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Anthony P. Adamis - One of the best experts on this subject based on the ideXlab platform.
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Pegaptanib Sodium for Macular Edema Secondary to Central Retinal Vein Occlusion
Archives of ophthalmology (Chicago Ill. : 1960), 2009Co-Authors: John J. Wroblewski, Anthony P. Adamis, Ronald Buggage, Emmett T. Cunningham, Mauro Goldbaum, Barrett Katz, David R. Guyer, John A. Wells, Michael M. AltaweelAbstract:Objectives To assess the safety and efficacy of intravitreous Pegaptanib sodium for the treatment of macular edema following central retinal vein occlusion (CRVO). Design This dose-ranging, double-masked, multicenter, phase 2 trial included subjects with CRVO for 6 months' or less duration randomly assigned (1:1:1) to receive Pegaptanib sodium or sham injections every 6 weeks for 24 weeks (0.3 mg and 1 mg, n = 33; sham, n = 32). Main Outcome Measure Visual acuity at week 30. Results In the primary analysis at week 30, 12 of 33 (36%) subjects treated with 0.3 mg of Pegaptanib sodium and 13 of 33 (39%) treated with 1 mg gained 15 or more letters from baseline vs 9 of 32 (28%) sham-treated subjects ( P = .48 for 0.3 mg and P = .35 for 1 mg of Pegaptanib sodium vs sham). In secondary analyses, subjects treated with Pegaptanib sodium were less likely to lose 15 or more letters (9% and 6%; 0.3-mg and 1-mg Pegaptanib sodium groups, respectively) compared with sham-treated eyes (31%; P = .03 for 0.3 mg and P = .01 for 1 mg of Pegaptanib sodium vs sham) and showed greater improvement in mean visual acuity (+7.1 and +9.9, respectively, vs −3.2 letters with sham; P = .09 for 0.3 mg and P = .02 for 1 mg of Pegaptanib sodium vs sham). By week 1, the mean central retinal thickness decreased in the 0.3-mg and 1-mg Pegaptanib sodium groups by 269 μm and 210 μm, respectively, vs 5 μm with sham ( P Conclusions Based on this 30-week study, intravitreous Pegaptanib sodium appears to provide visual and anatomical benefits in the treatment of macular edema following CRVO. Application to Clinical Practice Benefits accrued with intravitreous Pegaptanib sodium treatment of macular edema following CRVO suggest a role for vascular endothelial growth factor in the pathogenesis of this condition. Trial Registration clinicaltrials.gov Identifier:NCT00088283
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Pegaptanib sodium for neovascular age-related macular degeneration: third-year safety results of the VEGF Inhibition Study in Ocular Neovascularisation (VISION) trial.
The British journal of ophthalmology, 2008Co-Authors: Lawrence J. Singerman, Harvey Masonson, Manju Patel, Anthony P. Adamis, Ronald Buggage, Emmett T. Cunningham, Mauro Goldbaum, Barrett Katz, David R. GuyerAbstract:Aims: To evaluate the safety of up to 3 years of Pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD). Methods: Two concurrent, prospective, multicentre, double-masked studies randomised subjects with all angiographic lesion compositions of NV-AMD to receive intravitreous Pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to Pegaptanib were rerandomised to continue or discontinue therapy for 48 more weeks; sham-treated subjects continued sham, discontinued or received Pegaptanib. At 102 weeks, subjects receiving Pegaptanib 0.3 mg or 1 mg in years 1 or 2 continued; those receiving Pegaptanib 3 mg or who did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg for year 3. Results: As in years 1 and 2, Pegaptanib was well tolerated in year 3. Adverse events were mainly ocular in nature, mild, transient and injection-related. Serious adverse events were rare. No evidence of systemic safety signals attributed to vascular endothelial growth factor inhibition arose in year 3. There were no findings in relation to vital signs or electrocardiogram results suggesting a relationship to Pegaptanib treatment. Conclusion: The 3-year safety profile of Pegaptanib sodium was favourable in patients with NV-AMD.
