Three-Year Follow-Up of Phase 1 and 2a rAAV.sFLT-1 Subretinal Gene Therapy Trials for Exudative Age-Related Macular Degeneration

Rakoczy, Elizabeth; Magno, Aaron L.; Lai, Chooi-May; Pierce, Cora M.; Degli-Esposti, Mariapia A.; Blumenkranz, Mark S.; Constable, Ian J.

doi:10.1016/j.ajo.2019.03.006

Cited by 58 publications

(42 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the first Phase 1 study, gene therapy was reported to be safe and well-tolerated. All patients received ranibizumab injections at baseline and in week 4 [109]. A week after the first injection, the patients in the gene therapy group received subretinal injection of 100 µL of the AAV2 with a dose 1 × 10 10 vg or 1 × 10 11 vg.…”

Section: Sflt-1mentioning

confidence: 99%

Viral-Vector-Delivered Anti-Angiogenic Therapies to the Eye

et al. 2021

View full text Add to dashboard Cite

Pathological vessel growth harms vision and may finally lead to vision loss. Anti-angiogenic gene therapy with viral vectors for ocular neovascularization has shown great promise in preclinical studies. Most of the studies have been conducted with different adeno-associated serotype vectors. In addition, adeno- and lentivirus vectors have been used. Therapy has been targeted towards blocking vascular endothelial growth factors or other pro-angiogenic factors. Clinical trials of intraocular gene therapy for neovascularization have shown the treatment to be safe without severe adverse events or systemic effects. Nevertheless, clinical studies have not proceeded further than Phase 2 trials.

show abstract

Section: Sflt-1mentioning

confidence: 99%

Viral-Vector-Delivered Anti-Angiogenic Therapies to the Eye

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Trials of gene-based delivery of anti-VEGF proteins for neovascular AMD are still in their infancy, although the early data look promising and these treatments could represent a highly durable therapeutic option 31. Regenxbio has announced interim phase I data on the use of RGX-314 for the treatment of neovascular AMD via subretinal injection with durability of protein expression at 6 months,32 and Adverum has announced an investigational new drug application for ADVM-022 delivered by intravitreal injection 33…”

Section: Comparison To Other Extended Dosing Trialsmentioning

confidence: 99%

<p>Brolucizumab: evidence to date in the treatment of neovascular age-related macular degeneration</p>

Yannuzzi¹,

Freund²

2019

OPTH

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is a global health concern and the leading cause of vision loss in the developed world. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the treatment of neovascular AMD, but there are still challenges with delivery of care and treatment burden with currently available medications. Brolucizumab is a single-chain antibody fragment inhibitor of all isoforms of VEGF-A. Its small molecular weight allows for high solubility and tissue penetration. Brolucizumab has most recently been evaluated in 2 parallel phase 3 randomized controlled trials which demonstrated its safety and efficacy in an extended dosing regimen. The present review summarizes the safety, visual and anatomic outcomes, and durability of brolucizumab in the treatment of neovascular AMD and discusses some of the extended dosing regimens explored with currently approved medications and other therapies still under clinical investigation.

show abstract

“…In addition, two other phase 1 trials are currently underway investigating the therapeutic benefits of sFlt-1 gene therapy delivered by intravitreal injection of adeno-associated virus particles [268, 269]. One of them had a one year follow-up report showing decreased center point thickness of 352 µm compared to 552 µm in the control group, as well as increased visual acuity [270]. …”

Section: Clinical Trialsmentioning

confidence: 99%

Gene delivery nanoparticles to modulate angiogenesis

Kim

Mirando

Popel

et al. 2017

Advanced Drug Delivery Reviews

View full text Add to dashboard Cite

Angiogenesis is naturally balanced by many pro- and anti-angiogenic factors while an imbalance of these factors leads to aberrant angiogenesis, which is closely associated with many diseases. Gene therapy has become a promising strategy for the treatment of such a disordered state through the introduction of exogenous nucleic acids that express or silence the target agents, thereby engineering neovascularization in both directions. Numerous non-viral gene delivery nanoparticles have been investigated towards this goal, but their clinical translation has been hampered by issues associated with safety, delivery efficiency, and therapeutic effect. This review summarizes key factors targeted for therapeutic angiogenesis and anti-angiogenesis gene therapy, non-viral nanoparticle-mediated approaches to gene delivery, and recent gene therapy applications in pre-clinical and clinical trials for ischemia, tissue regeneration, cancer, and wet age-related macular degeneration. Enhanced nanoparticle design strategies are also proposed to further improve the efficacy of gene delivery nanoparticles to modulate angiogenesis.

show abstract

Three-Year Follow-Up of Phase 1 and 2a rAAV.sFLT-1 Subretinal Gene Therapy Trials for Exudative Age-Related Macular Degeneration

Cited by 58 publications

References 21 publications

Viral-Vector-Delivered Anti-Angiogenic Therapies to the Eye

Viral-Vector-Delivered Anti-Angiogenic Therapies to the Eye

<p>Brolucizumab: evidence to date in the treatment of neovascular age-related macular degeneration</p>

Gene delivery nanoparticles to modulate angiogenesis

Contact Info

Product

Resources

About