Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial

The Lancet

Volumn 386, Issue 10011, 2015, Pages 2395-2403

  Rakoczy, Elizabeth P ^a,c   Lai, Chooi May ^a,c   Magno, Aaron L ^c   Wikstrom, Matthew E ^a,c   French, Martyn A ^b   Pierce, Cora M ^c   Schwartz, Steven D ^d   Blumenkranz, Mark S ^e   Chalberg, Thomas W ^f,g   Degli Esposti, Mariapia A ^a,c   Constable, Ian J ^a,c  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^c LIONS EYE INSTITUTE   (Australia)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e STANFORD UNIVERSITY   (United States)

^f Avalanche Biotechnologies   (United States)

^g SIR CHARLES GAIRDNER HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

AGENTS ACTING ON THE EYE; CHLORAMPHENICOL; GAMMA INTERFERON; NEUTRALIZING ANTIBODY; PARVOVIRUS VECTOR; PHENYLEPHRINE; PREDNISOLONE; RANIBIZUMAB; SOLUBLE VASCULOTROPIN RECEPTOR 1; UNCLASSIFIED DRUG; VASCULOTROPIN INHIBITOR; ANGIOGENESIS INHIBITOR; FLT1 PROTEIN, HUMAN; RECOMBINANT PROTEIN; VASCULOTROPIN RECEPTOR 1;

ADENO ASSOCIATED VIRUS; AGE RELATED MACULAR DEGENERATION; AGED; ARTICLE; BEST CORRECTED VISUAL ACUITY; CARDIOVASCULAR DISEASE; CLINICAL ARTICLE; CLINICAL ASSESSMENT; CLINICAL LABORATORY; CONJUNCTIVAL HEMORRHAGE; CONTROLLED STUDY; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; FEMALE; FLUORESCENCE ANGIOGRAPHY; FOLLOW UP; GENOME ANALYSIS; HUMAN; LOW DRUG DOSE; MALE; NEOVASCULAR AGE RELATED MACULAR DEGENERATION; OPTICAL COHERENCE TOMOGRAPHY; OUTCOME ASSESSMENT; PATIENT SAFETY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL; RETINA HEMORRHAGE; SINUS BRADYCARDIA; SUBRETINAL NEOVASCULARIZATION; SYSTEMIC DISEASE; URINARY TRACT INFECTION; VERY ELDERLY; VIRAL GENE THERAPY; VISUAL ACUITY; ADENOVIRIDAE; ADMINISTRATION AND DOSAGE; ADVERSE EFFECTS; CHOROIDAL NEOVASCULARIZATION; CLINICAL TRIAL; COMPLICATION; GENE THERAPY; GENE VECTOR; INTRAOCULAR DRUG ADMINISTRATION; MULTICENTER STUDY; PATHOPHYSIOLOGY; PROCEDURES; WET MACULAR DEGENERATION;

ADENOVIRIDAE; AGED; AGED, 80 AND OVER; ANGIOGENESIS INHIBITORS; CHOROIDAL NEOVASCULARIZATION; FEMALE; GENETIC THERAPY; GENETIC VECTORS; HUMANS; INJECTIONS, INTRAOCULAR; MALE; RANIBIZUMAB; RECOMBINANT PROTEINS; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1; VISUAL ACUITY; WET MACULAR DEGENERATION;

EID: 84952639507     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(15)00345-1     Document Type: Article

References (53)