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cost effectiveness model for neovascular age related macular degeneration comparing early and late treatment with Pegaptanib sodium based on visual acuity
Value in Health, 2008Co-Authors: Jonathan C Javitt, Stephanie R. Earnshaw, Gergana Zlateva, A Pleil, C N Graham, Anita J Brogan, Sonali N Shah, Anthony P. AdamisAbstract:Objective: To compare the cost-effectiveness of Pegaptanib and usual care within three distinct cohorts of subfoveal neovascular age-related macular degeneration (NV-AMD) patients, that is, those with early, moderate, and late disease, using a comprehensive economic model. Methods: A Markov framework was used to model lifetime movement of a subfoveal NV-AMD cohort through health states based on visual acuity. The model takes a US payer perspective of patients over the age of 65 years. Clinical efficacy was based on published results for the 0.3 mg Pegaptanib and usual care groups. Expert interviews were conducted to determine adverse event treatment patterns and vision rehabilitation resource use. Incidence and costs of comorbidities such as depression and fractures associated with the effects of declining visual acuity were based on our previously published analysis of Medicare data. Transition probabilities were derived from published clinical trial data for each 3-month cycle. Utilities were derived from published sources. Three runs of the model were conducted with cohorts of newly diagnosed patients. Patients were classified as having early, moderate, or late NV-AMD defined as visual acuity in the better-seeing eye of 20/40 to more than 20/80, 20/80 to more than 20/200, and 20/200 to more than 20/400, respectively. Costs and outcomes were discounted 3.0% per annum. Results: Incremental costs per vision-year gained and per quality-adjusted life-year (QALY) gained for early NV-AMD patients were approximately one-third those of patients with late disease ($15,279 vs. $57,230 and $36,282 vs. $132,381, respectively). On average, patients treated early with either Pegaptanib or usual care incurred lower lifetime total direct costs than those treated later. Sensitivity analysis showed that base-case incremental costs per QALY gained for Pegaptanib versus usual care were relatively robust. Conclusions: For patients with subfoveal NV-AMD, treatment with Pegaptanib should be started as early as possible to maximize the clinical and economic benefits.
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Pegaptanib 1-year systemic safety results from a safety-pharmacokinetic trial in patients with neovascular age-related macular degeneration.
Ophthalmology, 2007Co-Authors: Rajendra S. Apte, Harvey Masonson, Manju Patel, Marlene Modi, Lloyd Whitfield, Anthony P. AdamisAbstract:OBJECTIVE To characterize the safety, tolerability, and pharmacokinetics of the pegylated anti-vascular endothelial growth factor (VEGF) aptamer Pegaptanib sodium in subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). DESIGN Prospective 2-cohort study: (1) open-label cohort and (2) randomized, double-masked, uncontrolled multicenter trial. PARTICIPANTS In the combined cohorts, 147 subjects with any angiographic subtype of subfoveal choroidal neovascularization secondary to AMD and best-corrected visual acuities (VAs) in the study eye of 20/40 to 20/320 and in the fellow eye of 20/800 or better received Pegaptanib sodium. INTERVENTION Subjects were randomized to receive intravitreous Pegaptanib sodium (1 mg or 3 mg [3- and 10-fold higher than the 0.3-mg approved dose]) every 6 weeks for 54 weeks. MAIN OUTCOME MEASURES Safety assessments included blood chemistries, urinalyses, vital signs, electrocardiograms, serum antiPegaptanib antibody assays, adverse events, VAs, and intraocular pressures. After the first, fourth, and eighth injections, serial blood samples were obtained for quantification of Pegaptanib plasma concentrations. RESULTS No antiPegaptanib immunoglobulin G (IgG) or IgM antibodies were detected. Few systemic adverse events were noted. Mild or moderate ocular adverse events related to the injection procedure were reported in most patients. Pegaptanib did not accumulate in plasma after multiple doses; systemic exposures were similar after the first, fourth, and eighth doses. The mean apparent terminal half-life was 10 days. Evaluation of blood pressure (BP) and urine protein, both of which are known to be affected by systemic VEGF inhibition, indicated no evidence of a Pegaptanib treatment effect on these parameters. Mean BP at the end of year 1 remained below 140 mmHg (systolic) and 90 mmHg (diastolic), levels considered hypertension by the American College of Cardiology. CONCLUSIONS At doses up to 10-fold higher than the 0.3-mg dose approved for the treatment of AMD, Pegaptanib sodium was well tolerated, with no detectable clinical evidence of systemic VEGF inhibition (i.e., no clinically meaningful changes in proteinuria or mean BP) and no clinically relevant ocular inflammation. Most ocular adverse events were related to the injection procedure itself and were mild or moderate in severity.
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Pegaptanib sodium for the treatment of ocular vascular disease
Expert Review of Ophthalmology, 2007Co-Authors: Emmett T. Cunningham, Anthony P. Adamis, Mauro GoldbaumAbstract:Pegaptanib sodium is a selective RNA aptamer that inhibits the 165 isoform of vascular endothelial growth factor (VEGF), a key regulator of pathological vascular growth and permeability and a contributor to vision loss in diseases such as age-related macular degeneration (AMD), diabetic retinopathy and retinal vein occlusion. The development of Pegaptanib represented an important achievement in that it was both the first approved anti-VEGF agent for the treatment of ocular disease and the first clinically validated aptamer therapeutic. The safety and efficacy of Pegaptanib for the treatment of neovascular AMD were established in the VEGF Inhibition Study in Ocular Neovascularization (VISION) trials. Investigations into the use of Pegaptanib have now been expanded to include diabetic macular edema, macular edema secondary to central retinal vein occlusion and other ocular vascular diseases. Pegaptanib is also being used investigationally in combination with other agents.
