Table 2.
Trials in gene therapy for age-related macular degeneration (AMD)
| Trial | Vector | Mechanism | Result |
|---|---|---|---|
| Intravitreal AdGVPDEF.11D | n E1-, partial E3-, E4- deleted adenoviral expressing human PEDF (AdPEDF.11) | PEDF expression with antiangiogenesis | No serious adverse events. Twenty-five patients showed mild transient intraocular inflammation. Limitations include a lack of control group and a small sample size |
| Subretinal rAAV. sFLT-1 Phase 1/IIA | Subretinally administered recombinant AAV (rAAV) with soluble fms-like tyrosine kinase-1 (sFLT-1) | Cellular expression of VEGF binding receptor FLT1 | No serious adverse events. Transient intraocular inflammation in 10%. No difference after removing outliers. |
| Intravitreal AAV2-sFLT01 (Phase 1) | Fusion protein of the sFLT-1 domain 2 with the Fc domain of IgG1 | Cellular expression of VEGF binding receptor FLT1 | No reported immunogenicity. No consistent response |
| RetinoStat (Phase 1) | Expression of angiostatin and endostatin by subretinal injection of equine infectious anemia lentivirus (EIAV-LV) | Antiangiogenesis | No adverse effects related to the lentivirus vector. Fluorescein angiography showed a reduction in the leakage in 71% of the patients, but significant reduction in intraretinal/subretinal fluid compared to the baseline was seen only in one patient. |
| Subretinal AAV-8-based anti-VEGF (RGX-314) (Phase 1/2a) | Nonreplicating, recombinant AAV serotype 8 (AAV8) vector encoding for a soluble anti-VEGF Fab | Binds to RPE cells to produce a therapeutic anti-VEGF protein. | Ongoing At 12 months-maintenance in vision (median of +5 letters) and anatomy (mean CRT reduction of 39 µm) despite a few to no rescue injections. |
| Hemera Biosciences (HMR59) | Intravitreal AAV2-CD59 | Transduces normal retinal cells to increase the expression of a soluble form of CD59 (inhibitor of MAC formation) | Ongoing |
| FOCUS trial-GT005 (Phase 1) | GT005-A recombinant nonreplicating adeno-associated viral (AAV) vector encoding a human complement factor | Targets complement activation | Ongoing |
| OPTIC trial- ADVM-022 (Phase 1) | Intravitreal AAV2.7m8 capsid expressing of the aflibercept protein | Antiangiogenesis | Ongoing 24-week data showed a good safety profile and efficacy |