Dr. Kiss said that overcoming limitations of gene therapy trials may be as simple as developing or manufacturing a virus that can be delivered intravitreally that can transect the retina.
Adverum has accomplished that with AAC.7m8, Dr. Kiss said. This vector can be delivered via an intravitreal injection and has an apparent higher expression compared to AAV2 and other traditional vectors.
In 2016, the company presented preclinical data from ADVM-022 (AAV.7m8-aflibercept) and ADVM-032 (AAV.7m8-ranibizumab) for the treatment of neovascular AMD. Administered through a single, intravitreal injection, ADVM-022 and ADVM-032 demonstrated compelling proof-of-concept of these vectors’ anti-angiogenic effect, which was comparable to the standard-of-care anti-VEGF therapies in a laser-induced, choroidal neovascularization model of neovascular AMD in non-human primates.
“In that model, the vector behaves very similarly to native aflibercept,” Dr. Kiss said. “Not only that, but in 14 eyes out to 7 months–and in 2 eyes out to 1 year–we can still detect the aflibercept that is being made by this vector, and there may be enough aflibercept to have clinical efficacy.”
Gene therapy is here to stay, Dr. Kiss said.
“Hopefully, it is here sooner rather than later for macular degeneration,” Dr. Kiss explained. “Early studies show that it’s safe whether you go intravitreally or subretinal. It may just be that we’re using the wrong vector and it may be that we’re delivering the wrong molecule. With the delivery of ranibizumab and aflibercept, we may be looming into the era of anti-VEGF gene therapy for AMD.”
1. Heier JS, Kherani S, Desai S, et al. Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial. The Lancet 2017;390:50-61.