Emmett T. Cunningham - One of the best experts on this subject based on the ideXlab platform.
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Pegaptanib Sodium for Macular Edema Secondary to Central Retinal Vein Occlusion
Archives of ophthalmology (Chicago Ill. : 1960), 2009Co-Authors: John J. Wroblewski, Anthony P. Adamis, Ronald Buggage, Emmett T. Cunningham, Mauro Goldbaum, Barrett Katz, David R. Guyer, John A. Wells, Michael M. AltaweelAbstract:Objectives To assess the safety and efficacy of intravitreous Pegaptanib sodium for the treatment of macular edema following central retinal vein occlusion (CRVO). Design This dose-ranging, double-masked, multicenter, phase 2 trial included subjects with CRVO for 6 months' or less duration randomly assigned (1:1:1) to receive Pegaptanib sodium or sham injections every 6 weeks for 24 weeks (0.3 mg and 1 mg, n = 33; sham, n = 32). Main Outcome Measure Visual acuity at week 30. Results In the primary analysis at week 30, 12 of 33 (36%) subjects treated with 0.3 mg of Pegaptanib sodium and 13 of 33 (39%) treated with 1 mg gained 15 or more letters from baseline vs 9 of 32 (28%) sham-treated subjects ( P = .48 for 0.3 mg and P = .35 for 1 mg of Pegaptanib sodium vs sham). In secondary analyses, subjects treated with Pegaptanib sodium were less likely to lose 15 or more letters (9% and 6%; 0.3-mg and 1-mg Pegaptanib sodium groups, respectively) compared with sham-treated eyes (31%; P = .03 for 0.3 mg and P = .01 for 1 mg of Pegaptanib sodium vs sham) and showed greater improvement in mean visual acuity (+7.1 and +9.9, respectively, vs −3.2 letters with sham; P = .09 for 0.3 mg and P = .02 for 1 mg of Pegaptanib sodium vs sham). By week 1, the mean central retinal thickness decreased in the 0.3-mg and 1-mg Pegaptanib sodium groups by 269 μm and 210 μm, respectively, vs 5 μm with sham ( P Conclusions Based on this 30-week study, intravitreous Pegaptanib sodium appears to provide visual and anatomical benefits in the treatment of macular edema following CRVO. Application to Clinical Practice Benefits accrued with intravitreous Pegaptanib sodium treatment of macular edema following CRVO suggest a role for vascular endothelial growth factor in the pathogenesis of this condition. Trial Registration clinicaltrials.gov Identifier:NCT00088283
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Pegaptanib sodium for neovascular age-related macular degeneration: third-year safety results of the VEGF Inhibition Study in Ocular Neovascularisation (VISION) trial.
The British journal of ophthalmology, 2008Co-Authors: Lawrence J. Singerman, Harvey Masonson, Manju Patel, Anthony P. Adamis, Ronald Buggage, Emmett T. Cunningham, Mauro Goldbaum, Barrett Katz, David R. GuyerAbstract:Aims: To evaluate the safety of up to 3 years of Pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD). Methods: Two concurrent, prospective, multicentre, double-masked studies randomised subjects with all angiographic lesion compositions of NV-AMD to receive intravitreous Pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to Pegaptanib were rerandomised to continue or discontinue therapy for 48 more weeks; sham-treated subjects continued sham, discontinued or received Pegaptanib. At 102 weeks, subjects receiving Pegaptanib 0.3 mg or 1 mg in years 1 or 2 continued; those receiving Pegaptanib 3 mg or who did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg for year 3. Results: As in years 1 and 2, Pegaptanib was well tolerated in year 3. Adverse events were mainly ocular in nature, mild, transient and injection-related. Serious adverse events were rare. No evidence of systemic safety signals attributed to vascular endothelial growth factor inhibition arose in year 3. There were no findings in relation to vital signs or electrocardiogram results suggesting a relationship to Pegaptanib treatment. Conclusion: The 3-year safety profile of Pegaptanib sodium was favourable in patients with NV-AMD.