1. N Congdon, B O'Colmain, CC Klaver et al. Causes and prevalence of visual impairment among adults in the United States Arch Ophthalmol 122 2004 477 485
2. AN Witmer, GF Vrensen, CJ Van Noorden, RO Schlingemann Vascular endothelial growth factors and angiogenesis in eye disease Prog Retin Eye Res 22 2003 1 29
3. RD Jager, WF Mieler, JW Miller Age-related macular degeneration N Engl J Med 358 2008 2606 2617
4. M Kliffen, HS Sharma, CM Mooy, S Kerkvliet, PT de Jong Increased expression of angiogenic growth factors in age-related maculopathy Br J Ophthalmol 81 1997 154 162
5. PF Lopez, BD Sippy, HM Lambert, AB Thach, DR Hinton Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes Invest Ophthamol Vis Sci 37 1996 855 868
6. L Luo, H Uehara, X Zhang et al. Photoreceptor avascular privilege is shielded by soluble VEGF receptor-1 eLife 2 2013 e00324
7. N Bouck PEDF: anti-angiogenic guardian of ocular function Trends Mol Med 8 2002 330 334
8. K Ohno-Matsui, I Morita, J Tombran-Tink et al. Novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors VEGF and PEDF J Cell Physiol 189 2001 323 333
9. VEGF Inhibition Study (V.I.S.I.O.N.) Clinical Trial Group Year 2 efficacy results of 2 randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration Ophthalmology 113 2005 1508 e1-e25.
10. PK Kaiser, DM Brown, K Zhang et al. Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results Am J Ophthalmol 144 2007 850 857 e4.
11. PJ Rosenfeld, DM Brown, JS Heier et al. Ranibizumab for neovascular age-related macular degeneration N Engl J Med 355 2006 1419 1431
12. U Schmidt-Erfurth, PK Kaiser, JF Korobelnik et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies Ophthalmology 121 2014 193 201
13. FG Holz, W Amoaku, J Donate et al. Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular age-related macular degeneration: the SUSTAIN study Ophthalmology 118 2011 663 671
14. CD Regillo, DM Brown, P Abraham et al. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 1 Am J Ophthalmol 145 2008 239 248 e5.
15. S Rofagha, RB Bhisitkul, DS Boyer, SR Sadda, K Zhang Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON Ophthalmology 120 2013 2292 2299
16. R Silva, R Axer-Siegel, B Eldem et al. The SECURE study Ophthalmology 120 2013 130 139
17. MA Singer, CC Awh, S Sadda et al. HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration Ophthalmology 119 2012 1175 1183
18. AE Fung, GA Lalwani, PJ Rosenfeld et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (lucentis) for neovascular age-related macular degeneration Am J Ophthalmol 143 2007 566 583 e2.
19. S Day, K Acquah, P Mruthyunjaya, DS Grossman, PP Lee, FA Sloan Ocular complications after anti-vascular endothelial growth factor therapy in Medicare patients with age-related macular degeneration Am J Ophthalmol 152 2011 266 272
20. RD Jager, LP Aiello, SC Patel, ET Cunningham Jr Risks of intravitreous injection: a comprehensive review Retina 24 2004 676 698
21. SJ Bakri, DM Moshfeghi, S Francom et al. Intraocular pressure in eyes receiving monthly ranibizumab in 2 pivotal age-related macular degeneration clinical trials Ophthalmology 121 2014 1102 1108
22. R Nuzzi, F Tridico Local and systemic complications after intravitreal administration of anti-vascular endothelial growth factor agents in the treatment of different ocular diseases: a five-year retrospective study Semin Ophthalmol 30 2013 129 135
23. S Pershing, SJ Bakri, DM Moshfeghi Ocular hypertension and intraocular pressure asymmetry after intravitreal injection of anti-vascular endothelial growth factor agents Ophthal Surg Lasers Imaging Retina 44 2013 460 464
24. NM Bressler, DS Boyer, DF Williams et al. Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials Retina 32 2012 1821 1828
25. U Schmidt-Erfurth Clinical safety of ranibizumab in age-related macular degeneration Expert Opin Drug Saf 9 2010 149 165
26. D Levison Medicare payments for drugs used to treat wet age-related macular degeneration. Report No.: OEI-03-10-00360 2012 US Department of Health and Human Services Washington DC
27. SY Cohen, G Mimoun, H Oubraham et al. Changes in visual acuity in patients with wet age-related macular degeneration treated with intravitreal ranibizumab in daily clinical practice: the LUMIERE study Retina 33 2013 474 481
28. NM Holekamp, Y Liu, WS Yeh et al. Clinical utilization of anti-VEGF agents and disease monitoring in neovascular age-related macular degeneration Am J Ophthalmol 157 2014 825 833 e1.
