Avner Ingerman

Regeneron, Terryville, New York, United States

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Publications (5)21.06 Total impact

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    ABSTRACT: Abstract Purpose: To determine bioactivity and duration of effect of intravitreal aflibercept injection (also known as vascular endothelial growth factor Trap-Eye) for neovascular age-related macular degeneration (AMD). Methods: In this double-masked, phase 1 study, 28 patients with lesions ≤12 disc areas, ≥50% active choroidal neovascularization (CNV), and best corrected visual acuity (BCVA) ≤20/40 were randomized 1:1 to a single intravitreal injection of aflibercept 0.15 or 4 mg. The primary end point was the change from baseline in central retinal/lesion thickness (CR/LT) at week-8. Secondary outcomes were the change from baseline BCVA, the change in CNV lesion size and area of leakage, and proportion of patients requiring repeat injection at 8 weeks. Results: Mean percent decrease in CR/LT for the 4-mg and 0.15-mg groups was, respectively, 34.2 versus 13.3 at week 4 (P=0.0065), 23.8 versus 5.9 at week 6 (P=0.0380), and 25.2% versus 11.3% at week 8 (P=0.150). The 4-mg group gained a mean of 4.5 letters in BCVA (6/14 patients gaining ≥10 letters) versus 1.1 letters in 0.15-mg group (1/14 gaining ≥10 letters) at week 8. Fewer patients needed retreatment in the 4-mg group at week 8. No serious adverse event or ocular inflammation was reported in either group. Conclusions: Intravitreal aflibercept 4 mg had a safety profile similar to that of the very low dose 0.15 mg, and was well-tolerated. The 4-mg dose significantly reduced foveal thickening at weeks 4 and 6, significantly improved BCVA at weeks 6, and reduced the need for repeat injection after 8 weeks compared with intravitreal aflibercept 0.15 mg in neovascular AMD patients.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 07/2012; · 1.46 Impact Factor
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    ABSTRACT: To evaluate anatomic outcomes and vision, injection frequency, and safety during the as-needed (PRN) treatment phase of a study evaluating a 12-week fixed dosing period followed by PRN dosing to week 52 with vascular endothelial growth factor (VEGF) Trap-Eye for neovascular (wet) age-related macular degeneration (AMD). Multicenter, randomized, double-masked trial. We included 159 patients with subfoveal choroidal neovascularization (CNV) secondary to wet AMD. Patients were randomly assigned to 1 of 5 intravitreal VEGF Trap-Eye treatment groups: 0.5 mg or 2 mg every 4 weeks or 0.5, 2, or 4 mg every 12 weeks during the fixed-dosing period (weeks 1-12). From weeks 16 to 52, patients were evaluated monthly and were retreated PRN with their assigned dose (0.5, 2, or 4 mg). Change in central retinal/lesion thickness (CR/LT), change in total lesion and CNV size, mean change in best-corrected visual acuity (BCVA), proportion of patients with 15-letter loss or gain, time to first PRN injection, reinjection frequency, and safety at week 52. The decrease in CR/LT at week 12 versus baseline remained significant at weeks 12 to 52 (-130 μm from baseline at week 52) and CNV size regressed from baseline by 2.21 mm(2) at 48 weeks. After achieving a significant improvement in BCVA during the 12-week, fixed-dosing phase for all groups combined, PRN dosing for 40 weeks maintained improvements in BCVA to 52 weeks (5.3-letter gain; P<0.0001). The most robust improvements and consistent maintenance of visual acuity generally occurred in patients initially dosed with 2 mg every 4 weeks for 12 weeks, demonstrating a gain of 9 letters at 52 weeks. Overall, a mean of 2 injections was administered after the 12-week fixed-dosing phase, and the mean time to first reinjection was 129 days; 19% of patients received no injections and 45% received 1 or 2 injections. Treatment with VEGF Trap-Eye was generally safe and well tolerated, with few ocular or systemic adverse events. PRN dosing with VEGF Trap-Eye at weeks 16-52 maintained the significant anatomic and vision improvements established during the 12-week fixed-dosing phase with a low frequency of reinjections. Repeated dosing with VEGF Trap-Eye was well tolerated over 52 weeks of treatment. Proprietary or commercial disclosure may be found after the references.
    Ophthalmology 06/2011; 118(6):1098-106. · 5.56 Impact Factor
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    ABSTRACT: To evaluate the biologic effects and safety of vascular endothelial growth factor (VEGF) Trap-Eye during a 12-week fixed-dosing period in patients with neovascular (wet) age-related macular degeneration (AMD). Multicenter, prospective, randomized, double-masked clinical trial with initial 12-week fixed dosing period. Data were analyzed to week 16. We included 159 patients with subfoveal choroidal neovascularization secondary to wet AMD. Patients were randomized 1:1:1:1:1 to VEGF Trap-Eye during the fixed-dosing phase (day 1 to week 12): 0.5 or 2 mg every 4 weeks (0.5 mg q4wk, 2 mg q4wk) on day 1 and at weeks 4, 8, and 12; or 0.5, 2, or 4 mg every 12 weeks (0.5 mg q12wk, 2 mg q12wk, or 4 mg q12wk) on day 1 and at week 12. The primary endpoint was change from baseline in central retinal/lesion thickness (CR/LT) at week 12; secondary outcomes included