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Pegaptanib sodium for the treatment of ocular vascular disease
Expert Review of Ophthalmology, 2007Co-Authors: Emmett T. Cunningham, Anthony P. Adamis, Mauro GoldbaumAbstract:Pegaptanib sodium is a selective RNA aptamer that inhibits the 165 isoform of vascular endothelial growth factor (VEGF), a key regulator of pathological vascular growth and permeability and a contributor to vision loss in diseases such as age-related macular degeneration (AMD), diabetic retinopathy and retinal vein occlusion. The development of Pegaptanib represented an important achievement in that it was both the first approved anti-VEGF agent for the treatment of ocular disease and the first clinically validated aptamer therapeutic. The safety and efficacy of Pegaptanib for the treatment of neovascular AMD were established in the VEGF Inhibition Study in Ocular Neovascularization (VISION) trials. Investigations into the use of Pegaptanib have now been expanded to include diabetic macular edema, macular edema secondary to central retinal vein occlusion and other ocular vascular diseases. Pegaptanib is also being used investigationally in combination with other agents.
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Pegaptanib sodium for ocular vascular disease.
Indian journal of ophthalmology, 2007Co-Authors: Dhananjay Shukla, P Namperumalsamy, Mauro Goldbaum, Emmett T. CunninghamAbstract:Pegaptanib sodium (Macugen) is a selective RNA aptamer that inhibits vascular endothelial growth factor (VEGF) 165 , the VEGF isoform primarily responsible for pathologic ocular neovascularization and vascular permeability, while sparing the physiological isoform VEGF 121 . After more than 10 years in development and preclinical study, Pegaptanib was shown in clinical trials to be effective in treating choroidal neovascularization associated with age-related macular degeneration. Its excellent ocular and systemic safety profile has also been confirmed in patients receiving up to three years of therapy. Early, well-controlled studies further suggest that Pegaptanib may provide therapeutic benefit for patients with diabetic macular edema, proliferative diabetic retinopathy and retinal vein occlusion. Notably, Pegaptanib was the first available aptamer approved for therapeutic use in humans and the first VEGF inhibitor available for the treatment of ocular vascular diseases.
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Year 2 efficacy results of 2 randomized controlled clinical trials of Pegaptanib for neovascular age-related macular degeneration.
Ophthalmology, 2006Co-Authors: U Chakravarthy, Ap Adamis, Emmett T. Cunningham, Mauro Goldbaum, Barrett Katz, David R. Guyer, Manju PatelAbstract:To evaluate the efficacy of a second year of Pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization] trials). Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102. At week 54, those initially assigned to Pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 Pegaptanib doses. Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of > or =15 letters from week 54 to week 102; losing <15 letters (responders) from baseline to week 102; gaining > or =0, > or =1, > or =2, and > or =3 lines of VA; and progressing to legal blindness (20/200 or worse). In combined analysis, mean VA was maintained in patients continuing with 0.3-mg Pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued Pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued Pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg Pegaptanib for a second year were less likely to lose > or =15 letters than those re-randomized to discontinue after 1 year (P<0.05). The proportion of patients gaining vision was higher for those assigned to 2 years of 0.3-mg Pegaptanib than receiving usual care. Progression to legal blindness was reduced for patients continuing 0.3-mg Pegaptanib for 2 years. Continuing visual benefit was observed in patients who were randomized to receive therapy with Pegaptanib in year 2 of the V.I.S.I.O.N. trials when compared with 2 years' usual care or cessation of therapy at year 1.
Rajendra S. Apte - One of the best experts on this subject based on the ideXlab platform.
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Pegaptanib sodium for the treatment of age-related macular degeneration
Expert opinion on pharmacotherapy, 2008Co-Authors: Rajendra S. ApteAbstract:Background: Pegaptanib sodium, the first aptamer therapeutic approved for use and the first antiangiogenic agent used to treat ocular neovascular disease, acts by inhibiting the 165 isoform of vascular endothelial growth factor believed primarily responsible for pathologic ocular neovascularization and vascular permeability. Objective: To briefly present the pharmacology, clinical efficacy and safety, and role of Pegaptanib in treating ocular neovascular diseases. Methods: A systematic literature review and synopsis. Results/conclusion: After more than 10 years in development, clinical trials have shown Pegaptanib efficacy in treating choroidal neovascularization of age-related macular degeneration. Its excellent ocular and systemic safety profiles have been confirmed in up to 3 years of experience. Early phase, well-controlled studies also suggest therapeutic benefit in diabetic retinopathy and retinal vein occlusion.
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Pegaptanib 1-year systemic safety results from a safety-pharmacokinetic trial in patients with neovascular age-related macular degeneration.