29. JA Sahel, B Roska Gene therapy for blindness Annu Rev Neurosci 36 2013 467 488
30. JWB Bainbridge, AJ Smith, SS Barker et al. Effect of gene therapy on visual function in Leber's congenital amaurosis N Engl J Med 358 2008 2231 2239
31. J Bennett, M Ashtari, J Wellman et al. AAV2 gene therapy readministration in three adults with congenital blindness Sci Transl Med 4 2012 120ra15
32. SG Jacobson, AV Cideciyan, R Ratnakaram et al. Gene therapy for Leber congenital amaurosis caused by rpe65 mutations: safety and efficacy in 15 children and adults followed up to 3 years Arch Ophthalmol 130 2012 9 24
33. RE MacLaren, M Groppe, AR Barnard et al. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial Lancet 383 2014 1129 1137
34. RL Kendall, KA Thomas Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor Proc Natl Acad Sci USA 90 1993 10705 10709
35. M Lukason, E DuFresne, H Rubin et al. Inhibition of choroidal neovascularization in a nonhuman primate model by intravitreal administration of an AAV2 vector expressing a novel anti-VEGF molecule Mol Ther 19 2011 260 265
36. TK Maclachlan, M Lukason, M Collins et al. Preclinical safety evaluation of AAV2-sFLT01 - a gene therapy for age-related macular degeneration Mol Ther 19 2011 326 334
37. C Lebherz, A Maguire, W Tang, J Bennett, JM Wilson Novel AAV serotypes for improved ocular gene transfer J Gene Med 10 2008 375 382
38. C Lebherz, AM Maguire, A Auricchio et al. Nonhuman primate models for diabetic ocular neovascularization using AAV2-mediated overexpression of vascular endothelial growth factor Diabetes 54 2005 1141 1149
39. N Provost, G Le Meur, M Weber et al. Biodistribution of rAAV vectors following intraocular administration: evidence for the presence and persistence of vector DNA in the optic nerve and in the brain Mol Ther 11 2005 275 283
40. YK Lai, WY Shen, M Brankov, CM Lai, IJ Constable, PE Rakoczy Potential long-term inhibition of ocular neovascularisation by recombinant adeno-associated virus-mediated secretion gene therapy Gene Ther 9 2002 804 813
41. CM Lai, MJ Estcourt, RP Himbeck et al. Preclinical safety evaluation of subretinal AAV2.sFlt-1 in non-human primates Gene Ther 19 2012 999 1009
42. CM Lai, MJ Estcourt, M Wikstrom et al. rAAV.sFLT-1 gene therapy achieves lasting reversal of retinal neovascularization in the absence of a strong immune response to the viral vector Invest Ophthalmol Vis Sci 50 2009 4279 4287
43. C-M Lai, W-Y Shen, M Brankov et al. Long-term evaluation of AAV-mediated sFlt-1 gene therapy for ocular neovascularization in mice and monkeys Mol Ther 12 2005 659 668
44. M Ritter, J Elledge, C Simader et al. Evaluation of optical coherence tomography findings in age-related macular degeneration: a reproducibility study of two independent reading centres Br J Ophthalmol 95 2011 381 385
45. CC Czerkinsky Nilsson L-Å H Nygren Ouchterlony Ö A Tarkowski A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells J Immunol Meth 65 1983 109 121
46. U Chakravarthy, SP Harding, CA Rogers et al. Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial Lancet 382 2013 1258 1267
47. JE Grunwald, E Daniel, J Huang et al. Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials Ophthalmology 121 2014 150 161
48. Sadda S, Tuomi LL, Ding B, Hopkins JF. Development of atrophy in neovascular AMD treated with anti-VEGF therapy: results of the HARBOR study. Chicago, IL: American Academy of Ophthalmology Annual Meeting, 2014.
49. DF Martin, MG Maguire, SL Fine et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results Ophthalmology 119 2012 1388 1398
50. R Sophie, J Wang, PA Campochiaro, Re Grunwald et al. Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials (Ophthalmology 2014; 121: 150-61) Ophthalmology 121 2014 e34
51. JE Grunwald, M Pistilli, G-S Ying, MG Maguire, E Daniel, DF Martin Growth of geographic atrophy in the comparison of age-related macular degeneration treatments trials Ophthalmology 122 2015 809 816
52. R Channa, R Sophie, S Bagheri et al. Regression of choroidal neovascularization results in macular atrophy in anti-vascular endothelial growth factor-treated eyes Am J Ophthalmol 159 2015 9 19 e2.
53. PA Campochiaro, QD Nguyen, SM Shah et al. Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: results of a phase I clinical trial Hum Gene Ther 17 2006 167 176