change in best-corrected visual acuity (BCVA), proportion of patients with a gain of ≥ 15 letters, proportion of patients with a loss of >15 letters, and safety. At week 12, treatment with VEGF Trap-Eye resulted in a significant mean decrease in CR/LT of 119 μm from baseline in all groups combined (P<0.0001). The reduction in CR/LT with the 2 mg q4wk and 0.5mg q4wk regimens was significantly greater than each of the quarterly dosing regimens. The BCVA increased significantly by a mean of 5.7 letters at 12 weeks in the combined group (P<0.0001), with the greatest mean gain of >8 letters in the monthly dosing groups. At 8 weeks, BCVA improvements were similar with 2 mg q4wk and 2 mg q12wk dosing. After the last required dose at week 12, CR/LT and visual acuity were maintained or further improved at week 16 in all treatment groups. Ocular adverse events were mild and consistent with safety profiles reported for other intraocular anti-VEGF treatments. Repeated monthly intravitreal dosing of VEGF Trap-Eye over 12 weeks demonstrated significant reductions in retinal thickness and improvements in visual acuity, and was well-tolerated in patients with neovascular AMD. Proprietary or commercial disclosure may be found after the references.
    Ophthalmology 06/2011; 118(6):1089-97. · 5.56 Impact Factor
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    ABSTRACT: To determine the safety, tolerability, maximum tolerated dose, and bioactivity of an intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye, a fusion protein of binding domains from human VEGF receptors 1 and 2 with human immunoglobulin-G Fc that binds VEGF family members, in patients with neovascular age-related macular degeneration (AMD). Dose-escalation, multicenter, interventional clinical trial. Twenty-one patients (13 female, 8 male) with neovascular AMD (NVAMD) and lesions <or=12 disc areas in size and >or=50% active choroidal neovascularization (CNV) with best-corrected visual acuity (BCVA) <or=20/40 received a single intraocular injection of 0.05 mg (n = 3), 0.15 mg (n = 3), 0.5 mg (n = 3), 1 mg (n = 6), 2 mg (n = 3), or 4 mg (n = 3) of VEGF Trap-Eye. Safety assessments included eye examinations, vital signs, and laboratory tests. Measures of bioactivity included changes from baseline in BCVA, optical coherence tomography (OCT), and fluorescein angiography. The primary end point was 6 weeks and patients were followed up for 12 weeks. Safety assessments. There were no serious adverse events and no identifiable intraocular inflammation. The mean decrease in excess foveal thickness for all patients was 104.5 mum at 6 weeks, and the mean increase in visual acuity was 4.43 letters. In the 2 highest dose groups combined (2 and 4 mg), the mean increase in BCVA was 13.5 letters, with 3 of 6 patients demonstrating improvement of >or=3 lines and 3 patients requiring no adjunctive treatment of any type for 12 weeks. Some showed elimination of fluorescein leakage and reduction in area of CNV. Intravitreal injection of up to 4 mg of VEGF Trap-Eye in patients with NVAMD was well tolerated with no evidence of ocular inflammation. Although the number of patients in each cohort was small, there was evidence of bioactivity, because several patients, especially those receiving 2 or 4 mg of VEGF Trap-Eye, showed substantial improvement in BCVA associated with reductions in foveal thickness. Phase III trials to investigate the efficacy of intraocular VEGF Trap-Eye in patients with NVAMD are under way.
    Ophthalmology 08/2009; 116(11):2141-8.e1. · 5.56 Impact Factor
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    ABSTRACT: The aim of the study was to assess the safety and bioactivity of a single intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye in subjects with diabetic macular oedema (DMO). Five subjects with DMO, foveal thickness > or =250 microm measured by optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) between 20/40 and 20/320, were enrolled. Each participant received a single intravitreal injection of 4.0 mg of VEGF Trap-Eye followed by a 6-week observation period. Outcome measures included safety and biological activity, including changes in BCVA and excess retinal thickness assessed by OCT. Injections of VEGF Trap-Eye were well tolerated with no ocular toxicity. One patient had an unrelated serious adverse event: hospitalisation for cellulitis of the left foot 27 days after injection of VEGF Trap-Eye. Median baseline BCVA was 36 ETDRS letters read at 4 m (not ETDRS visual acuity score; Snellen equivalent: 20/50) and median baseline excess central 1 mm foveal thickness (FTH) was 108 microm. At 4 weeks after injection, the median excess FTH was 59 microm and the median improvement in BCVA was nine letters. At 6 weeks after injection, four of the five patients showed improvement in excess FTH (median 74 microm; 31% reduction from baseline, p = 0.0625) and four of the five showed improvement in BCVA (median improvement of three letters). A single intravitreal injection of 4.0 mg of VEGF Trap-Eye was well tolerated and preliminary evidence of bioactivity was detected. These findings support additional studies investigating multiple injections of VEGF Trap-Eye in patients with DMO.
    The British journal of ophthalmology 02/2009; 93(2):144-9. · 2.92 Impact Factor