Ophthalmology, 2007Co-Authors: Rajendra S. Apte, Harvey Masonson, Manju Patel, Marlene Modi, Lloyd Whitfield, Anthony P. AdamisAbstract:OBJECTIVE To characterize the safety, tolerability, and pharmacokinetics of the pegylated anti-vascular endothelial growth factor (VEGF) aptamer Pegaptanib sodium in subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). DESIGN Prospective 2-cohort study: (1) open-label cohort and (2) randomized, double-masked, uncontrolled multicenter trial. PARTICIPANTS In the combined cohorts, 147 subjects with any angiographic subtype of subfoveal choroidal neovascularization secondary to AMD and best-corrected visual acuities (VAs) in the study eye of 20/40 to 20/320 and in the fellow eye of 20/800 or better received Pegaptanib sodium. INTERVENTION Subjects were randomized to receive intravitreous Pegaptanib sodium (1 mg or 3 mg [3- and 10-fold higher than the 0.3-mg approved dose]) every 6 weeks for 54 weeks. MAIN OUTCOME MEASURES Safety assessments included blood chemistries, urinalyses, vital signs, electrocardiograms, serum antiPegaptanib antibody assays, adverse events, VAs, and intraocular pressures. After the first, fourth, and eighth injections, serial blood samples were obtained for quantification of Pegaptanib plasma concentrations. RESULTS No antiPegaptanib immunoglobulin G (IgG) or IgM antibodies were detected. Few systemic adverse events were noted. Mild or moderate ocular adverse events related to the injection procedure were reported in most patients. Pegaptanib did not accumulate in plasma after multiple doses; systemic exposures were similar after the first, fourth, and eighth doses. The mean apparent terminal half-life was 10 days. Evaluation of blood pressure (BP) and urine protein, both of which are known to be affected by systemic VEGF inhibition, indicated no evidence of a Pegaptanib treatment effect on these parameters. Mean BP at the end of year 1 remained below 140 mmHg (systolic) and 90 mmHg (diastolic), levels considered hypertension by the American College of Cardiology. CONCLUSIONS At doses up to 10-fold higher than the 0.3-mg dose approved for the treatment of AMD, Pegaptanib sodium was well tolerated, with no detectable clinical evidence of systemic VEGF inhibition (i.e., no clinically meaningful changes in proteinuria or mean BP) and no clinically relevant ocular inflammation. Most ocular adverse events were related to the injection procedure itself and were mild or moderate in severity.
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Retinal pigment epithelial tear following intravitreal Pegaptanib sodium.
American journal of ophthalmology, 2006Co-Authors: Mandeep Singh Dhalla, Seenu M Hariprasad, Kevin J. Blinder, A. Tewari, Rajendra S. ApteAbstract:Purpose To report two cases of a retinal pigment epithelial tear after intravitreal injection of Pegaptanib sodium. To our knowledge, this is the first report of this finding after intraocular antivascular endothelial growth factor therapy. Design Observational case reports. Methods Two patients presented with occult choroidal neovascularization and associated serous pigment epithelial detachment that was a result of age-related macular degeneration. Both patients were treated with an intravitreal injection of Pegaptanib sodium. Results One patient developed a retinal pigment epithelium tear one week after the intravitreal injection. The second patient developed a retinal pigment epithelium tear eight weeks after treatment. Conclusions Although these cases may represent natural history, there should be a high index of suspicion for retinal pigment epithelium tears in patients who report significant visual deterioration after intravitreal injection of Pegaptanib sodium. Further studies are needed to determine whether angiographic subtypes of choroidal neovascular membranes are more susceptible to developing retinal pigment epithelium tears after treatment with antivascular endothelial growth factor agents.
David R. Guyer - One of the best experts on this subject based on the ideXlab platform.
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Pegaptanib Sodium for Macular Edema Secondary to Central Retinal Vein Occlusion
Archives of ophthalmology (Chicago Ill. : 1960), 2009Co-Authors: John J. Wroblewski, Anthony P. Adamis, Ronald Buggage, Emmett T. Cunningham, Mauro Goldbaum, Barrett Katz, David R. Guyer, John A. Wells, Michael M. AltaweelAbstract:Objectives To assess the safety and efficacy of intravitreous Pegaptanib sodium for the treatment of macular edema following central retinal vein occlusion (CRVO). Design This dose-ranging, double-masked, multicenter, phase 2 trial included subjects with CRVO for 6 months' or less duration randomly assigned (1:1:1) to receive Pegaptanib sodium or sham injections every 6 weeks for 24 weeks (0.3 mg and 1 mg, n = 33; sham, n = 32). Main Outcome Measure Visual acuity at week 30. Results In the primary analysis at week 30, 12 of 33 (36%) subjects treated with 0.3 mg of Pegaptanib sodium and 13 of 33 (39%) treated with 1 mg gained 15 or more letters from baseline vs 9 of 32 (28%) sham-treated subjects ( P = .48 for 0.3 mg and P = .35 for 1 mg of Pegaptanib sodium vs sham). In secondary analyses, subjects treated with Pegaptanib sodium were less likely to lose 15 or more letters (9% and 6%; 0.3-mg and 1-mg Pegaptanib sodium groups, respectively) compared with sham-treated eyes (31%; P = .03 for 0.3 mg and P = .01 for 1 mg of Pegaptanib sodium vs sham) and showed greater improvement in mean visual acuity (+7.1 and +9.9, respectively, vs −3.2 letters with sham; P = .09 for 0.3 mg and P = .02 for 1 mg of Pegaptanib sodium vs sham). By week 1, the mean central retinal thickness decreased in the 0.3-mg and 1-mg Pegaptanib sodium groups by 269 μm and 210 μm, respectively, vs 5 μm with sham ( P Conclusions Based on this 30-week study, intravitreous Pegaptanib sodium appears to provide visual and anatomical benefits in the treatment of macular edema following CRVO. Application to Clinical Practice Benefits accrued with intravitreous Pegaptanib sodium treatment of macular edema following CRVO suggest a role for vascular endothelial growth factor in the pathogenesis of this condition. Trial Registration clinicaltrials.gov Identifier:NCT00088283
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Pegaptanib sodium for neovascular age-related macular degeneration: third-year safety results of the VEGF Inhibition Study in Ocular Neovascularisation (VISION) trial.
