persistence in those patients who
have received anti-VEGF therapy.
148. MERITAGE - still in feasibility.
Evaluate epiretinal beta radiation therapy when used to
treat wet AMD drug persistence in those patients who
have received anti-VEGF therapy.
ROSE - still in feasibility.
determine the safety and efficacy of epiretinal beta
radiation therapy in those who do not respond to
treatment with anti-VEGF medication.
152. Comparison of Age Related Macular
Degeneration Treatment Trials
Head on comparison between Ranibizumab v.s.
Bevacizumab
153. Comparison of Age Related Macular
Degeneration Treatment Trials
Head on comparison between Ranibizumab v.s.
Bevacizumab
Issues on difference in costs
154. Comparison of Age Related Macular
Degeneration Treatment Trials
Head on comparison between Ranibizumab v.s.
Bevacizumab
Issues on difference in costs
$2000 v.s. $50-100 injection
155. Comparison of Age Related Macular
Degeneration Treatment Trials
Head on comparison between Ranibizumab v.s.
Bevacizumab
Issues on difference in costs
$2000 v.s. $50-100 injection
Resistance from Genentech
157. Regimen
Lucentis on a fixed schedule of every 4 weeks for 1
year; at 1 year, re-randomization to Lucentis every 4
weeks or to variable dosing.
Avastin on a fixed schedule of every 4 weeks for 1
year; at 1 year, re-randomization to Avastin every 4
weeks or to variable dosing.
Lucentis on variable dosing for 2 years; i.e., after initial
treatment, monthly evaluation for treatment based on
signs of lesion activity.
Avastin on variable dosing for 2 years; i.e., after initial
treatment, monthly evaluation for treatment based on
signs of lesion activity.
170. Complement 3 inhibitor
POT-4 - derived from Compstatin
Potentia Pharmaceuticals
ASaP trial (Assessment of Safety of POT-4) - Phase 1
clinical trials.
171. Complement 3 inhibitor
POT-4 - derived from Compstatin
Potentia Pharmaceuticals
ASaP trial (Assessment of Safety of POT-4) - Phase 1
clinical trials.
Well tolerated after a single intra-vitreal dose (1050 ug/
mL)
172. Complement 3 inhibitor
POT-4 - derived from Compstatin
Potentia Pharmaceuticals
ASaP trial (Assessment of Safety of POT-4) - Phase 1
clinical trials.
Well tolerated after a single intra-vitreal dose (1050 ug/
mL)
Now being partnered with Alcon
185. Complement 5 inhibitor
ARC1905 Phase I
Ophthotech Corp.
used with concomitance with Ranibizumab
Preliminary reports showed a 9.5 letters
improvement and decrease in central macular
thickness by 104 um in 1 month.
186. Complement 5 inhibitor
ARC1905 Phase I
Ophthotech Corp.
used with concomitance with Ranibizumab
Preliminary reports showed a 9.5 letters
improvement and decrease in central macular
thickness by 104 um in 1 month.
No retinal toxicity
189. Other targets for AMD
treatment
Platelet derived growth factor inhibition with E10030
(anti-PDGF aptamer)
Phase 1 - with ranibizumab
59% of subjects gained > 15 lines in 12 weeks
+14 letters at 12 weeks from baseline
Mean change in in OCT was 157 um
FA shows decrease in CNV area in 12 weeks by
86%
190.
191. CCR3 - chemokine receptor specifically expressed on
the choroidal endothelium.
192. CCR3 - chemokine receptor specifically expressed on
the choroidal endothelium.
Maybe a more specific target compared to VEGF A
193. CCR3 - chemokine receptor specifically expressed on
the choroidal endothelium.
Maybe a more specific target compared to VEGF A
Can be used as a screening and therapeutic target in
the future.
196. Adenovirus Associated Gene Transfer Vector in murine
equivalent
Maybe used to continually synthesize Bevacizumab in
one single intraocular injection
204. AMD advances
Sustained growth in numbers of patients
Billion dollar industry
Treatment now entails vision improvement and not
just vision preservation
205. AMD advances
Sustained growth in numbers of patients
Billion dollar industry
Treatment now entails vision improvement and not
just vision preservation
Multifaceted approach may work best in treatment.