The British journal of ophthalmology, 2008Co-Authors: Lawrence J. Singerman, Harvey Masonson, Manju Patel, Anthony P. Adamis, Ronald Buggage, Emmett T. Cunningham, Mauro Goldbaum, Barrett Katz, David R. GuyerAbstract:Aims: To evaluate the safety of up to 3 years of Pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD). Methods: Two concurrent, prospective, multicentre, double-masked studies randomised subjects with all angiographic lesion compositions of NV-AMD to receive intravitreous Pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to Pegaptanib were rerandomised to continue or discontinue therapy for 48 more weeks; sham-treated subjects continued sham, discontinued or received Pegaptanib. At 102 weeks, subjects receiving Pegaptanib 0.3 mg or 1 mg in years 1 or 2 continued; those receiving Pegaptanib 3 mg or who did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg for year 3. Results: As in years 1 and 2, Pegaptanib was well tolerated in year 3. Adverse events were mainly ocular in nature, mild, transient and injection-related. Serious adverse events were rare. No evidence of systemic safety signals attributed to vascular endothelial growth factor inhibition arose in year 3. There were no findings in relation to vital signs or electrocardiogram results suggesting a relationship to Pegaptanib treatment. Conclusion: The 3-year safety profile of Pegaptanib sodium was favourable in patients with NV-AMD.
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Year 2 efficacy results of 2 randomized controlled clinical trials of Pegaptanib for neovascular age-related macular degeneration.
Ophthalmology, 2006Co-Authors: U Chakravarthy, Ap Adamis, Emmett T. Cunningham, Mauro Goldbaum, Barrett Katz, David R. Guyer, Manju PatelAbstract:To evaluate the efficacy of a second year of Pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization] trials). Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102. At week 54, those initially assigned to Pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 Pegaptanib doses. Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of > or =15 letters from week 54 to week 102; losing <15 letters (responders) from baseline to week 102; gaining > or =0, > or =1, > or =2, and > or =3 lines of VA; and progressing to legal blindness (20/200 or worse). In combined analysis, mean VA was maintained in patients continuing with 0.3-mg Pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued Pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued Pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg Pegaptanib for a second year were less likely to lose > or =15 letters than those re-randomized to discontinue after 1 year (P<0.05). The proportion of patients gaining vision was higher for those assigned to 2 years of 0.3-mg Pegaptanib than receiving usual care. Progression to legal blindness was reduced for patients continuing 0.3-mg Pegaptanib for 2 years. Continuing visual benefit was observed in patients who were randomized to receive therapy with Pegaptanib in year 2 of the V.I.S.I.O.N. trials when compared with 2 years' usual care or cessation of therapy at year 1.
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year 2 efficacy results of 2 randomized controlled clinical trials of Pegaptanib for neovascular age related macular degeneration
Ophthalmology, 2006Co-Authors: U Chakravarthy, Anthony P. Adamis, Emmett T. Cunningham, Mauro Goldbaum, David R. Guyer, Bradley J Katz, Manju PatelAbstract:OBJECTIVE: To evaluate the efficacy of a second year of Pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). DESIGN: Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization] trials). PARTICIPANTS: Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102. INTERVENTIONS: At week 54, those initially assigned to Pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 Pegaptanib doses. MAIN OUTCOME MEASURES: Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of > or =15 letters from week 54 to week 102; losing or =0, > or =1, > or =2, and > or =3 lines of VA; and progressing to legal blindness (20/200 or worse). RESULTS: In combined analysis, mean VA was maintained in patients continuing with 0.3-mg Pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued Pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued Pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg Pegaptanib for a second year were less likely to lose > or =15 letters than those re-randomized to discontinue after 1 year (P<0.05). The proportion of patients gaining vision was higher for those assigned to 2 years of 0.3-mg Pegaptanib than receiving usual care. Progression to legal blindness was reduced for patients continuing 0.3-mg Pegaptanib for 2 years. CONCLUSIONS: Continuing visual benefit was observed in patients who were randomized to receive therapy with Pegaptanib in year 2 of the V.I.S.I.O.N. trials when compared with 2 years' usual care or cessation of therapy at year 1.
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Year 2 efficacy results of 2 randomized controlled clinical trials of Pegaptanib for neovascular age-related macular degeneration.
Ophthalmology, 2006Co-Authors: U Chakravarthy, Anthony P. Adamis, Emmett T. Cunningham, Mauro Goldbaum, David R. Guyer, Bradley J Katz, Manju PatelAbstract:OBJECTIVE: To evaluate the efficacy of a second year of Pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). DESIGN: Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization] trials). PARTICIPANTS: Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102. INTERVENTIONS: At week 54, those initially assigned to Pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 Pegaptanib doses. MAIN OUTCOME MEASURES: Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of > or =15 letters from week 54 to week 102; losing or =0, > or =1, > or =2, and > or =3 lines of VA; and progressing to legal blindness (20/200 or worse). RESULTS: In combined analysis, mean VA was maintained in patients continuing with 0.3-mg Pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued Pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued Pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg Pegaptanib for a second year were less likely to lose > or =15 letters than those re-randomized to discontinue after 1 year (P
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Pegaptanib sodium for neovascular age-related macular degeneration: third-year safety results of the VEGF Inhibition Study in Ocular Neovascularisation (VISION) trial.
The British journal of ophthalmology, 2008Co-Authors: Lawrence J. Singerman, Harvey Masonson, Manju Patel, Anthony P. Adamis, Ronald Buggage, Emmett T. Cunningham, Mauro Goldbaum, Barrett Katz, David R. GuyerAbstract:Aims: To evaluate the safety of up to 3 years of Pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD). Methods: Two concurrent, prospective, multicentre, double-masked studies randomised subjects with all angiographic lesion compositions of NV-AMD to receive intravitreous Pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to Pegaptanib were rerandomised to continue or discontinue therapy for 48 more weeks; sham-treated subjects continued sham, discontinued or received Pegaptanib. At 102 weeks, subjects receiving Pegaptanib 0.3 mg or 1 mg in years 1 or 2 continued; those receiving Pegaptanib 3 mg or who did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg for year 3. Results: As in years 1 and 2, Pegaptanib was well tolerated in year 3. Adverse events were mainly ocular in nature, mild, transient and injection-related. Serious adverse events were rare. No evidence of systemic safety signals attributed to vascular endothelial growth factor inhibition arose in year 3. There were no findings in relation to vital signs or electrocardiogram results suggesting a relationship to Pegaptanib treatment. Conclusion: The 3-year safety profile of Pegaptanib sodium was favourable in patients with NV-AMD.
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Pegaptanib 1-year systemic safety results from a safety-pharmacokinetic trial in patients with neovascular age-related macular degeneration.
Ophthalmology, 2007Co-Authors: Rajendra S. Apte, Harvey Masonson, Manju Patel, Marlene Modi, Lloyd Whitfield, Anthony P. AdamisAbstract:OBJECTIVE To characterize the safety, tolerability, and pharmacokinetics of the pegylated anti-vascular endothelial growth factor (VEGF) aptamer Pegaptanib sodium in subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). DESIGN Prospective 2-cohort study: (1) open-label cohort and (2) randomized, double-masked, uncontrolled multicenter trial. PARTICIPANTS In the combined cohorts, 147 subjects with any angiographic subtype of subfoveal choroidal neovascularization secondary to AMD and best-corrected visual acuities (VAs) in the study eye of 20/40 to 20/320 and in the fellow eye of 20/800 or better received Pegaptanib sodium. INTERVENTION Subjects were randomized to receive intravitreous Pegaptanib sodium (1 mg or 3 mg [3- and 10-fold higher than the 0.3-mg approved dose]) every 6 weeks for 54 weeks. MAIN OUTCOME MEASURES Safety assessments included blood chemistries, urinalyses, vital signs, electrocardiograms, serum antiPegaptanib antibody assays, adverse events, VAs, and intraocular pressures. After the first, fourth, and eighth injections, serial blood samples were obtained for quantification of Pegaptanib plasma concentrations. RESULTS No antiPegaptanib immunoglobulin G (IgG) or IgM antibodies were detected. Few systemic adverse events were noted. Mild or moderate ocular adverse events related to the injection procedure were reported in most patients. Pegaptanib did not accumulate in plasma after multiple doses; systemic exposures were similar after the first, fourth, and eighth doses. The mean apparent terminal half-life was 10 days. Evaluation of blood pressure (BP) and urine protein, both of which are known to be affected by systemic VEGF inhibition, indicated no evidence of a Pegaptanib treatment effect on these parameters. Mean BP at the end of year 1 remained below 140 mmHg (systolic) and 90 mmHg (diastolic), levels considered hypertension by the American College of Cardiology. CONCLUSIONS At doses up to 10-fold higher than the 0.3-mg dose approved for the treatment of AMD, Pegaptanib sodium was well tolerated, with no detectable clinical evidence of systemic VEGF inhibition (i.e., no clinically meaningful changes in proteinuria or mean BP) and no clinically relevant ocular inflammation. Most ocular adverse events were related to the injection procedure itself and were mild or moderate in severity.
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Local tolerance and systemic safety of Pegaptanib sodium in the dog and rabbit.
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2007Co-Authors: Jeffrey W.-d. Foy, Kay D. Rittenhouse, Marlene Modi, Manju PatelAbstract:Purpose: To evaluate the local tolerance, systemic toxicity, and toxicokinetics in dogs and rabbits of Pegaptanib sodium, an aptamer that targets vascular endothelial growth factor (VEGF165). Methods: Dogs received biweekly, bilateral, intravitreous (IVT) injections of Pegaptanib sodium for 9 months at doses of 0.3 (n = 10), 1 (n = 10), or 3 mg (n = 14); 14 control dogs received phosphate-buffered saline (PBS). In rabbits, Pegaptanib sodium was administered by IVT injection biweekly for 6 months at doses of 0.2 (n = 14), 0.67 (n = 14), or 2 mg (n = 18); 18 rabbits received PBS. The systemic and ocular safety of Pegaptanib sodium was assessed. Assessments in both dogs and rabbits included complete ophthalmologic examinations, serum chemistry, hematology, urinalysis, and coagulation assessments, as well as gross and microscopic pathologic examination. In addition, dogs were assessed by electroretinography and electrocardiography. In a cardiovascular safety study, loading intravenous boluses and maintenance ...
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Year 2 efficacy results of 2 randomized controlled clinical trials of Pegaptanib for neovascular age-related macular degeneration.
Ophthalmology, 2006Co-Authors: U Chakravarthy, Ap Adamis, Emmett T. Cunningham, Mauro Goldbaum, Barrett Katz, David R. Guyer, Manju PatelAbstract:To evaluate the efficacy of a second year of Pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization] trials). Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102. At week 54, those initially assigned to Pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 Pegaptanib doses. Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of > or =15 letters from week 54 to week 102; losing <15 letters (responders) from baseline to week 102; gaining > or =0, > or =1, > or =2, and > or =3 lines of VA; and progressing to legal blindness (20/200 or worse). In combined analysis, mean VA was maintained in patients continuing with 0.3-mg Pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued Pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued Pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg Pegaptanib for a second year were less likely to lose > or =15 letters than those re-randomized to discontinue after 1 year (P<0.05). The proportion of patients gaining vision was higher for those assigned to 2 years of 0.3-mg Pegaptanib than receiving usual care. Progression to legal blindness was reduced for patients continuing 0.3-mg Pegaptanib for 2 years. Continuing visual benefit was observed in patients who were randomized to receive therapy with Pegaptanib in year 2 of the V.I.S.I.O.N. trials when compared with 2 years' usual care or cessation of therapy at year 1.
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year 2 efficacy results of 2 randomized controlled clinical trials of Pegaptanib for neovascular age related macular degeneration
Ophthalmology, 2006Co-Authors: U Chakravarthy, Anthony P. Adamis, Emmett T. Cunningham, Mauro Goldbaum, David R. Guyer, Bradley J Katz, Manju PatelAbstract:OBJECTIVE: To evaluate the efficacy of a second year of Pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). DESIGN: Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization] trials). PARTICIPANTS: Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102. INTERVENTIONS: At week 54, those initially assigned to Pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 Pegaptanib doses. MAIN OUTCOME MEASURES: Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of > or =15 letters from week 54 to week 102; losing or =0, > or =1, > or =2, and > or =3 lines of VA; and progressing to legal blindness (20/200 or worse). RESULTS: In combined analysis, mean VA was maintained in patients continuing with 0.3-mg Pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued Pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued Pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg Pegaptanib for a second year were less likely to lose > or =15 letters than those re-randomized to discontinue after 1 year (P<0.05). The proportion of patients gaining vision was higher for those assigned to 2 years of 0.3-mg Pegaptanib than receiving usual care. Progression to legal blindness was reduced for patients continuing 0.3-mg Pegaptanib for 2 years. CONCLUSIONS: Continuing visual benefit was observed in patients who were randomized to receive therapy with Pegaptanib in year 2 of the V.I.S.I.O.N. trials when compared with 2 years' usual care or cessation of therapy at year 1.